Palladium-Catalyzed Trifluoromethylation of Aryl Chlorides..

When I  was working with one of the leading agrochemicals company, I was using 4-chlorobenzotriflouride as starting material for my two projects (trifluralin and a pyrazole derivative with diflouromethyl substituted phnyl).  I know how difficult is to introduce the triflouromethyl group (use of anhydrous HF to convert CCl3 to CF3) and that is why we got the starting material imported. 

Now, MIT chemists have designed a new way to attach a trifluoromethyl group to certain compounds, which they believe could allow pharmaceutical companies to create and test new drugs much faster and potentially reduce the cost of drug discovery. 

MIT Chemistry Professor Stephen Buchwald, who led the research team, says achieving the synthesis has been a long-standing challenge for chemists. "Some people said it couldn't be done, so that's a good reason to try," says Buchwald, the Camille Dreyfus Professor of Chemistry at MIT.

With the new reaction, the CF₃ group can be added at a much later stage of the overall drug synthesis. The reaction can also be used with a broad range of starting materials, giving drug developers much more flexibility in designing new compounds.  Though many groups are trying, the major challenge has been finding a suitable catalyst  to transfer the CF₃ entity from another source to the carbon ring. 

CF₃^- (trifluoromethyl negative ion) tends to be unstable when detached from other molecules, so the catalyst must act quickly to transfer the CF₃ group before it decomposes. The MIT team chose to use a catalyst built from palladium i.e., BrettPhos (see structure). MIT team is not the first to try palladium catalysis for this reaction, but the key to their success was the use of a ligand (a molecule that binds to the metal to stabilize it and hasten the reaction) called BrettPhos 2-(Dicyclohexylphosphino)-3,6-dimethoxy-2'-4'-6'-tri-i-propyl-1,1'-biphenyl,  which they had previously developed for other purposes. 

During the reaction, a CF₃ group is transferred from a silicon carrier to the palladium, displacing a chlorine atom. Subsequently, the aryl-CF₃ unit is released and the catalytic cycle begins anew. The researchers tried the synthesis with a variety of aryl compounds and achieved yields ranging from 70 to 94 percent of the trifluoromethylated products. 

Researchers conclude that, in its current state the process is too expensive for manufacturing use. For drug discovery, however, it may lower overall costs because it streamlines the entire synthesis process.

"For discovery chemistry, the price of the metal is much less important," says Kinzel....

Ref :  http://www.sciencemag.org/cgi/content/abstract/328/5986/1679

Blueberry consumption is beneficial for hepatic diseases....

We know that blueberry has many chemicals such as anthocyanins, proanthocyanidins, resveratrol, flavonols and tannins and how blueberry inhibit mechanisms of cancer cell development and inflammation in vitro. Similar to red grape, some blueberry species contain in their skins significant levels of resveratrol a phytochemical. 

Now research team led by Ming-Liang Cheng, MD, from Department of Infectious Diseases, Guiyang Medical College, Guiyang,  have found that blueberries could reduce liver indices, serum levels of hyaluronic acid and alanine aminotransferase, and increase levels of superoxide dismutase and decrease levels of malondialdehyde in liver homogenates compared with the model group.  Meanwhile, the stage of hepatic fibrosis was significantly weakened. Blueberries increased the activity of glutathione-S-transferase in liver homogenates and the expression of Nrf2 and Nqo1 compared with the normal group, but there was no significant difference compared with the model group. 

The authors suggest that blueberry consumption is beneficial for hepatic diseases (including fibrosis)....

I read an article in the same lines, where in the  researchers from Miyazaki prefecture of southern Japan and University of Miyazaki, screened nearly 300 different agricultural products for potential compounds that suppress HCV replication and uncovered a strong candidate in the leaves of rabbit-eye blueberry (native to the southeastern US). They purified the compound and identified it as proanthocyandin (a polyphenol similar to the beneficial chemicals found in grapes and wine). While proanthocyandin can be harmful, Kataoka and colleagues noted its effective concentration against HCV was 100 times less than the toxic threshold. The researchers are  hoping to explore the detailed mechanisms of how this chemical stops HCV replication....

Ref :  http://www.biologynews.net/archives/2009/08/07/the_hepatitis_healing_power_of_blueberry_leaves.html

Liquid Crystals - A New Way to Better Data Storage ?

In continuation of my update on liquid crystals (after a long gap)....

As cell phones and computers continue to shrink, many companies are seeking better ways to store hundreds of gigabytes of data in small, low-power devices. A special type of liquid crystal (similar to those used in computer displays and televisions) offers a solution  and lasers can encode data throughout a liquid crystal known as holographic storage, the technique makes it possible to pack much more information in a tiny space.   

But attempts to use liquid crystals for data storage have had limited success. In order to reliably record and rewrite data, researchers must figure out a way to uniformly control the orientation of liquid crystal molecules as the most liquid crystal technologies currently rely on physical or chemical manipulation, such as rubbing in one direction, to align molecules in a preferred direction. 

In an important advance, scientists at the Tokyo Institute of Technology have created a stable, rewritable memory device that exploits a liquid crystal property called the "anchoring transition". Researchers  demonstrated memory and rewritable bistable devices based on an anchoring transition of a nematic liquid crystal on a perfluoropolymer surface. Spontaneous orientation changes between planar and homeotropic occur on cooling and heating with a large temperature hysteresis. Orientation switching also occurs by applying an electric field with a response time of several milliseconds depending on the field strength claims the researchers.

Using either a laser beam or an electric field, the researchers can align rod-like liquid crystal molecules in a polymer. Their tests show that the liquid crystal created by the team can store data, be erased and used again...

"This is the first rewritable memory device utilizing anchoring transition," said Hideo Takezoe, who led the research. And because the device is bi-stable -- the liquid crystals retain their orientation in one of two directions -- it needs no power to keep images, adds Takezoe.

 Ref : http://jap.aip.org/japiau/v107/i12/p123108_s1?isAuthorized=no

Resveratrol in Red Wine Neutralizes Toxicity of Proteins Related to Alzheimer's

We know that, Resveratrol (found in the skin of red grapes and is a constituent of red wine, see structure)  (trans-resveratrol) is a phytoalexin produced naturally by several plants when under attack by pathogens such as bacteria or fungi.  And also it has been reported to possess diverse activities such as, anti-cancer, anti-inflammatory, blood-sugar-lowering and other beneficial cardiovascular effects in mouse and rat models of testings. In the only positive human trial, extremely high doses (3–5 g) of resveratrol in a proprietary formulation have been necessary to significantly lower blood sugar.Claims of anti-aging effects of the same compounds is to be still established.

Now researchers led by Rensselaer Professor Peter M. Tessier, have come up with an interesting finding i.e., resveratrol - has the ability to neutralize the toxic effects of proteins linked to Alzheimer's disease. 

As per the claims by the researchers, resveratrol picks out the clumps of peptides that are bad and leaves alone the ones that are benign, it helps us to think about the structural differences between the peptide isoforms (different packing arrangements of a particular peptide) Deformations of a particular peptide  the Aβ1-42 peptide,   have been linked to Alzheimer's disease. 

Improperly folded peptides have been shown to collect in accumulations called "plaques (often found near areas of cell death in diseased brain)" within the brain.

Researchers conclude that, though it is not clear that resveratrol is able to cross the blood-brain barrier. However, the molecule has garnered interest in recent years for its potential impact on cancer and aging...

Ref : http://www.jbc.org/content/early/2010/05/28/jbc.M110.133108....

New use of old drugs (Metformin & AICAR ) in treating hepatitis C...

In continuation of my update on Metformin...

Researchers from  University of Leeds have found drugs such as antidiabetic  drug  Metformin  (right  structure)  and                AICAR, (5-Amino-4-imidazole carboxamide ribonucleotide) below right structure) used to combat obesity, can prevent the hepatitis C virus from replicating in the body.

Drugs such as Metformin and AICAR work by stimulating an enzyme called AMP kinase (AMPK) which regulates energy within our cells,  the very enzyme that hepatitis C virus represses to enable it to replicate. As per the claim by the researchers, the hepatitis C virus switches off AMPK so that the cell continues production of lipids and membranes, both of which are vital to its survival. 

AMPK's usual function is to conserve the energy balance in cells (it does by temporarily shutting down the production of lipids (fats) and membranes) when it senses an increase in energy requirements. Researchers  claim that, when a cell becomes infected by a virus,  AMPK gets activated and  shuts down certain functions of the cell temporarily until the cell's energy is rebalanced. 

Building on this finding, the research team were able to examine how cells would react when treated with common drugs that stimulate AMPK. They found that in infected cells, the drugs were able to halt virus replication, enabling cells to clear the infection...

"We're very excited about these findings," says Professor Mark Harris from the University's Faculty of Biological Sciences. "These drugs are already on the market, and whilst substantial clinical trials still need to take place before they can be used to treat hepatitis C infection, we think it could be an enormous step forward in the battle against the virus."  ....

Ref : http://www.leeds.ac.uk/news/article/825/new_use_for_old_drugs_in_treating_hepatitis_c?research

Crizotinib Shows Dramatic Results for Shrinking Tumors (lung cancer)....

Patients with a specific kind of lung cancer may benefit from a Phase III clinical trial offered by the Moores UCSD Cancer Center. The new drug, crizotinib (structure), under development by Pfizer, showed dramatic results in reducing lung cancer tumors in some patients during Phase I and II clinical trials.

"The results of the first two trials have been very encouraging," said Lyudmila Bazhenova, MD, assistant clinical professor at UC San Diego School of Medicine and a member of the Moores UCSD Cancer Center...

According to a preliminary study,  57% of patients had their tumors reduced and at eight weeks of the treatment, 87% showed disease stabilization.

The Phase III clinical trial will compare crizotinib with standard-of-care chemotherapy in the treatment of ALK-positive recurrent NSCLC. Through a randomized selection process, patients will either be treated with chemotherapy or crizotinib. If the patients who are given the chemotherapy do not respond to treatment, they will be given crizotinib at the end of the trial....

Ref : http://ucsdnews.ucsd.edu/newsrel/health/06-22ShrinkingTumors.asp

FDA approves Jevtana to treat men with prostate cancer

In continuation of my update on Cabazitaxel......

FDA approves Jevtana to treat men with prostate cancer

Synergistic activity of Sorafenib and Sulforaphane abolishes pancreatic cancer...

In continuation of my update on "Sorafenib", I find this info interesting to share with...

A team led by Professor Dr. Ingrid Herr, Head of the Department of Molecular Oncosurgery, a group of the Department of Surgery at Heidelberg University Hospital, have come up with an interesting finding, i.e.,  Sorafenib  (used for advanced liver and kidney cancer) also appears to be effective against cancer stem cells in pancreatic cancer. It inhibits resistant tumor stem cells and is also especially effective in combination with sulforaphane, an organic compound found in broccoli. 

In their tests on cancer cells and mice, the researchers showed that sorafenib inhibited typical properties of cancer stem cells from pancreas tumors and greatly reduced tumor growth. However, this effect lasted only for a short time and after four weeks, new colonies of cancer stem cells formed that no longer reacted to further treatment with sorafenib. The resistance is probably related to a certain metabolic pathway, the NF-kB pathway, that is activated by sorafenib, claims the researchers. 

Naturally occurring substance(s) e.g., sulforaphane (vegetables from the cruciferous family such as broccoli and cauliflower possess a high content of sulforaphane, an anti-cancer compound)  that block precisely this undesired NF-KB pathway and thus make the dangerous cells vulnerable.  The experiments show that sulforaphane prevents the activation of the NF-kB pathway by sorafenib and hence the combination treatment reinforces the effect of sorafenib without causing additional side effects. Researchers conclude that the invasive potential of cancer cells was prevented  and  metastasis was completely blocked in cell culture experiments. 

"We assume that nutrition may be a suited approach to break therapy resistance of cancer stem cells and thus make tumor treatment more effective," Professor Herr suggested....

Ref : http://cancerres.aacrjournals.org/content/70/12/5004

New evidence that chili pepper ingredient fights fat

In continuation of effect of chilli pepper on obesity.......

New evidence that chili pepper ingredient fights fat

New world Helicobacter pylori genome sequenced, dynamics of inflammation-related genes revealed

In continuation of my update on Helicobacter pylori.......
New world Helicobacter pylori genome sequenced, dynamics of inflammation-related genes revealed

Sulindac inhibits tumor growth !...

We know that, Sulindac(structure), is useful in the treatment of acute or  chronic inflammatory conditions. Sulindac is a prodrug, derived from sulfinylindene, that is converted in the body to the active NSAID. More specifically, the agent is converted by liver enzymes to a sulfide that is excreted in the bile and then reabsorbed from the intestine. This is thought to help maintain constant blood levels with reduced gastrointestinal side effects. Some studies have shown sulindac to be relatively less irritating to the stomach than other NSAID's except for drugs of the COX-2 inhibitor class. The exact mechanism of its NSAID properties is unknown, but it is thought to act on enzymes COX-1 and COX-2, inhibiting prostaglandin synthesis.

Now researchers from Sanford-Burnham Medical Research Institute (Sanford-Burnham) and their colleagues have figured out how  Sulindac, inhibits tumor growth. The study reveals that Sulindac shuts down cancer cell growth and initiates cell death by binding to nuclear receptor RXRα, a protein that receives a signal and carries it into the nucleus to turn genes on or off. 

As per the claim by the researchers, RXRα normally suppresses tumors, but many types of cancer cells produce a truncated form of this nuclear receptor that does just the opposite. This study showed that shortened RXRα enhances tumor growth by stimulating other proteins that help cancer cells survive. Luckily, the researchers also found that Sulindac can be used to combat this deviant RXRα by switching off its pro-survival function and turning on apoptosis, a process that tells cells to self-destruct.  The interesting part of their research lies in the fact that, they were able to overcome the limitation (cardiovascular side effects associated with Sulindac and other NSAIDs), the researchers tweaked Sulindac, creating a new version of the drug now called K-80003 that both decreases negative consequences and increases binding to truncated RXRα..

"Depending on the conditions, the same protein, such as RXRα, can either kill cancer cells or promote their growth," Dr. Zhang said. "The addition of K-80003 shifts that balance by blocking survival pathways and sensitizing cancer cells to triggers of apoptosis."

Ref :  http://www.cell.com/cancer-cell/retrieve/pii/S1535610810001595

The Revolutionary alkaline diet

I am really happy to share an interesting and important article on Alkaline Diet, by Emma Deangela, who has written exclusively for the readers/followers of my blog. I thank Emma for this info, on behalf of  all my blog readers. Its good to see many  authors /writers coming forward to share the knowledge through the social media like facebook/blog/twitter and hope this awareness will help those needy people....

Boost Your Healthy Simply by Alkalizing your Diet!

You've probably heard of alkalizing your body by now and how it will boost your health. But in order to fully appreciate how an alkaline body helps in our daily living, it is imperative to know the components of an alkaline diet and the importance of maintaining the pH of our body.

pH refers to the measure of acidity or basicity of a solution. More accurately, it pertains to the extent of dissociation of hydrogen ions of our body. If we consume the right types and amounts of nutrients and minerals conducive to our body's development, our body is able to maintain the right pH balance. But you may wonder for a moment what exactly are the 'right' nutrients and minerals? This is where alkaline diet comes into the picture.

The concept of alkaline diet is ultimately about foods that leaves an alkaline residue in our body after digestion. Our body's pH balance fluctuates with each intake of food, and in order to maintain it at the optimum pH, our body must have enough alkaline reserves which can only be obtained if we include at the minimum 80% of alkaline foods in our diet.

How do we classify foods into acidic or alkaline foods?

Chlorine, phosphorus and sulfur in food will probably give acidic residue after the food has been digested. Conversely, minerals such as calcium, sodium, magnesium and potassium found in food will leave an alkaline residue.

We should always bear in mind that all foods leave residue in our body after digestion. If you recall the food pyramid taught in Health education classes, meat and seafood, dairy products, alcoholic drinks, chemical sweeteners, sweets and chocolates, and even grains forms acidic residue! However, green leafy vegetables and fruits low in sugar contain organic aids and are full of alkaline goodness after digestion. So do remember to include a larger proportion of greens and fruits in your diet to maintain an alkaline pH in your body.

Why is it Important to Alkalize the Body?

People living in the modern society are plagued with many diseases and the growing number of sufferers far outstripped our ancestors? Why is such a scenario happening? It can be attributed to our diet which is heavily acidic. Foods that leaves a high content of acidic residues revolves in our circulatory system and are not rid of by our kidneys, lungs and bowels.

According to Dr Theodore Baroody, author of the critically acclaimed book "Alkalize or Diet", the reason for these diseases was due to excessive acidic residue in our body. Acidic mediums are conducive for the breeding of diet-related diseases, which will lead to death. When our body is deprived of the essential alkaline reserves, nutrients and minerals, excessive acids in our bloodstream may lead to slow poisoning of our body due to our diet which comprises of a high percentage of acidic foods. Excess acids will also weaken and in severe cases, damage our bodily functions and cellular actives such as respiration, digestion, hormone production and blood circulation.

Start with an Alkaline Diet Today!

If you are guilty of consuming acid-rich food, fret not. You can definitely reverse the situation through alkalizing your body today. We will be able to enjoy a new lease of energy if we maintain the pH balance in our body. On top of that, another benefit of the alkaline diet is to remove the acidic environment that serves as the breeding ground of acidic toxins which will over time result in an onslaught of diseases. Nutritionists and medical doctors recommends a daily consumption of at least five servings of vegetables and green foods which are highly alkaline.

Affluence and technology have resulted in an epidemic of diet-related diseases. However, there is no need to remain pessimistic. Instead of blindness pursuit of wealth and fame, which will come to naught without good health, why not change your health for the better starting today? We should all grab this opportunity and start incorporating the alkaline diet into our everyday life. It may be difficult to give up your favorite acidic foods at the start, but be assured that your efforts will pay off when you see your overall health being restored. Instead of consuming supplements and medicine, start with the root of the problem - diet. And the solution is to begin alkalizing your body by providing an alkaline environment for every cells and bodily functions in your body to thrive.

About the Author –Emma Deangela is one of the key authors for Alkaline Diet.  She loves to share her experience with her readers on tips to stay healthy, disease free, and how to lose weight the alkaline way. Her alkaline diet newsletter is available at Alkaline Diet, so if you would like to find out more about juicy alkaline diet tips and recipes do visit her blog.....

Two-drug phase I trial shows promise in treating late-stage ovarian cancer

In continuation of my update on carboplatin .....

Researchers from Indiana University School of Medicine, have come up  with interesting finding from a two-Drug Phase I Trial Show, i.e.,  the combination of decitabine (see structure) and carboplatin appears to improve the outcome of women who have late-stage ovarian cancer. Researchers report four of 10 patients who participated in a phase I clinical trial had no disease progression after six months of treatment. One patient experienced complete resolution of tumor tissue for a period of time.

"Carboplatin is the most efficient drug therapy for ovarian cancer,"  unfortunately, patients with recurrent disease become resistant to the drug after one or two rounds claims the lead researcher.."

Decitabine was first used to treat the study patients intravenously daily for five days followed on the eighth day with carboplatin. After a month, the regimen begins again.

Encouraged by the results of the phase I trial, which determined the safety of two different dosing regimens, a phase II trial is now under way with 17 patients already enrolled. Phase II trials are primarily focused on assessing the effectiveness of a drug or treatment protocol.

As per the claim by the researcher, decitabine  (a known methylation inhibitor) can help return tumor suppression genes to an active state, and also improve cells' susceptibility to anti-cancer drugs like carboplatin. Researchers adds that decitabine isn't just targeting active ovarian cancer cells, but also cancer stem cells that seem to survive the first treatments. 

Researchers conclude that, by keeping tumor suppression genes from being methylated, carboplatin and other platinum-based treatments for ovarian cancer have a better chance of success in the late stages.

Ref : http://www3.interscience.wiley.com/journal/123500856/abstract?CRETRY=1&SRETRY=0

Eribulin mesylate drug may help extend lives of women with advanced breast cancer..

We know that, Eribulin (see structure E7389) is an investigational  anticancer drug. Eribulin was previously known as E7389.  Eribulin is currently being investigated by Eisai Co. for the third-line treatment of advanced breast cancer in patients who have been previously treated with anthracyclines, taxanes and capecitabine, as well as a variety of other solid tumors, including non-small cell lung cancer, prostate cancer and sarcoma.

Structurally, eribulin is a fully synthetic macrocyclic ketone analogue of the marine sponge natural product halichondrin B a potent mitotic inhibitor with a unique mechanism of action found in the Halichondria genus of sponges. Eribulin is a mechanistically-unique inhibitor of microtubule dynamics, exerting its anticancer effects by triggering apoptosis of cancer cells following prolonged mitotic blockage. A new synthetic route to E7389 was published in 2009.

Now   research team at the University of Leeds and St James's Institute of Oncology led an international trial of the new chemotherapy drug, eribulin mesylate. As per the claim by the researchers, average survival was typically 25 per cent longer for women who took eribulin mesylate.

In the EMBRACE trial, 762 patients with advanced breast cancer received either eribulin or standard cancer treatment. All of the patients had already been heavily treated with conventional therapies, but their disease had returned or spread to other parts of the body.  Researchers concluded that those who took the new drug lived for 13.1 months, on average, compared with 10.7 months for those on conventional chemotherapy. The drug was also well-tolerated by most patients. Researchers hope that these results may establish eribulin as a new, effective treatment for women with late-stage metastatic breast cancer (either single drug or in combination with other anticancer drug). The drug is not yet available for routine clinical treatment and is awaiting regulatory approval in the European Union, the US and Japan.

"Until now, there hasn't really been a standard treatment for women with such advanced breast cancer. For those women who have already received all of the recognised treatments, these are promising results, claims the lead investigator Professor Christopher Twelves...

Ref : http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=74&abstractID=50309

Polyphenols in red wine and green tea halt prostate cancer growth, study suggests

In continuation of my update on Green Tea and EGCG........

"The profound impact that the antioxidants in red wine and green tea have on our bodies is more than anyone would have dreamt just 25 years ago," Weissmann added. "As long as they are taken in moderation, all signs show that red wine and green tea may be ranked among the most potent 'health foods' we know." ....

Polyphenols in red wine and green tea halt prostate cancer growth, study suggests

New evidence that drinking coffee may reduce the risk of diabetes

In continuation of my update on benefits of coffee....

New evidence that drinking coffee may reduce the risk of diabetes

Carbamazepine Reduces Hepatic Fibrosis.....

We know that Carbamazepine (CBZ see structure), is an  anticonvulsant and mood stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia. It is also used off-label for a variety of indications, including attention-deficit hyperactivity disorder (ADHD), schizophrenia, phantom limb syndrome, paroxysmal extreme pain disorder, and post-traumatic stress disorder.

Now researchers from University of Pittsburgh School of Medicine, have come up with interesting finding about this drug, i.e., the liver scarring of α1-antitrypsin (AT) deficiency, the most common genetic cause for which children undergo liver transplantation, might be reversed or prevented with carbamazepine.  The disease, which affects 1 in 3,000 live births, a gene mutation leads to an abnormal protein, dubbed ATZ, that unlike its normal counterpart is prone to aggregation. As per the claim by the researchers these aggregates of ATZ accumulate in the liver cells and eventually lead to scarring, or fibrosis, of the organ and set the stage for tumor development. The disease sometimes doesn't show itself until adulthood, when the liver starts to fail due to cirrhosis or cancer.

Encouraged by the fact that carbamazepine could enhance a natural cellular pathway called autophagy  or self-digestion, researchers thought that  it might be able to rid the cells of the toxic aggregated ATZ. For the study researchers treated an ATZ cell line with carbamazepine. They found that carbamazepine did indeed cause a marked decrease in ATZ because the abnormal proteins were degraded more quickly via autophagy, and so they did another experiment in a mouse model of AT deficiency.

The most amazing finding,  as per the claim by the researchers is  that the drug reversed the fibrosis in the livers of the mice and after two weeks of treatment the liver tissue resembled that of a healthy mouse...

The ability of carbamazepine and drugs like it to "soup up" the cell's autophagy machinery might have value in other disorders ― such as Alzheimer's disease, Huntington's disease and Parkinsonism ― that are thought to be caused by toxic effects of protein clumping in the brain. Dr. Perlmutter and his colleagues are now exploring these possibilities in preclinical studies. ....

Ref : http://www.sciencemag.org/cgi/content/abstract/science.1190354v1

Azithromycin as effective as penicillin for early-stage syphilis...

We know that azithromycin (structure) is one of the world's best-selling  antibiotics. It is derived from erythromycin; however, it differs chemically from erythromycin in that a methyl-substituted nitrogen atom is incorporated into the lactone ring, thus making the lactone ring 15-membered.  Azithromycin is being used to treat or prevent certain bacterial infections, most often those causing middle ear infections, tonsillitis, throat infections, laryngitis, bronchitis, pneumonia, Typhoid, certain urinary tract infections and venereal diseases, such as non-gonococcal urethritis, chlamydia, gonorrhea and cervicitis. and sinusitis. In recent years it has primarily been used to prevent bacterial infections in infants and those with weaker immune systems.

Now researchers lead by Dr. Edward W. Hook, III of University of Alabama at Birmingham have come up with an interesting finding, i.e., antibiotic pills (azithromycin) are as effective as penicillin injections in curing early-stage syphilis in HIV-negative volunteers. 

Although long-acting penicillin delivered by injection is recommended as the preferred treatment for early syphilis, the authors note that this therapy has shortcomings, particularly in resource-limited settings. Penicillin injections can cause allergic reactions, and the drug must be refrigerated and administrated by trained personnel. The orally administered azithromycin may provide a good alternative for treating HIV-negative people with early-stage syphilis, the scientists conclude. They note that there is a potential for syphilis-causing bacteria to acquire resistance to macrolide drugs such as azithromycin and they recommend continued research into this possibility..

Ref : http://www.niaid.nih.gov/news/newsreleases/2010/Pages/syphilis.aspx

Telomeres: Size matters when it comes to DNA

In continuation of my update on Telomerase and Telomerase inhibition....

Telomeres: Size matters when it comes to DNA

Lovastatin: A New Weapon Against Plague?

We know that, Lovastatin is a member of the drug class of statins,  used for lowering  cholesterol (hypolipidemic agent) in those with hypercholesterolemia and so preventing cardiovascular disease. Lovastatin is a naturally occurring drug found in food such as oyster mushrooms  and red yeast rice.

Now scientists at the Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (CNRS/Université Aix-Marseille 2), have found that Lovastatin protects animals against the deadly effects of plague.

After inoculating small rodents with the Yersinia pestis bacterium, the team led by Didier Raoult and Michel Drancourt at the URMITE (CNRS/Université Aix-Marseille 2) showed that animals treated with lovastatin presented fewer and less severe infections. Lovastatin therefore has preventive properties against plague mortality in an animal model. This experimental study also reveals that this statin has no direct antibiotic effect against Yersinia pestis but that it prevents the development of septicemia.  

Researchers conclude that Lovastatin had no in-vitro antibiotic effect against Y. pestis. The difference in the mortality between control mice (11/15; 73.5%) and lovastatin-treated mice (3/15; 20%) was significant (P<0.004; Mantel-Haenszel test). Dead mice exhibited Y. pestis septicemia and inflammatory destruction of lung and spleen tissues not seen in lovastatin-treated surviving mice. These data suggest that lovastatin may help prevent the deadly effects of plague, with a caution that field observations are warranted to assess the role of lovastatin in the prophylaxis of human plague....

Ref : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0010928

FDA accepts Orexigen's Contrave NDA for treatment of obesity

Orexigen Therapeutics, Inc., a biopharmaceutical company focused on the treatment of obesity, recently anounced that the U.S. Food and Drug Administration (FDA) has accepted for filing the Company's New Drug Application (NDA) for Contrave(R) (see structrures below ; naltrexone SR   and bupropion SR), its investigational drug for the treatment of obesity. The NDA is based on a substantial body of evidence gathered through the Contrave Obesity Research (COR) clinical program, which included over 4,500 patients.....

"We are pleased the FDA has accepted our NDA for filing and look forward to working with the Agency during the review process," said Michael Narachi, President and CEO of Orexigen. "If approved, we believe Contrave will become an important therapeutic option for obese patients, making weight loss and weight maintenance an achievable cornerstone in the treatment of obesity and its common co-morbidities."

Ref : http://ir.orexigen.com/phoenix.zhtml?c=207034&p=irol-newsArticle&ID=1432740&highlight=

ACT Biotech's Telatinib receives orphan drug designation from FDA for treatment of gastric cancer

ACT Biotech's Telatinib receives orphan drug designation from FDA for treatment of gastric cancer..

Telatinib (see structure,  source : ChemBlink) :
(17-Demethoxy-17-allylaminogeldanamycin; Tanespimycin; 17-Allylaminogeldanamycin)

Bone drug (Zoledronic acid) suppresses wandering tumor cells in breast cancer patients

In continuation of my update on zoledronic acid, I find this info really  interesting.  Researchers from Washington University School of Medicine in St. Louis, have found that the bone-strengthening drug zoledronic acid (Zometa) can help fight metastatic breast cancer when given before surgery.

When the drug was given along with chemotherapy for three months before breast cancer surgery, it reduced the number of women who had tumor cells in their bone marrow at the time of surgery.

Tumors shed thousands of cells, which spread throughout the body and are referred to as disseminated tumor cells (DTCs). Breast cancer DTCs often lodge in bone marrow where bone growth factors help them survive.

Chemotherapy can increase bone turnover and bone growth factors, potentially exacerbating the problem of DTCs in the bone, which can resurface later to cause metastatic disease in cancer patients.

Researchers believe that zoledronic acid inhibits the release of growth factors that help support the growth of DTCs.

In this randomized phase II clinical trial, researchers split 109 women with newly diagnosed stage II or stage III breast cancer into two groups. The control group received chemotherapy alone, while the other received a combination treatment of chemotherapy and zoledronic acid. After three months of therapy, patients with DTCs in their bone marrow decreased from 43 percent to 30 percent in the combination group, compared with a decrease from 48 percent to 47 percent in the control group. This result approached statistical significance.

Zoledronic acid treatment with chemotherapy had additional benefits. Women in the combination group experienced significant gains in bone density after 12 months. This is helpful for breast cancer patients, who often develop osteoporosis as a side effect of chemotherapy and other breast cancer treatments.  

The study also suggested that zoledronic acid may help fight certain types of breast tumors directly. Aft speculates that the drug may stop the tumor from making its own blood supply, modify the immune system in a way that makes it harder for tumor cells to survive or even cause the cancer cells to commit suicide.....

Ref : http://www.ncbi.nlm.nih.gov/pubmed/20362507?dopt=Abstract

Chili peppers may cause weight loss and fight fat buildup, says study

In one of my earlier blog article, titled "Peppers may increase energy expenditure in people tying to lose weight"....have mentioned that researchers form UCLA's Center for Human Nutrition in Los Angeles, CA, lead by Dr. David Heber claimed that "peppers may increase energy expenditure in people tying to lose weight". 

Now interestingly, Steven C. Powell, has come up with new evidence that capsaicin (see below structure), the stuff that gives chili peppers their kick, may cause weight loss and fight fat buildup by triggering certain beneficial protein changes in the body. Their study, which could lead to new treatments for obesity, appears in ACS' monthly Journal of Proteome Research........details ...

Ref : Chili peppers may cause weight loss and fight fat buildup, says study  

RADIANT-3 study results show everolimus significantly extends progression-free survival in patients with advanced pancreatic neuroendocrine tumors...

We know that Everolimus (RAD-001, marketed by Novartis under the  tradenames Zortress (USA) and Certican (Europe and other countries) in transplantation medicine and Afinitor in oncology) is the 42-O-(2-hydroxyethyl) derivative of sirolimus and works similarly to sirolimus as an mTOR (mammalian target of rapamycin) inhibitor. It is currently used as an immunosuppressant to prevent rejection of organ transplants. Much research has also been conducted on everolimus and other mTOR inhibitors for use in a number of cancers.

The FDA has approved everolimus for the treatment of advanced kidney cancer on March 30, 2009 and for organ rejection prophylaxis on April 22, 2010. Now Novartis Pharmaceuticals Corporation announced that the  Phase III study of Afinitor® (everolimus, see structure) tablets plus best supportive care met its primary endpoint, showing the drug significantly extended progression-free survival, or time without tumor growth, in patients with advanced pancreatic neuroendocrine tumors (NET). The study, RADIANT-3 (RAD001 In Advanced Neuroendocrine Tumors), is part of the largest clinical trial program of its kind. 

Everolimus is approved under the trade name Afinitor® (everolimus) tablets for the treatment of patients with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib.  

As  per the claim by   Herve Hoppenot, President, Novartis Oncology, Everolimus was developed to inhibit the mTOR protein, which is a critical target in treating various cancers, including NET. Results from RADIANT-3 demonstrate that everolimus has the potential to become an important treatment option for patients with advanced pancreatic NET, where there is a major unmet need.

"These study results will serve as the basis of worldwide regulatory filings for everolimus and bring us one step closer to our goal of offering these patients a new therapy."...says Herve Hoppenot...

Ref : http://www.novartis.com/newsroom/media-releases/en/2010/1421290.shtml

Synthetic peptide may regenerate brain tissue in stroke victims

A synthetic version of a naturally occurring peptide promoted the   creation of new blood vessels and repaired damaged nerve cells in lab animals, according to researchers lead by Dr. Daniel Morris Sr.Staff Physician at Henry Ford Hospital in Detroit.

"Neurorestorative therapy is the next frontier in the treatment of stroke." claims Dr. Daniel Morris...

As per the claim by the researchers,  addition of  the synthetic peptide Thymosin beta 4 (structure : acetate of Thymosin beta 4 : courtesy : ChemBlink) to a group of drug treatments including statins (used for neurorestorative therapy to activate repair mechanisms) repaired and regenerated stroke-injured brain tissue.

Interestingly, this  research follows an earlier study reported by the same team in March, which found that Thymosin beta 4 improved neurological function after stroke in adult rats by increasing the formation of protective myelin around nerve fibers in brain cells.

In the latest study, adult rats were dosed with Thymosin beta 4 one day after they were subjected to a blockage in the cerebral artery, then given four more doses, once every three days. Rats treated only with saline were used as a control group. After eight weeks, the Thymosin beta 4 group showed significant overall improvement compared to the control group.

The researchers concluded that the peptide improved blood vessel density as well as promoted a certain type of immature brain cells called oligodendrocyte progenitor cells to differentiate into mature oligodendrocytes, which produces myelin to protect axons in nerve cells.

These experiments conclude that the peptide repairs and regenerates stroke-injured brain tissue. and as per the claim by the researchers,  the results of the first study also were similar to other research using the peptide to regenerate damaged heart, corneal tissue and wound repair...

Ref : http://www.henryfordhealth.org/body.cfm?id=46335&action=detail&ref=1107

Body's own proteins may lead the way in global fight against tuberculosis

Body's own proteins may lead the way in global fight against tuberculosis

Bafetinib demonstrates significant inhibition of glioblastoma multiforme cell lines (preclinical trials)..

The treatment of chronic myeloid leukemia (CML)  changed  dramatically with the emergence of the ABL tyrosine kinase inhibitor (TKI) imatinib mesilate. However, primary and secondary imatinib resistance has been frequently reported, particularly in patients with advanced-stage disease. To override imatinib resistance, three second-generation ABL TKIs, i.e., dasatinib, nilotinib and bosutinib, were developed. Bafetinib (see structure source : Chemblink :INNO-406, NS-187) is a dual ABL/Lyn inhibitor developed by the team at Kyoto University Hospital in collaboration with Nippon Shinyaku. 

Bafetinib was 25-55 times more potent than imatinib in blocking BCR/ABL autophosphorylation, while otherwise retaining specificity for ABL and Lyn. Bafetinib had antiproliferative effects against cells bearing wild-type or most mutated BCR/ABL proteins, except T315I, and also inhibited BCR/ABL-positive leukemic cell growth in the central nervous system. A phase I study on bafetinib was completed and the agent was well tolerated and demonstrated clinical activity across a range of doses. Responses occurred even in the setting of a heavily pretreated population, thus making bafetinib a viable option for CML therapy.

Recently  CytRx Corporation, announced that its drug candidate bafetinib (formerly known as INNO-406) demonstrated statistically significant inhibition of glioblastoma multiforme cell lines in a preclinical trial. The company believe that bafetinib could be efficacious in several hematological cancers and  it is  preparing to begin evaluating bafetinib in a Phase 2 proof-of-concept clinical trial in high-risk B-cell chronic lymphocytic leukemia (B-CLL) this quarter, as well as a Phase 2 clinical trial in advanced prostate cancer next quarter.... 

Ref : http://www.cytrx.com/inno_406.html

Promising treatment for aggressive lymphoma identified in new study

In continuation of my update on Lenalidomide... I found this info interesting to share with...

Promising treatment for aggressive lymphoma identified in new study