Cancer treatment revolution potential with new drug

A new study at the University of Warwick, published today in the journal Angewandte Chemie International Edition, has developed a new drug that can manipulate the body's natural signalling and energy systems, allowing the body to attack and shut down cancerous cells.

Called ZL105, the drug is a compound based on the precious metal iridium (organoiridium(III) complex [(η⁵-Cp^xbiph)Ir(phpy)(Cl)]). The study has found ZL105 could potentially replace currently used anticancer drugs, which become less effective over time, cause a wide-range of side-effects and damage healthy cells as well as cancerous.

Commenting on the breakthrough, University of Warwick researcher and study co-author Dr Isolda Romero-Canelon said "The energy-producing machinery in cancer cells works to the limit as it attempts to keep up with quick proliferation and invasion. This makes cancer cells susceptible to minor changes in the cell 'power-house'. Our drug pushes cancer cells over the limit causing them to slow and shut down, whilst normal cells can cope with its effects."

Preliminary data indicate that the novel drug may be ten times more effective in treating ovarian, colon, melanoma, renal, and some breast cancers, according to data obtained by the US National Cancer Institute. The researchers now aim to expand the study to cancers that are inherently resistant to existing drugs and to those which have developed resistance after a first round of chemotherapy treatments.

Study co-author Professor Peter J. Sadler said "Existing cancer treatments often become less effective after the first course, as cancer cells learn how they are being attacked. The drug we have developed is a catalyst and is active at low doses. It can attack cancer cells in multiple ways at the same time, so the cancer is less able to adapt to the treatment. This means the new drugs could be much more effective than existing treatments."

"Platinum-based drugs are used in nearly 50% of all chemotherapeutic regimens, exert their activity by damaging DNA and cannot select between cancerous and non-cancerous cells, leading to a wide-range of side-effects from renal failure to neurotoxicity, ototoxicity, nausea and vomiting.

"In contrast, the new iridium-based drug is specifically designed not to attack DNA, but to have a novel mechanism of action, meaning that it could not only dramatically slow down and halt cancer growth, but also significantly reduce the side effects suffered by
patients" argues Professor Sadler.

This research could also lead to substantial improvements in cancer survival rates. "Current statistics indicate that one in every three people will develop some kind of cancer during their life time, moreover approximately one woman dies of ovarian cancer every two hours in the UK according to Cancer Research UK .It is clear that a new generation of drugs is necessary to save more lives and our research points to a highly effective way of defeating cancerous cells" said Dr Romero-Canelon.

Cancer treatment revolution potential with new drug

Researchers develop potentially safer and more cost-effective therapeutics against West Nile virus

An international research group led by Arizona State University professor Qiang "Shawn" Chen has developed a new generation of potentially safer and more cost-effective therapeutics against West Nile virus and other pathogens.

The therapeutics, known as monoclonal antibodies (MAbs), and their derivatives were shown to neutralize and protect mice against a lethal dose challenge of West Nile virus - even as late as four days after the initial infection.

"The overarching goal of our research is to create an innovative, yet sustainable and accessible low-cost solution to combat the global threat of West Nile virus," said Chen, a researcher at Arizona State University's Biodesign Institute.

West Nile virus is spread by infected mosquitoes, and targets the central nervous system. It can be a serious, life-altering and even fatal disease, and currently, there is no cure or drug treatment against West Nile virus, which has been widely spread across the U.S., Canada, Latin America and the Caribbean.

"The goal of this latest research was twofold," said Chen. "First, we wanted to show proof-of-concept, demonstrating that tobacco plants can be used to manufacture large and complex MAb-based therapeutics. Second, we've wanted to improve the delivery of the therapeutic into the brain to combat West Nile virus at the place where it does the greatest harm."

More...

Researchers develop potentially safer and more cost-effective therapeutics against West Nile virus

Old FDA-approved drugs may hold promise for treatment of rare, drug-resistant cancer

After studying how samples of GIST responded to various concentrations of the 89 drugs in the laboratory, Dr. Duensing and her colleagues identified 37 compounds that showed some anticancer activity in at least one of the concentrations tested. Importantly, they noted that the most promising candidates all belonged to only two major drug classes: inhibitors of gene transcription and so-called topoisomerase II inhibitors. Based on these findings, the research team selected the two most promising compounds for further testing - gene transcription inhibitor mithramycin A (left structure below) , which is in clinical trials to treat Ewing sarcoma, and topoisomerase II inhibitor mitoxantrone (beow right structure), which is used in metastatic breast cancer and leukemia.

Both drugs were highly effective in fighting GIST in laboratory tests. Moreover, the mechanism of action of each drug was linked to the specific underlying biology of these tumors.

"These are very encouraging results," said Dr. Duensing. "The next step will be moving our findings to clinical exploration to see if the results we found in the lab hold up in patients."

Old FDA-approved drugs may hold promise for treatment of rare, drug-resistant cancer

Ref : http://www.upmc.com/media/NewsReleases/2014/Pages/upci-scientists-detect-therapy-for-drug-resistant-cancer.aspx

FDA-approved drug pregabalin effectively treats RLS symptoms with less side effects

In continuation of my update on pregabalin

A report in the Feb. 13 New England Journal of Medicine confirms previous studies suggesting that long-term treatment with the type of drugs commonly prescribed to treat restless leg syndrome (RLS) can cause a serious worsening of the condition in some patients. The year-long study from a multi-institutional research team found that pregabalin - which is FDA-approved to treat nerve pain, seizures, and other conditions - was effective in reducing RLS symptoms and was much less likely to cause symptom worsening than pramipexole, one of several drugs that activate the dopamine neurotransmission system and are FDA approved for treatment of RLS.

"Our key finding is that dopaminergic drugs, while very effective for many people with RLS, can worsen symptoms in some patients over time, while non-dopaminergic pregabalin is not associated with this disturbing side effect," says John Winkelman, MD, PhD, of the Massachusetts General Hospital Department of Psychiatry, senior author of the study. "Those treating RLS patients with dopaminergic drugs need to be aware of this common complication and exercise caution if their symptoms worsen."

FDA-approved drug pregabalin effectively treats RLS symptoms with less side effects

Supramolecular high-aspect ratio assemblies with strong antifungal activity : Nature Communications : Nature Publishing Group

Efficient and pathogen-specific antifungal agents are required to mitigate drug resistance problems. Here we present cationic small molecules that exhibit excellent microbial selectivity with minimal host toxicity. Unlike typical cationic polymers possessing molecular weight distributions, these compounds have an absolute molecular weight aiding in isolation and characterization. However, their specific molecular recognition motif (terephthalamide-bisurea) facilitates spontaneous supramolecular self-assembly manifesting in several polymer-like properties. Computational modelling of the terephthalamide-bisurea structures predicts zig-zag or bent arrangements where distal benzyl urea groups stabilize the high-aspect ratio aqueous supramolecular assemblies. These nanostructures are confirmed by transmission electron microscopy and atomic force microscopy. Antifungal activity against drug-sensitive and drug-resistant strains with in vitro and in vivo biocompatibility is observed. Additionally, despite repeated sub-lethal exposures, drug resistance is not induced. Comparison with clinically used amphotericin B shows similar antifungal behaviour without any significant toxicity in a C. albicansbiofilm-induced mouse keratitis model.

Supramolecular high-aspect ratio assemblies with strong antifungal activity : Nature Communications : Nature Publishing Group

Bitter melon extract may have potential to fight head, neck cancer

Extract taken from an Asian vegetable may have therapeutic qualities to treat head and neck cancer, a Saint Louis University researcher has found. Preliminary findings of the research were published in the Public Library of Science One Journal by Ratna Ray, Ph.D. associate professor of pathology at Saint Louis University. Ray found that bitter melon extract, a vegetable commonly used in Indian and Chinese diets, reduces the head and neck cancer cell growth in the animal model.

"We wanted to see the effect of the bitter melon extract treatment on different types of cancer using different model systems," said Ray, who first tested the extract in breast and prostate cancer cells. "In this study, the bitter melon extract treatment suppressed the head and neck cancer cell growth in the mouse model, reducing the growth of the tumor."

In a controlled lab setting, Ray found that bitter melon extract regulated several pathways that helped reduce the head and neck cancer cell growth in the animal model. After a period of four weeks, Ray found that the growth and volume of the tumor had reduced.

Bitter melon is a tropical vegetable that is commonly used in Indian and Chinese cooking. Ray, who is originally from India, often uses bitter melon in her meals. People in Asia use this vegetable in stir fries, salads, and also drink its juice as part of a healthy diet.

Although more research is needed, Ray believes the bitter melon extract may enhance the current treatment option.

"It's difficult to measure the exact impact of bitter melon extract treatment on the cell growth, but a combination of things -- existing drug therapy along with bitter melon   may help the efficacy of the overall cancer treatment," Ray said.

Head and neck cancers, which account for 6 percent of all cancer cases, start in the mouth, nose, sinuses, voicebox and throat. They frequently are aggressive, and often spread from one part of the head or neck to another.

Before moving to phase I clinical trial with head and neck cancer patients, Ray said she and her team would need to validate their results with other preclinical models.

Ray's initial research found that treatment with this natural substance halted the breast and prostate cancer cell growth, eventually stopping them from spreading.

Ref : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0078006

Bitter melon extract may have potential to fight head, neck cancer

University of Sydney researchers identify new type of medication for osteoporosis

University of Sydney researchers have discovered a new and promising treatment for osteoporosis which is easily delivered in water soluble form. 

After more than four years of investigation, researchers from the Ageing Bone Research Program (Sydney Medical School’s Nepean campus), have found the treatment has shown very promising results in animal experiments. 

The compound is called picolinic acid, a product derived of the essential amino acid tryptophan. 

Lead researcher Professor Gustavo Duque said the odorless compound can be easily dissolved in water. 

“This is a major step in the development of a completely new type of medication for osteoporosis,” he said. 

“Instead of stopping bone destruction, our compound instead stimulates bone formation."

“The product is easily dissolved in water, has a higher level of absorption and did not induce any side effects in the treated mice."

“When this medication was administered in the water of normal and menopausal mice, picolinic acid strongly and safely increased bone mass in normal mice and rescued bone from menopause-associated osteoporosis.”

Professor Duque said the team had patented the compound and will expand their trials to humans in the near future in a bid to address the increasing numbers of people developing the condition. 

“Osteoporosis affects an estimated 300 million people worldwide. One in three women over 50 will experience osteoporotic fractures, as will one in five men."

Ref : http://sydney.edu.au/news/84.html?newscategoryid=1&newsstoryid=12713

University of Sydney researchers identify new type of medication for osteoporosis

Researchers discover new approach to tackle global threat of antibiotic drug resistance

Researchers at McMaster University are addressing the crisis in drug resistance with a novel approach to find new antibiotics.

"We have developed technology to find new antibiotics using laboratory conditions that mimic those of infection in the human body," said Eric Brown, professor in the Department of Biochemistry and Biomedical Sciences.

He is the lead author of the paper published in the online edition of Nature Chemical Biology today. Brown is also a member of the Michael G. DeGroote Institute for Infectious Disease Research (IIDR).

The findings report on the discovery of chemical compounds that block the ability of bacteria to make vitamins and amino acids, processes that are emerging as Achilles' heels for bacteria that infect the human body.

"The approach belies conventional thinking in antibiotic research and development, where researchers typically look for chemicals that block growth in the laboratory under nutrient-rich conditions, where vitamins and amino acids are plentiful," said Brown. "But in the human body these substances are in surprisingly short supply and the bacteria are forced to make these and other building blocks from scratch."

Brown's research group targeted these processes looking for chemicals that blocked the growth of bacteria under nutrient-limited conditions.

"We threw away chemicals that blocked growth in conventional nutrient-rich conditions and focused instead on those that were only active in nutrient-poor conditions," he said.

"We're taking fresh aim at bacterial vitamin and amino acid production and finding completely novel antibacterial compounds."

The approach and the new leads discovered by Brown's lab have potential to provide much-needed therapies to address the growing global threat of antibiotic drug resistance.

"When it comes to this kind of new drug discovery technology, Brown's group are fishing in a new pond," said professor Gerry Wright, director of the IIDR. "These leads have real prospects as an entirely new kind of antibacterial therapy."

Researchers discover new approach to tackle global threat of antibiotic drug resistance

Scientists develop new drug to treat obstructive airway diseases

Scientists have developed a new drug (RPL554, see structure) that could treat obstructive airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) in two ways at once, according to new research published in The Lancet Respiratory Medicine. RPL554 has the potential to both reverse the narrowing of the airways (bronchodilation) and reduce inflammation quicker and with fewer side effects than current therapies.

“Further longer term studies of RPL554 are now eagerly awaited because this could be one of the most substantial advances for some time in the management of patients with chronic airway obstruction”, writes Professor Jadwiga A Wedzicha from University College London, UK, in a linked Comment.

The unique inhaled dual inhibitor—two actions in a single molecule—works by impeding the ability of two enzymes from the phosphodiesterase family (PDE3 and PDE4) to inhibit processes that help relax airway smooth muscle and reduce inflammation.

For the past 40 years, the mainstay of treatment for asthma and COPD (eg, chronic bronchitis and emphysema) has been inhaled anti-inflammatory drugs (corticosteroids) plus bronchodilators (usually long-acting ß2 agonists). But corticosteroids can have substantial side effects, while long-acting ß2 agonists have come under scrutiny for their risk of worsening asthma symptoms. What is more, most people with severe disease and frequent flare-ups fail to achieve good control of symptoms and new treatments are needed. 

Between February, 2009 and January 3013, four small proof-of-concept clinical trials were done in the Netherlands, Italy, and the UK to assess the safety and efficacy of inhaled RPL554 in healthy participants (39 people) and people with mild-to-moderate asthma (28) and COPD (12).

In COPD patients, a single dose of nebulised RPL554 improved respiratory function, producing a 17% increase in FEV1 (forced expiratory volume at 1 second; which measures the volume of air that can be forcibly exhaled in one second after taking a deep breath)—a bronchodilator response at least as effective as the widely use ß2 agonist Salbutamol.

Ref : http://www.thelancet.com/journals/lanres/article/PIIS2213-2600(13)70187-5/fulltext

Scientists develop new drug to treat obstructive airway diseases

Combination of heat, doxorubicin drug and nanotech system may improve ovarian cancer treatment

The combination of heat, chemotherapeutic drugs and an innovative delivery system based on nanotechnology may significantly improve the treatment of ovarian cancerwhile reducing side effects from toxic drugs, researchers at Oregon State University report in a new study.

The findings, so far done only in a laboratory setting, show that this one-two punch of mild hyperthermia and chemotherapy can kill 95 percent of ovarian cancer cells, and scientists say they expect to improve on those results in continued research.

The work is important, they say, because ovarian cancer - one of the leading causes of cancer-related deaths in women - often develops resistance to chemotherapeutic drugs if it returns after an initial remission. It kills more than 150,000 women around the world every year.

"Ovarian cancer is rarely detected early, and because of that chemotherapy is often needed in addition to surgery," said Oleh Taratula, an assistant professor in the OSU College of Pharmacy. "It's essential for the chemotherapy to be as effective as possible the first time it's used, and we believe this new approach should help with that."

It's known that elevated temperatures can help kill cancer cells, but heating just thecancer cells is problematic. The new system incorporates the use of iron oxidenanoparticles that can be coated with a cancer-killing drug and then heated once they are imbedded in the cancer cell.

Other features have also been developed to optimize the new system, in an unusual collaboration between engineers, material science experts and pharmaceutical researchers.

A peptide is used that helps guide the nanoparticle specifically to cancer cells, and the nanoparticle is just the right size - neither too big nor too small - so the immune system will not reject it. A special polyethylene glycol coating further adds to the "stealth" effect of the nanoparticles and keeps them from clumping up. And the interaction between the cancer drug and a polymer on the nanoparticles gets weaker in the acidic environment of cancer cells, aiding release of the drug at the right place.

"The hyperthermia, or heating of cells, is done by subjecting the magnetic nanoparticles to an oscillating, or alternating magnetic field," said Pallavi Dhagat, an associate professor in the OSU School of Electrical Engineering and Computer Science, and co-author on the study. "The nanoparticles absorb energy from the oscillating field and heat up."

The result, in laboratory tests with ovarian cancer cells, was that a modest dose of the chemotherapeutic drug, combined with heating the cells to about 104 degrees, killed almost all the cells and was far more effective than either the drug or heat treatment would have been by itself.

Doxorubicin (see structure), the cancer drug, by itself at the level used in these experiments would leave about 70 percent of the cancer cells alive. With the new approach, only 5 percent were still viable.

The work was published in the International Journal of Pharmaceutics, as a collaboration of researchers in the OSU College of Pharmacy, College of Engineering, and Ocean NanoTech of Springdale, Ark. It was supported by the Medical Research Foundation of Oregon, the PhRMA Foundation and the OSU College of Pharmacy.

Combination of heat, doxorubicin drug and nanotech system may improve ovarian cancer treatment

New type of antibiotic kills multidrug-resistant germ common to health care settings

A new type of antibiotic called a PPMO, which works by blocking genes essential for bacterial reproduction, successfully killed a multidrug-resistant germ common to health care settings, UT Southwestern Medical Center researchers report.

The technology and new approach offer potential promise against the growing problem of antibiotic resistance, the researchers said.

The pathogen (germ) - called Acinetobacter - can cause infections from pneumonia to serious blood or wound infections, posing greater risk to people with weakened immune systems, chronic lung disease, or diabetes, according to the Centers for Disease Control and Prevention (CDC). Acinetobacter infection mainly affects hospitalized patients or those in long-term care facilities, such as those on ventilators or with urinary cathetersor patients treated for open wounds. The CDC considers Acinetobacter, which is resistant to many antibiotics, one of the top bacterial infection threats in the U.S.

In the study in today's Journal of Infectious Diseases, PPMOs  peptide-conjugated phosphorodiamidate morpholino oligomer, (link for PMOs only) designed to combat two strains of Acinetobacter reduced the number of infectious bacteria in mice by more than 90 percent. Survival of infected mice also improved with the treatment. One of the targeted strains was A. baumannii, a dangerous type that accounts for about 80 percent of reported Acinetobacter infections, according to the CDC.

"We set out to target specific genes in Acinetobacter in an effort to inhibit the bacterium-s growth," said Dr. David Greenberg, assistant professor of internal medicine and microbiology and senior author of the study. "With infections from drug-resistant pathogens rising rapidly, there is an urgent need to come up with new approaches such as the use of PPMOs to spur antibiotic development."

The technology that created the synthetic PPMO could be used to develop similar antibiotics targeting other bacteria and viruses, he added.

"We believe there is a lot of promise in developing new antibiotics that target specific pathogens as opposed to so-called broad-spectrum antibiotics that target whole classes of bacteria," said Dr. Greenberg.

New type of antibiotic kills multidrug-resistant germ common to health care settings

Two drugs in combination improve survival in patients with advanced pancreatic cancer

In continuation of my update on nab-paclitaxel (stands for nab-nanoparticle albumin-bound) and gemcitabine...

Investigators at the Vall d´Hebron University Hospital and the Vall d'Hebron Institute of Oncology (VHIO), have participated in an international phase III study, published in The New England Journal of Medicine. Results show that administering these two drugs in combination significantly improves one- and two-year survival in patients with advanced pancreatic cancer versus gemcitabine alone, the first-line treatment or most standard approach for this type of cancer to date.

The new drug is set to become a reference in advanced pancreatic cancer treatment. A multicentre phase III study, with centers participating from 11 countries in North America, Europe and Australia, shows that the drug combination nab-paclitaxel and gemcitabine is more effective in the treatment of patients with advanced pancreatic cancer than gemcitabine alone, which has been the standard treatment for these patients up until now.

The clinical trial, sponsored by Celgene Corporation, involved 861 patients, half of whom were administered the nab-paclitaxel/gemcitabine combination, while the other half received gemcitabine alone. Median overall survival was 8.5 months for nab-paclitaxel/gemcitabine versus 6.7 months for gemcitabine alone. One-year survival rates were 35% and 22%, respectively, and two-year survival rates were 9% and 4%, respectively. Similar side effects were found in the new drug and gemcitabine alike. The trial report therefore concluded that the nab-paclitaxel/gemcitabine combination significantly improves overall survival and response rate in patients with advanced pancreatic cancer.

Two drugs in combination improve survival in patients with advanced pancreatic cancer

Investigational oral regimen for hepatitis C shows promise

In a study of an all-oral drug regimen, a majority of volunteers with liver damage due to hepatitis C virus (HCV) infection were cured following a six-month course of therapy that combined an experimental drug, sofosbuvir, with the licensed antiviral drug ribavirin. The results showed that the regimen was highly effective in clearing the virus and well tolerated in a group of patients who historically have had unfavorable prognoses.

Investigational oral regimen for hepatitis C shows promise

New role for Tamoxifen in saving high-risk breast cancer patients

In continuation of my update on Tamoxifen...

New role for Tamoxifen in saving high-risk breast cancer patients

Ref : http://jco.ascopubs.org/content/early/2013/08/05/JCO.2012.47.8313

Scientists ID compounds that target amyloid fibrils in Alzheimer's, other brain diseases

The UCLA researchers, led by David Eisenberg, director of the UCLA-Department of Energy Institute of Genomics and Proteomics and a Howard Hughes Medical Institute investigator, report the first application of this technique in the search for molecular compounds that bind to and inhibit the activity of the amyloid-beta protein responsible for forming dangerous plaques in the brain of patients with Alzheimer's and other degenerative diseases.

o identify natural and synthetic compounds that might prevent the aggregation and toxicity of amyloid fibrils. Such studies have revealed that polyphenols, naturally occurring compounds found in green tea and in the spice turmeric, can inhibit the formation of amyloid fibrils. In addition, several dyes have been found to reduce amyloid's toxic effects, although significant side effects prevent them from being used as drugs. 

Armed with a precise knowledge of the atomic structure of the amyloid-beta protein, Jiang, Eisenberg and colleagues conducted a computational screening of 18,000 compounds in search of those most likely to bind tightly and effectively to the protein.

Those compounds that showed the strongest potential for binding were then tested for their efficacy in blocking the aggregation of amyloid-beta and for their ability to protect mammalian cells grown in culture from the protein's toxic effects, which in the past has proved very difficult. Ultimately, the researchers identified eight compounds and three compound derivatives that had a significant effect.

While these compounds did not reduce the amount of protein aggregates, they were found to reduce the protein's toxicity and to increase the stability of amyloid fibrils  a finding that lends further evidence to the theory that smaller assemblies of amyloid-beta known as oligomers, and not the fibrils themselves, are the toxic agents responsible for Alzheimer's symptoms.

The researchers hypothesize that by binding snugly to the protein, the compounds they identified may be preventing these smaller oligomers from breaking free of the amyloid-beta fibrils, thus keeping toxicity in check...

Ref : http://elife.elifesciences.org/content/2/e00857

Scientists ID compounds that target amyloid fibrils in Alzheimer's, other brain diseases

Compounds outsmart solid tumors' malfunctioning machinery

In continuation of my update on Rapamycin

"Allosteric regulators are better than proteasome-affecting agents used in clinics because they do not induce classical drug resistance," Dr. Gaczynska said. "They bind to sites on the proteasome molecule used by natural regulatory proteins. They are more specific and are not restricted to proteasome inhibition but can activate the proteasome under certain conditions."

The new strategy was serendipitously found during experiments with rapamycin, a drug that in a highly publicized study by the UT Health Science Center's Barshop Institute for Longevity and Aging Studies was found to extend life span in mice.

Potential

The Molecular Pharmacology report and follow-up studies describe the unexpected and highly desired effects that rapamycin and similar compounds elicit on the proteasome. Based on these studies, it would be possible to design a new line of proteasome regulators with anti-cancer properties, Drs. Osmulski and Gaczynska said.... 

Ref : http://molpharm.aspetjournals.org/content/84/1/104

Compounds outsmart solid tumors' malfunctioning machinery

Multiple sclerosis drug shows promise for preventing heart failure

A drug already approved to treat multiple sclerosis may also hold promise for treating cardiac hypertrophy, or thickening of the cardiac muscle-a disorder that often leads to heart failure, researchers at the University of Illinois at Chicago College of Medicine report. 

Using an experimental mouse model of cardiac hypertrophy, Solaro and his team found that FTY-720 (Fingolimod, see structure) significantly reduced heart mass; lessened fibrosis, or stiffening of the heart muscle; and improved overall cardiac function in the mice that received the drug.

The researchers also showed that the drug inhibits expression of several genes involved in cardiac hypertrophy.

"We saw that FTY-720 blocked the activity of a protein we know is involved in causing heart-cell thickening," said Solaro. When that protein is blocked, he said, collagen and other proteins involved in heart-cell thickening are also down-regulated.

Collagen, a fibrous protein found between heart cells, causes the heart muscle to become stiff. Collagen is often overabundant in people with cardiac hypertrophy.

"When the heart muscle is stiff, it actually takes effort to relax the heart and allow blood to flow into the ventricles, so this is another way this disease causes the heart to work harder than it should have to," Solaro said.

"FTY-720 is a potential therapy to treat this disease and prevent heart failure for people where the disease is acquired through high blood pressure, and possibly inherited hypertrophy as well," he said.

Ref : http://circheartfailure.ahajournals.org/content/6/4/833

Multiple sclerosis drug shows promise for preventing heart failure

Compound Anthracimycin, discovered at sea shows potency against anthrax

Fenical's team in the Scripps Center for Marine Biotechnology and Biomedicine, working in conjunction with San Diego-based Trius Therapeutics, used an analytical technique known as spectroscopy to decipher the unusual structure of a molecule from a microscopic species known as Streptomyces. Initial testing of the compound, which they named anthracimycin, revealed its potency as a killer of anthrax, the infectious disease often feared as a biological weapon, as well as MRSA.

"The real importance of this work is the fact that anthracimycin has a new and unique chemical structure," said Fenical, who added that the finding is a basic research discovery, which could lead to testing and development, and eventually a drug. "The discovery of truly new antibiotic compounds is quite rare. This discovery adds to many previous discoveries that show that marine bacteria are genetically and chemically unique."

The discovery provides the latest evidence that the oceans, and many of its unexplored regions, represent a vast resource for new materials that could one day treat a variety of diseases and illnesses. Fenical, a distinguished professor of oceanography and pharmaceutical science, helped found the field of marine biomedicine as a researcher at Scripps. He is a pioneer in discovering and identifying these novel compounds. His research has helped bring attention to the need for continued exploration of the ocean for science and society....

More at  https://scripps.ucsd.edu/news/13060

Ref : http://onlinelibrary.wiley.com/doi/10.1002/anie.201302749/abstract

Compound discovered at sea shows potency against anthrax

New class of highly potent antimalarial compounds discovered

In a recent work published online today in the journal PNAS, researchers at the Instituto de Medicina Molecular (IMM), in Lisbon, Portugal, have discovered a new class of highly potent antimalarial compounds. These compounds, referred to as Torins, were originally developed by researchers in the Boston, MA to inhibit a key human protein involved in cell growth, mTOR, and have been shown to be effective anticancer agents in rodent models. In research perdormed by Dr. Kirsten Hanson in the laboratory of Dr. Maria Mota, the IMM team and their collaborators have discovered that Torins are extremely effective multistage antimalarials; Torins appear to have a novel activity against the Plasmodium parasites themselves, distinct from both currently used malaria therapeutics and from their ability to target human mTOR.

Torins are capable of killing the cultured blood stages of the human parasite, Plasmodium falciparum, the species which causes most malaria deaths and severe disease, and are equally potent against the liver stages of a model rodent parasite. A single dose of the compound Torin2 delivered at the beginning of the P. berghei liver stage is sufficient to eliminate infection in mice before any Plasmodium parasites reach the blood. "Given the alarming trend of resistance to our current antimalarial therapies, this is really an exciting finding," says Dr. Mota, the senior author of the study, "and we are already working to develop Torin molecules suitable for clinical trials of antimalarial activity in humans."

 Ref : http://www.pnas.org/content/early/2013/07/03/1306097110.full.pdf+html

New class of highly potent antimalarial compounds discovered

Scientists identify promising antiviral compounds

Based on studies of the atomic-level structure of an enzyme that's essential for the maturation of adenovirus and how that enzyme becomes active  conducted at Brookhaven's National Synchrotron Light Source (NSLS) -- we used computational modeling to search for compounds that might interfere with this enzyme and tested the best candidates in the lab."

Out of 140,000 compounds in a national database, the scientists identified two they expect to be able to turn into antiviral agents to combat adenovirus.

This research is a great example of the potential for rational drug design…based on studies of the atomic-level structure of an enzyme…conducted at Brookhaven's National Synchrotron Light Source.

The need for such antiviral compounds stems from the diversity of human adenoviruses and their ubiquitous effects, Mangel said. Adenoviruses cause many types of respiratory diseases (including outbreaks among military recruits), childhood pneumonias, and eye infections -- and may even play a role in obesity. They are particularly dangerous for individuals with impaired immunity, such as transplant recipients and patients with AIDS.

With more than 50 varieties causing this range of diseases, it's unlikely scientists will develop a universally effective vaccine to prevent all strains of adenovirus before infection, Mangel said. But one thing all adenovirus strains share is a common mechanism of making new virus particles once an infection takes root. Targeting that mechanism with antiviral drugs -- the approach taken by the Brookhaven team -- may be a viable way to battle all adenovirus strains.

Mangel worked with fellow Brookhaven scientists William McGrath and Vito Graziano, along with Kathy Zabrocka, a student from Stanford University who was conducting an undergraduate internship in his lab. The research built on work Mangel's lab initiated years earlier to decipher the atomic-level structure of the adenovirus proteinase, an enzyme conserved throughout all strains of the virus that cleaves proteins during the assembly of new virus particles.

"Once those proteins are cleaved, the newly synthesized virus particle is infectious," Mangel explained. "If those proteins are not cleaved, then the infection is aborted. Thus, inhibitors of the adenovirus proteinase should be effective antiviral agents against all strains of adenovirus," he said.

Over several years, Mangel's group found that the activity of the enzyme was highly regulated by two cofactors, a small piece of another adenovirus protein and the viral DNA. Structures of the enzyme alone and in the presence of its cofactors, determined by x-ray crystallography at the NSLS, revealed key regions that could serve as potential targets for blocking the enzyme's activation or protein-cleaving ability.

"All that remained was to find compounds that bind to these targets to prevent the enzyme from functioning," Mangel said.

To find these compounds, the scientists used a technique called DOCKing, which entails computationally probing a region of the protein structure against databases of small molecules to determine which might bind most strongly. Out of a database of 140,000 potential compounds, the scientists identified 30 molecules predicted to fit best and ordered samples to test for inhibitor activity.

Two of the molecules (NSC-36806-left struct;  and NSC37249 right struct) that DOCKing identified turned out to be excellent inhibitors of the adenovirus proteinase. At the concentrations that inhibited the adenovirus proteinase, these same compounds did not inhibit other, similar enzymes. Thus, the compounds appear to be specific inhibitors of the adenovirus enzyme.

Ref : http://www.sciencedirect.com/science/article/pii/S0014579313003876  

The molecules identified are still too large to be delivered as drugs. So the scientists are working to pare down the size in the design of a second-generation compound based upon the binding portions of the two inhibitors. This new molecule is expected to readily enter adenovirus-infected cells and bind even more tightly to the adenovirus proteinase.

"This work should pave the way for the development of effective drugs against all types of adenovirus infections," Mangel said...

Scientists identify promising antiviral compounds