Breaking News
March 22, 2018 - Researchers explain link between 2 key Alzheimer’s proteins
March 22, 2018 - Patients on replacement therapy with thyroid hormone may have more comorbidities
March 22, 2018 - Higher online patient ratings linked to urologists who saw fewer Medicare patients
March 22, 2018 - FDA Approves Ilumya (tildrakizumab-asmn) for the Treatment of Moderate-to-Severe Plaque Psoriasis
March 22, 2018 - Beer Raises Heart Rate; KardiaBand Hyperkalemia Test; CHD Clinics
March 22, 2018 - A retinal implant that is more effective against blindness
March 22, 2018 - New system based on artificial intelligence provides reliable detection of breast cancer
March 22, 2018 - Research offers new understanding about cause of Parkinson’s disease
March 22, 2018 - HORIBA’s Microsemi CRP analyzer improves quality of care in emergency pediatric units, study shows
March 22, 2018 - Range of Vaginal Dryness Products Can Help Postmenopausal Women: Study
March 22, 2018 - Higher Dose Tx Deemed Safe in Pulmonary TB
March 22, 2018 - Discovery of new ALS gene points to cytoskeleton as potential target for drug development
March 22, 2018 - Diet soda associated with higher odds of diabetic retinopathy
March 22, 2018 - LSD reduces ‘sense of self’
March 22, 2018 - Vitamin D deficiency linked to metabolic syndrome in postmenopausal women
March 22, 2018 - Changes in the intestines may be responsible for reversal of diabetes after bariatric surgery
March 22, 2018 - iPads and Cancer; Clot Retrieval and Stroke: It’s PodMed Double T!
March 22, 2018 - Premature births linked to changes in mother’s bacteria
March 22, 2018 - Brain SPECT scans predict treatment outcomes in patients with depression
March 21, 2018 - Researchers succeed in integrating artificial organelles into cells of living organism
March 21, 2018 - Researchers discover ‘missing mutation’ in severe infant epilepsy
March 21, 2018 - Researchers develop statistics-based computational scheme to zoom in on brain function
March 21, 2018 - Verge joins Genomics England’s Discovery Forum industry partnership
March 21, 2018 - Trovagene Announces First Patient Successfully Completes Cycle 1 of Treatment with PCM-075 in Combination with Low Dose Cytarabine (LDAC) in AML Trial
March 21, 2018 - Congenital Cardiac Cath Tx Often Strays from Guidelines
March 21, 2018 - Marked increase in cardiovascular risk factors in women after preeclampsia
March 21, 2018 - New app may help predict, track manic and depressive episodes in bipolar patients
March 21, 2018 - Discovery of genes could lead to development of novel therapies for EBV-related cancers
March 21, 2018 - High-fat, high-cholesterol diet depletes ranks of artery-protecting immune cells
March 21, 2018 - Research misconduct allegations shadow likely CDC appointee
March 21, 2018 - Most Breast Ca Patients Fail to Get Genetic Counseling
March 21, 2018 - Lopsided ear function can lead to lopsided brain development
March 21, 2018 - Acupuncture helps manage menopausal symptoms, review finds
March 21, 2018 - Motor skill training may contribute to reading skills in obese children
March 21, 2018 - Poor dental health may be related to increased diabetes risk
March 21, 2018 - Chronic opioid users at increased risk of complications after spinal fusion surgery
March 21, 2018 - Study uncovers potential therapeutic target against large family of parasites
March 21, 2018 - NSAID use linked to increased risk of atrial fibrillation
March 21, 2018 - Scientists develop brain “stethoscope” that can detect silent seizures
March 21, 2018 - New method predicts effects of global warming on disease
March 21, 2018 - Insurance Company Hurdles Burden Doctors, May Harm Patients
March 21, 2018 - Renal Transplant from HCV-Positive Donors Feasible
March 21, 2018 - Myelodysplastic syndrome: MedlinePlus Medical Encyclopedia
March 21, 2018 - Research reveals brain mechanism involved in language learning
March 21, 2018 - Many parents still hesitate to try early peanut introduction, survey finds
March 21, 2018 - Audiologist urges tinnitus sufferers facing ‘revolving door healthcare’ to seek support
March 21, 2018 - Study reveals impact of prostate cancer on wives and partners of sufferers
March 21, 2018 - ‘Almost a Miracle Drug’: What We Heard This Week
March 21, 2018 - Study shows NIH spent >$100 billion on basic science for new medicines
March 21, 2018 - Columbia researchers identify nerve cells that drive fruit fly’s escape behavior
March 21, 2018 - Sartorius Stedim Biotech selected by ABL Europe to supply single-use process technologies
March 21, 2018 - Increase in coffee consumption may help battle against colon cancer
March 21, 2018 - Hydrogel may accelerate healing of diabetic ulcers
March 21, 2018 - Dermira’s Two Phase 3 Trials Evaluating Olumacostat Glasaretil in Patients with Acne Vulgaris Did Not Meet Co-Primary Endpoints
March 21, 2018 - DePuy Synthes introduces ACTIS Total Hip System for improving initial implant stability
March 21, 2018 - ‘Oh, It Was Nothing’
March 21, 2018 - Herbal drug kratom linked to salmonella illnesses, CDC says
March 21, 2018 - New optical point-of-care device could enhance screening for thyroid nodules
March 21, 2018 - FDA Expands Approval of Adcetris (brentuximab vedotin) for First-Line Treatment of Stage III or IV Classical Hodgkin Lymphoma in Combination with Chemotherapy
March 21, 2018 - Eosinophilic Esophagitis: Late Manifestation of Allergic March
March 21, 2018 - Signaling pathway involving the Golgi apparatus identified in cells with Huntington’s disease
March 21, 2018 - Quintupling inhaled steroid doses may not benefit children with asthma
March 21, 2018 - Study shows clear connection between cardiovascular fitness in middle age and dementia risk
March 21, 2018 - Premature babies have higher risks of health complications in Bangladesh
March 21, 2018 - Child’s temperament and parenting influence weight gain in babies
March 21, 2018 - Researchers find the heart to be capable of arrhythmia termination after local gene therapy
March 21, 2018 - Inhealthcare to provide digital infrastructure for NHS to help protect people from falls
March 21, 2018 - Flu Season Finally Slowing Down
March 21, 2018 - Mixed Results for Shorter DAPT in ACS Patients
March 21, 2018 - Scientists discover fish scale-derived collagen effective for healing wounds
March 21, 2018 - Genomics England announces new partnership to improve efficiency of next-generation sequencing analysis
March 21, 2018 - Adjuvant AC chemotherapy found to be effective in treating HRD-positive breast cancer patients
March 21, 2018 - Researchers identify new treatment targets for lung diseases using big data
March 21, 2018 - Kids see more women in science than five decades ago
March 21, 2018 - Research shows link between chronic fatigue syndrome and lower thyroid hormone levels
March 21, 2018 - Alzheimer’s disease on the rise
March 21, 2018 - Two Agents Equal as Pretreatment for Adrenal Tumor Surgery
March 21, 2018 - ‘Icebreaker’ protein opens genome for T cell development, researchers find
March 21, 2018 - Women in medicine shout #Metoo about sexual harassment at work
March 21, 2018 - Mother’s pre-pregnancy waist size may be linked to child’s autism risk
Chinese scientists establish synthesis of promising compound to fight against pancreatic cancer

Chinese scientists establish synthesis of promising compound to fight against pancreatic cancer

image_pdfDownload PDFimage_print

Intriguing antitumor activity is found in a very promising class of natural compounds: cyclic depsipeptides, which have a challenging structure that makes their investigation difficult. Now, Chinese scientists have established the synthesis of a member compound, which is especially promising in killing pancreatic cancer stem cells. They describe its total synthesis and first test results in the journal Angewandte Chemie; the results point to an unprecedented activity towards one of the deadliest cancers.

The almost uniform and threatening lethality of pancreatic cancer originates in its stem cells. These pancreatic cancer stem cells (PCSCs) are resistant against even the most aggressive treatments, which makes the search for new and powerful drugs indispensable. A very promising compound class are naturally occurring cyclic depsipeptides, peptide rings that contain one or more ester bonds in addition to peptidic amide bonds. Cyclic depsipeptides are found in a variety of organisms such as fungi, bacteria, and marine organisms and were shown to exert a diverse spectrum of biological activities including and anticancer performances. But how to do testing without material? The natural products are so rare they cannot be isolated in enough quantity, and their synthesis is hampered by a very complicated chemical structure. Furthermore, it is even not completely clear which parts of the molecule are the actual therapeutically active sites, least their mechanism of action.

A team of scientists around Liang Wang and Yue Chen from Tianjin Key Laboratory of Molecular Drug Research at Nankai University, China, has apparently made an end to that. Applying themselves to the task of total synthesis of a depsipeptide with the very technical name BE-43547A(2), which has a structure featuring different kinds of joints of the subparts, three chiral centers, and two double bonds, the scientists finally achieved its synthesis over 15 linear steps. They even produced the relatively large quantity of more than one-third of a gram of pure material–enough to perform first laboratory tests on its anticancer performance in comparison with other drugs and to investigate its structure-activity relationship.

The scientists found that the compound’s anticancer activity was far better than that of several established drugs including two components that are already in clinical trial against PCSCs. BE-43547A(2) reduced the percentage of pancreatic cancer stem cells 21-fold relative to the control and abolished the tumor-initiating capability of the cells. “All of the biological assays indicate that BE-43547A(2) can selectively ablate pancreatic cancer stem cells,” the scientists reported. Furthermore, they established which sites in the molecule are the pharmacologically relevant ones since molecules synthesized with slight differences in these sites were not active. These important results directly point to the next task, which is to determine the still unknown mechanism of action. The successful synthesis of BE-43547A(2) may be a decisive step in the ongoing fight against pancreatic cancer.



Posted in: Drug Discovery & Pharmaceuticals | Medical Science News | Medical Research News | Medical Condition News

Tags: Bacteria, Cancer, Clinical Trial, Compound, Drugs, Laboratory, Medicinal Chemistry, Molecule, Pancreatic Cancer, Pharmacy, Tumor

Tagged with:

About author

Related Articles