Molecular modeling assisted identification and biological evaluation of potent cathepsin S inhibitors

Publication date: Available online 12 December 2019Source: Journal of Molecular Graphics and ModellingAuthor(s): Sabahuddin Ahmad, Sudha Bhagwati, Sushil Kumar, Dibyendu Banerjee, Mohammad Imran SiddiqiAbstractCathepsin S (CatS) is one of the cysteinyl cathepsins widely studied for its clinical significance and found to be a promising therapeutic target for several diseases; to name a few is arthritis, allergic inflammation, cancer, diabetes, obesity, and cystic fibrosis. Elevated CatS level is a contributing factor for related disorders, and therefore among different strategies to regulate the activity of CatS, one is to design a quality inhibitor. Earlier, we have demonstrated a highly selective CatS inhibitor, RO5444101 interacts primarily with the S2 pocket of the protein which is structurally unique in contrast to other variants of cathepsin. However, the molecular properties of RO5444101 can question its efficacy at the clinical level. In the present study, we have implemented a series of molecular modeling methods to screen the Maybridge library considering the pharmacophoric features of RO5444101 and other relevant inhibitors of CatS. Based on the priority list, eight hits were subjected to biological evaluation. Subsequently, KM07987 was found to be most potent, with the IC50 of
Source: Journal of Molecular Graphics and Modelling - Category: Molecular Biology Source Type: research

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Publication date: Available online 20 January 2020Source: Trends in Food Science &TechnologyAuthor(s): Qiong-Qiong Yang, Arakkaveettil Kabeer Farha, Gowoon Kim, Khalid Gul, Ren-You Gan, Harold CorkeAbstractBackgroundCurcumin has gained increasing attention in recent years due to its biological properties and photosensitivity. Curcumin-mediated photodynamic therapy has been used in antibacterial and anticancer applications. Considering the importance and rapid advances in curcumin-mediated photodynamic treatments and its related beneficial functions, a comprehensive and up-to-date review is timely to summarize the state...
Source: Trends in Food Science and Technology - Category: Food Science Source Type: research
Publication date: Available online 20 January 2020Source: Trends in Food Science &TechnologyAuthor(s): I.P. Shanura Fernando, BoMi Ryu, Ginnae Ahn, In-Kyu Yeo, You-Jin JeonAbstractBackgroundMetabolic syndrome (MS) defines a group of severe comorbidities, including insulin resistance, abnormal fat accumulation, and high blood pressure that lead to obesity, diabetes, and heart diseases. MS has received a growing concern due to its rising prevalence in many countries. The consumption of high-calorie food, sedentary lifestyle habits, genetic factors, and stress conditions aggravate risk factors for developing metabolic syn...
Source: Trends in Food Science and Technology - Category: Food Science Source Type: research
Publication date: Available online 20 January 2020Source: Trends in Food Science &TechnologyAuthor(s): Saikat Sen, Raja Chakraborty, Pratap KalitaAbstractBackgroundRice (Oryza sativa L.) is the most popular staple food grain and an important source of fibre, energy, minerals, vitamins, and other biomolecules. Rice parts exhibited a number of health beneficial effect in pre-clinical/clinical studies. Rice constituents are getting popularity in preparation of pharmaceutical adjuvant, food additives and supplements.Scope &approachIn this paper, we summarized the available literature on health-promoting and therapeutic...
Source: Trends in Food Science and Technology - Category: Food Science Source Type: research
Publication date: Available online 21 January 2020Source: Food ChemistryAuthor(s): A. Mohamed Anis, Yadahally N. SreeramaAbstractProtein glycation plays a vital role in the progression of various diabetes complications. Therefore, inhibition of protein glycation could be a key strategy to prevent these diabetic abnormalities. Evaluation of phenolic compositions and their antiglycation activity revealed that p-coumaric and chlorogenic acids were major phenolic acids in barnyard millet. These phenolics exhibited multiple antioxidant activities in various mechanisms and protected the oxidative DNA damage and hydroxyl radical-...
Source: Food Chemistry - Category: Food Science Source Type: research
CONCLUSIONS: The clinical polymorphism effectiveness outlined therein will be assured by diagnostic improvements suitable for driving treatment decisions. In light of our experimental results and literature data, the analysis of the SLCO1B1 T521C variant will allow clinicians to take advantage from a better treatment planned for their patients in order to minimize neuromuscular pain and maximize benefits. PMID: 31957862 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
Authors: Su Z, Liu HL, Qi B, Liu Y Abstract OBJECTIVE: To explore the influences of propofol on the proliferation and apoptosis of cardia cancer cells via mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway. PATIENTS AND METHODS: A total of 65 surgical resection specimens of cardia cancer were selected as research objects and divided into control group and with low (12.5 μmol/L), medium (25 μmol/L), and high (50 μmol/L) propofol concentration groups. The apoptosis of cancer cells, ERK1/2 phosphorylation level, expressions of Caspase-3, B-cell lymphoma-2 (...
Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
CONCLUSIONS: CD36 can mediate cell apoptosis by inhibiting the expression of the related proteins in nodal Wnt/β-catenin signaling pathway, and is expected to become a potential therapeutic target for clinical treatment of patients with diabetic nephropathy. PMID: 31957842 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
This study aimed at exploring the role of α-enolase (ENO1) in proliferation, invasion, and cell apoptosis in MDA-MB-231 and MCF-7 breast cancer human cells, to provide a theoretical basis for the clinical treatment of breast cancer. MATERIALS AND METHODS: MDA-MB-231 and MCF-7 cells were randomly divided into five groups: normal control group (Control group), negative control group (negative control virus, NC group), and shENO1 (sh1, sh2, and sh3) group, respectively. The expressions of ENO1 mRNA and protein were measured by Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively....
Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
CONCLUSIONS: NNT-AS1 participated in the progression of lung cancer through NNT-AS1/miR-3666/E2F2 regulatory axis at least in part. Our study supplied a promising strategy for the treatment of lung cancer. PMID: 31957837 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
Last week, I invited the venerable Lee Hood to speak to us at Harvard Medical School, and I was reminded again of his prescience in describing and advocating for "P4 Medicine" -- or predictive, preventive, personalized and participatory medicine -- over 10 years ago, in 2004! And while Lee's vision of P4 Medicine embraces a model of systems biology that is broader than just the genome, the democratization of genetic testing over the past decade falls squarely within the powerful narrative prediction and prevention. Indeed, much of the controversy surrounding direct-to-consumer (DTC) genetic testing when it launch...
Source: Science - The Huffington Post - Category: Science Source Type: news
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