Small GTPase protein Rho-kinase (ROCK) plays an important role in the pathogenesis of hypertension. Inhibition of ROCK II brings about the biochemical changes leading to vascular smooth muscles relaxation, finally resulting into potent antihypertensive activity. In the quest for potent ROCK-II inhibitors, a ligand-based pharmacophore containing four essential chemical features, namely two hydrogen bond acceptor (HBA), one hydrogen bond donor (HBD), and one hydrophobe (HY), was developed and rigorously validated. The pharmacophore was used for virtual screening, and hits retrieved from the National Cancer Institute (NCI) database were sorted on the basis of fit value, estimate value, and Lipinski's violation. Potential feature interaction of hits was also observed during docking studies with the amino acids present in the active site of Rho-kinase. Based on the above screening, three hits (NSC 2488, NSC 2888, and NSC 4231) were chosen and subjected to in vitro Rho-kinase enzyme-based assay, followed by ex vivo rat aortic vasodilatory assay. All three compounds showed good biological activity as predicted by the model and confirmed by the docking studies.

Background: Metabolic syndrome, also referred to as Syndrome X or obesity syndrome is a cluster of diseases prevalent worldwide in both developed and developing countries. According to WHO, it is referred to as a pathological condition wherein multiple disorders are manifested in the same individual. These include hypertension, hyperglycemia, dyslipidemia and abdominal obesity. Scope of the problem: Metabolic syndrome is one of the most serious non-communicable health hazards that have gained pivotal importance in the present scenario. The increasing prevalence affecting around 25 % of the world populace, mainly attributes to the acceptance of western culture, i.e. the intake of high-calorie food along with a substantial decrease in manual labor and adoption of sedentary lifestyles. Therefore, its timely prevention and management are the dire need in the present scenario. Methods: For successful accomplishment of the present review, an exhaustive analysis was performed utilizing a pool of previous related literature. The terms used during the search included ‘metabolic syndrome, prevalence, etiology, current pharmacotherapy for metabolic syndrome, etc. PUBMED, Medline and SCOPUS were explored for the study of abstracts, research and review papers in the quest for related data. The articles were downloaded and utilized for a meta-analysis study approach. Conclusion: In this review, an attempt was made to apprehend and summarize the epidemiology and treatment strategies for metabolic syndrome with a better understanding of its pathogenesis. It was postulated that an early diagnostic approach and subsequent line of treatment is required to prevent the deterioration of an individual’s health and life.

Background: Chitinases are the evolutionary conserved glycosidic enzymes that are characterized by their ability to cleave the naturally abundant polysaccharide chitin. The potential role of chitinases has been identified in the manifestation of various allergies and inflammatory diseases. In recent years, chitinases inhibitors are emerging as an alluring area of interest for the researchers and scientists and there is a dire need for the development of potential and safe chitinase antagonists for the prophylaxis and treatment of several diseases. Objective: The present review expedites the role of chitinases and their inhibitors in inflammation and related disorders. Methods: At first, an exhaustive survey of literature and various patents available related to chitinases were carried out. Useful information on chitinases and their inhibitor was gathered from the authentic scientific databases namely SCOPUS, EMBASE, PUBMED, GOOGLE SCHOLAR, MEDLINE, EMBASE, EBSCO, WEB OF SCIENCE, etc. This information was further analyzed and compiled up to prepare the framework of the review article. The search strategy was conducted by using queries with key terms “ chitin”, “chitinase”, “chitotrisidase”, “acidic mammalian chitinase”, “chitinase inhibitors”, “asthma” and “chitinases associated inflammatory disorders”, etc. The patents were searched using the key terms “chitinases and uses thereof”, “chitinase inhibitors”, “chitin-chitinase associated pathological disorders” etc. from www.google.com/patents, www.freepatentsonline.com, and www.scopus.com. Results: The present review provides a vision for apprehending human chitinases and their participation in several diseases. The patents available also signify the extended role and effectiveness of chitinase inhibitors in the prevention and treatment of various diseases viz. asthma, acute and chronic inflammatory diseases, autoimmune diseases, dental diseases, neurologic diseases, metabolic diseases, liver diseases, polycystic ovary syndrome, endometriosis, and cancer. In this regard, extensive pre-clinical and clinical investigations are required to develop some novel, potent and selective drug molecules for the treatment of various inflammatory diseases, allergies and cancers in the foreseeable future. Conclusion: In conclusion, chitinases can be used as potential biomarkers in prognosis and diagnosis of several inflammatory diseases and allergies and the design of novel chitinase inhibitors may act as key and rational scaffolds in designing some novel therapeutic agents in the treatment of variety of inflammatory diseases.

In line with the overhead discussion, and through our stepwise computational approaches, we have identified novel, structurally diverse glycogen synthase kinase inhibitors.

Background: Alzheimer’s disease is neurological condition causing cognitive inability and dementia. The pathological lesions and neuronal damage in brain is caused by self-aggregated fragments of mutated Amyloidal precursor protein (APP). Objective: : The controlled APP processing by inhibition of secretase is the strategy to reduce Aβ load to treat Alzheimer’s disease. Method: A QSAR study was performed on 55 Pyrrolidine based ligands as BACE-1 inhibitors with activity magnitude of greater than 4.of compounds. Results: In an advent to design new BACE-1 inhibitors, the pharmacophore model with correlation (r = 0.90) and root mean square deviation (RMSD) of 0.87 was developed and validated. Further, the hits retrieved by in-silico approach were evaluated by docking interactions. Conclusion: Two structurally diverse compounds exhibited Asp32 and Thr232 binding with the BACE-1 receptor. The aryl substituted carbamate compound exhibited highest fit value and docking score. The biological activity evaluation by in-vitro assay was found to be >0.1µM.