QSAR Studies and Scaffold Optimization of Predicted Novel ACC 2 Inhibitors to Treat Metabolic Syndrome.

Background: Metabolic syndrome is one of the major non-communicable global health hazards of the modern world owing to its amplifying prevalence. Acetyl coenzyme-A carboxylase 2 (ACC 2) is one of the most crucial enzymes involved in the manifestation of this disease because of its regulatory role in fatty acid metabolism.

Objective: To find novel potent ACC 2 inhibitors as therapeutic potential leads for combating metabolic syndrome.

Metabolic Syndrome: The Constellation of Co-morbidities, A Global Threat.

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.

Identification of Novel Rho-Kinase-II Inhibitors with Vasodilatory Activity.

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.

Quantitative Structure-Activity Relationship Analysis of Selective Rho Kinase Inhibitors as Neuro-regenerator Agents.

Objectives: To understand the role of Rho (serine/threonine) kinases in the treatment of neurological segments, attempts have been made to find potent inhibitors of Rho enzyme by a 2D quantitative structure-activity relationship (QSAR) model.

Materials And Methods: QSAR studies were executed on urea-based scaffolds from aniline and benzylamine analogues, which were aligned for generation of a chemometric-based model. Multivariate statistical approaches were applied including linear and nonlinear analysis such as multiple linear regression, partial least square and artificial neural network for the generation of model, and also an application of () absorption, distribution, metabolism, excretion studies was performed to ascertain the novelty and drug-like properties of the intended molecules.

In-Silico QSAR Modelling of Predicted Rho Kinase Inhibitors Against Cardio Vascular Diseases.

Background: Rho-kinase is an essential downstream target of GTP-binding protein RhoA, and plays a crucial role in the calcium-sensitization pathway. Rho-kinase pathway is critically involved in phosphorylation state of myosin light chain, leading to increased contraction of smooth muscles. Inhibition of this pathway has turned out to be a promising target for several indications such as cardiovascular diseases, glaucoma and inflammatory diseases.

In-Silico Screening of Ligand Based Pharmacophore, Database Mining and Molecular Docking on 2, 5-Diaminopyrimidines Azapurines as Potential Inhibitors of Glycogen Synthase Kinase-3β.

Background: Glycogen synthase kinase-3β plays a significant role in the regulation of various pathological pathways relating to the Central Nervous System (CNS). Dysregulation of Glycogen synthase kinase 3 (GSK-3) activity gives rise to numerous neuroinflammation and neurodegenerative related disorders that affect the whole central nervous system.

Objective: By the sequential application of in-silico tools, efforts have been attempted to design the novel GSK-3β inhibitors.