From hit discovery through lead optimization and beyond, computational methods have become an essential part of many drugs development processes. There are typically several steps in the docking process, and each one provides a new level of complexity. Docking methods are used to place small molecules in the active region of the enzyme. In addition to these methods, scoring functions are used to estimate a compound's biological activity by looking at how it interacts with prospective targets. Molecular docking is considered to be the most widely utilized computational phenomenon in the field of computer-aided drug design (CADD). It is being utilized at the academic level as well as in pharmaceutical companies for the lead discovery process. Molecular docking is mainly associated with two terms: ligand and protein. Protein is the target site where ligand may bind to give specific activity. Molecular docking provides information on the ability of the ligand to bind with protein which is known as binding affinity. Applications of molecular docking in drug development have evolved significantly since it was first created to aid in the study of molecular recognition processes between small and large compounds. This review emphasizes the basic features of molecular docking along with the types, approaches and applications.

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Introduction: Stroke is a potentially fatal condition that is defined by the fast development of clinical symptoms of ischemia. Numerous flavonoids have been demonstrated in animal models to ameliorate brain ischemia-reperfusion damage. Piperine is a flavonoid derived from Piper nigrum L. that exhibits a variety of pharmacological effects. The purpose of this research was to determine if Piper nigrum L. has a protective effect against the brain damage caused by bilateral common carotid artery occlusion (BCCAO) in rats. Materials and Methods: The animal study was certified by Institutional Animal Ethics Committee (IAEC) under research project no. RKCP/COI/RP/12/28. Numerous parameters were evaluated to ascertain the extent of oxidative stress and eventual protection of Piper nigrumL. including glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), lipid peroxidation (LPO), brain protein, and calcium levels in brain homogenate. The preventive effect of P. nigrum was evaluated and compared with quercetin as a standard using histopathology and the region of cerebral infarction. Results: In our research, we observed a substantial rise in superoxide dismutase (SOD), catalase, glutathione, and brain protein levels and a fall in lipid peroxidation and calcium levels in the P. nigrum and quercetin treated groups with the level of significance (p value) less than 0.05, confirming the protective effect against brain injury. Additionally, P. nigrum was shown to provide less protection compared to quercetin. Conclusion: As a result of these data, we hypothesise that P. nigrummay have a considerable neuroprotective effect in the brain against ischemic/ reperfusion-induced oxidative damage.

Background: p-propoxybenzoic acid (p-PBA) is reported as an active chemical constituent of medicinal plants that possess anti-diabetic activity. It is termed a Multiple-Designed Ligand (MDL) having the ability to block more than one enzyme. A molecular docking study justifies the binding ability of p-PBA with acarbose and NaVO4 which were considered standard compounds having the ability to block target enzymes. α-amylase inhibition assay was used as an in-vitro screening model to evaluate the activity of p-PBA against diabetes on an initial basis. Methods: For the molecular docking study, a PDB file of p-PBA was prepared and PDB files of α-amylase (1C8Q), α-glucosidase (5KZW) and PTP1B (5K9W) were procured. p-PBA was docked against the enzymes using the blind docking method. The binding score of p-PBA and standard with enzymes was obtained and compared. The percentage inhibition of an α-amylase enzyme by p-PBA was measured by using a DNS-modified α-amylase inhibition assay and half-maximal inhibitory concentration (IC50) was calculated. Results: p-PBA has a significant inhibitory effect against α-amylase, α-glucosidase, and PTP1B with docking scores of 8.43 ± 0.44 kcal/mol, 9.19 ± 0.49 kcal/mol, and 9.40 ± 0.47 kcal/mol respectively. IC50calculated from the results of α-amylase inhibition assay p-PBA was 56.59 μg/mL. Conclusion: A combination of in-silico and in-vitro methods assessed p-PBA’s anti-diabetic potential on an initial basis. A molecular docking study involving p-PBA concluded the affinity of p-PBA to α-amylase, α-glucosidase, and PTP1B was significantly correlated with the affinity of acarbose and NaVO4. In-vitro α-amylase assay validated the compound’s inhibitory action against the enzyme.

This study provides a comprehensive overview of safety pharmacology practises, technologies, and emerging concepts in drug discovery and development. The field of safety pharmacology serves a crucial role in anticipating and minimising the hazards and adverse effects of new medications. Evaluation of important organ systems, such as the cardiovascular, central nervous, respiratory, gastrointestinal, and renal systems, is involved. While the main battery of safety pharmacology research focuses on major organ systems, additional studies may be done depending on the unique properties of prospective medications. The research emphasises the significance of evaluating the gastrointestinal and renal systems and addresses the many approaches, biomarkers, and technologies used to enhance safety evaluations. In addition, new ideas like as frontloading, alternative models, and the incorporation of safety pharmacology endpoints into regulatory toxicology studies are investigated. These developments help to better informed decision-making and lead candidate selection, eventually improving the safety and effectiveness of novel treatments.