Pharmacoinformatics

Abstract: At present, the world is facing a pandemic named as COVID-19, caused by SARS-CoV-2 Traditional Chinese medicine has recommended the use of liquorice (Glycyrrhiza species) in the treatment of infec

Abstract: Pharmaceutics, Bio Pharmaceutics and Pharmacokinetics, Novel Drug Delivery System, Pharmaceutical chemistry including medicinal and analytical chemistry; Pharmacognosy including herbal products standardization and Phytochemistry; Pharmacology, Bio Technology: Allied sciences including drug regulatory affairs, Pharmaceutical Marketing, Pharmaceutical Microbiology, Pharmaceutical biochemistry, Pharmaceutical Education and Hospital Pharmacy.Â

Abstract: Spice-rich recipes are referred to as "functional foods" because they include a variety of bioactive chemicals that have health-promoting properties, in addition to their nutritional value. Using pharmacoinformatics-based analysis, we explored the relevance of bioactive chemicals found in Rasam (a South Indian cuisine) against oxidative stress-induced human malignancies. The Rasam is composed of twelve main ingredients, each of which contains a variety of bioactive chemicals. Sixty-six bioactive compounds were found from these ingredients, and their structures were downloaded from Pubchem. To find the right target via graph theoretical analysis (mitogen-activated protein kinase 6 (MAPK6)) and decipher their signaling route, a network was built. Sixty-six bioactive compounds were used for in silico molecular docking study against MAPK6 and compared with known MAPK6 inhibitor drug (PD-173955). The top four compounds were chosen for further study based on their docking scores and binding energies. In silico analysis predicted ADMET and physicochemical properties of the selected compounds and were used to assess their drug-likeness. Molecular dynamics (MD) simulation modelling methodology was also used to analyse the effectiveness and safety profile of selected bioactive chemicals based on the docking score, as well as to assess the stability of the MAPK6-ligand complex. Surprisingly, the discovered docking scores against MAPK6 revealed that the selected bioactive chemicals exhibit varying binding ability ranges between - 3.5 and - 10.6 kcal mol-1. MD simulation validated the stability of four chemicals at the MAPK6 binding pockets, including Assafoetidinol A (ASA), Naringin (NAR), Rutin (RUT), and Tomatine (TOM). According to the results obtained, fifty of the sixty-six compounds showed higher binding energy (- 6.1 to - 10.6 kcal mol-1), and four of these compounds may be used as lead compounds to protect cells against oxidative stress-induced human malignancies.

Abstract: This study is the first one to construct the reliable structure of the α1/γ2 interface of Gamma aminobutyric acid type A (GABA-A) receptor by homology modeling and refined every loop of the whole protein structure. The modeling GABA-A receptor was validated by docking the control compounds in binding site, checking the key residue in α1/γ2 interface, probability density function (PDF) value, and Ramachandran plot. This paper is also the first one to propose that jujubogenin is the effective component in suanzaoren decoction, neither jujuboside A nor jujuboside B by chemoinformatics and pharmacoinformatics approach. In addition, pharmacophore analysis showed that the oxygens on jujubogenin approached α1-TYR160 and γ2-LYS184, respectively. The comparative molecular field analysis (CoMFA) model yielded a q cv 2 value of 0.731 and an r2 of 0.942 at 5 components. Comparative molecular similarity indices analysis (CoMSIA) produced a q cv 2 of 0.617 and an r2 of 0.921 at 5 components. The CoMFA and CoMSIA models showed statistically significant results. Hence, based on the results of docking, ADMET descriptor, pharmacophore, and three-dimensional quantitative structure–activity relationship (3D-QSAR) studies, the jujubogenin was suggested to be the effective GABA-A agonist in suanzaoren decoction.