Monoamine oxidase B (MAO-B) is an important drug target for the treatment of neurological disorders. A series of 6-nitrobenzothiazole-derived semicarbazones were designed, synthesized, and evaluated as inhibitors of the rat brain MAO-B isoenzyme. Most of the compounds were found to be potent inhibitors of MAO-B, with IC(50) values in the nanomolar to micromolar range. Molecular docking studies were performed with AutoDock 4.2 to deduce the affinity and binding mode of these inhibitors toward the MAO-B active site. The free energies of binding (ΔG) and inhibition constants (K(i)) of the docked compounds were calculated by the Lamarckian genetic algorithm (LGA) of AutoDock 4.2. Good correlations between the calculated and experimental results were obtained. 1-[(4-Chlorophenyl)(phenyl)methylene]-4-(6-nitrobenzothiazol-2-yl)semicarbazide emerged as the lead MAO-B inhibitor, with top ranking in both the experimental MAO-B assay (IC(50): 0.004±0.001 μM) and in computational docking studies (K(i): 1.08 μM). Binding mode analysis of potent inhibitors suggests that these compounds are well accommodated by the MAO-B active site through stable hydrophobic and hydrogen bonding interactions. Interestingly, the 6-nitrobenzothiazole moiety is stabilized in the substrate cavity with the aryl or diaryl residues extending up into the entrance cavity of the active site. According to our results, docking experiments could be an interesting approach for predicting the activity and binding interactions of this class of semicarbazones against MAO-B. Thus, a binding site model consisting of three essential pharmacophoric features is proposed, and this can be used for the design of future MAO-B inhibitors.
Context Xanthone derivatives have been reported to possess a wide range of biological properties. In effort to search new effective antihypertensive compounds, we have synthesizednovel xanthone derivatives (xanthonoxypropanolamines) and got patent for these compounds (The Patent Office, Government of India, S. No.: 011–016308, Patent No.: 250538). Objective In the present work, we attempted to establish the antihypertensive activity, toxicity and molecular docking study forthese newly synthesized compounds (1a, 1b and 2). Materials and method The preliminary antihypertensive screening was performed by administering synthesized compounds and standard drugs intraperitonially and orally into wistar rats. The change in systolic, diastolic and the mean blood pressure before and after the treatment of the drugs was measured on a Digital LE-S100 Blood Pressure Meter by Tail-cuff method non-invasively. Toxicity studies were carried out after oral administration of synthesized compounds to rats at doses of 25, 50, and 100mg/kg. The serum samples were tested for different toxicity parameters such as liver function test, kidney function test etc. The docking simulations of all the compounds were performed using Maestro, version 9.4 implemented from Schrodinger software suite. Results and discussion The result showed that the compound 1a, 1b and 2 have greater antihypertensive activity with almost equal or less toxicity profile in comparison to standard drug Propranolol and Atenolol. The docking score for the compound 1b was found -9.1 while for compound 1a and 2 were found -8.7 and -8.6 respectively. Conclusion These novel compounds i.e. 1a, 1b, and 2 have greater antihypertensive activity in comparison to standard drugs Propranolol and Atenolol. All these compounds do not have any toxicity.
Covid-19, a disease caused by severe acute respiratory syndrome corona virus (SARS-CoV) has challenged pharmaceutical science against viruses, globally. The disease has become a global pandemic beginning the race of new therapeutic strategies against novel corona virus (nCoV). Therefore, management of such pandemic issue is a need of the hour. Drug delivery refers to an approach adopted to transfer drug particles within the body to obtain a potent therapeutic effect. In the present study, an attempt has been taken to discuss about plant secondary metabolites (PSMs) and fungal bioactive compounds which are potent antiviral pharmaceutical agents. Also, a discussion about allopathic ingredient of plant secondary metabolites have also been done. The unique repository of Indian plants and versatility of fungal species provide broad spectrum to screen for pharmaceutical ingredients against novel corona virus. Further, screening of plant secondary metabolites by molecular docking can be a cost effective way to combat from novel corona virus. Thus, it can be said that, Multidimensional approach discussed herein may provide insights to combat antimicrobial resistance in the future. The present review will promote further research horizons in plants and fungal based therapeutics and a novel approach towards drug discovery thereby preventing the humans from suffering through severe adversities.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.