Computer-aided modeling of triazole analogues, docking studies of the compounds on DNA gyrase enzyme and design of new hypothetical compounds with efficient activities

Abstract

The increasing problem of multi-drug resistant-tuberculosis has focused attention on developing new drugs that are not only active against drug-resistant tuberculosis, but also shorten the lengthy therapy. Therefore, this work employs the application of modeling technique to predict the inhibition activities of some prominent compounds which been reported to be efficient against Mycobacterium tuberculosis. To accomplish the purpose of this work, multiple regression and genetic function approximation were adopted to create the model. The established model was swayed with topological descriptors; MATS7s, SpMin4_Bhv, TDB3v and RDF70v. More also, interactions between the compounds and the target protein 'DNA gyrase' were evaluated via molecular docking approach utilizing the PyRx and discovery studio simulation software. Based on the docking analysis, compound 20 has the most noticeable binding affinity of -16.5 kcal/mol. Therefore, compound 20 served as a reference structural template and insight to design fourteen novel hypothetical agents with more prominent anti-tubercular activities. More also, compound 20j was observed with the highest activity among the designed compounds with a prominent binding affinity of -24.3 kcal/mol. Therefore, this research recommends in-vivo, in-vitro screening and pharmacokinetic properties to be carried out in order to determine the toxicity of the designed compounds.Communicated by Ramaswamy H. Sarma.

Keywords: DNA gyrase; Descriptors; QSAR; triazole; tuberculosis.