Virtual screening, pharmacokinetics, and molecular dynamics simulations studies to identify potent approved drugs for Chlamydia trachomatis treatment

Abstract

Background: The most frequent bacterial sexually transmitted disease is Chlamydia trachomatis (STD). In 2010, the Centers for Disease Control and Prevention (CDC) received 1.3 million reports of cases (CDC). Human chlamydial infections are linked to a variety of clinical symptoms. Inclusion (IncA) membranes are a promising drug target for the treatment of Chlamydia trachomatis. In the present study, molecular docking, ADMET, golden triangle, and molecular dynamics (MD) simulation studies were performed on a series of salicylidene acylhydrazides derivatives against Chlamydia trachomatis. Three types of docking software with different algorithms were used to screen the potential candidate against Chlamydia trachomatis. Results: The results obtained from the docking analysis succeeded in screening nine novel hit compounds with high affinity to IncA membranes. Then, pharmacokinetics properties were calculated to spot out the drug-likeness of the selected compounds. Also, golden triangles were performed on the selected compounds. Compounds outside the golden triangle indicate that they would have clearance problems. Out of the nine novel hits drugs, four compounds pass the golden triangle screening and virtually all the quality assurance tests proposed by the model and were used for further analysis. One-ns molecular dynamics simulations on the docked complex of compound 44 (one of the highly active selected compounds of the dataset) aided in the further exploration of the binding interactions. Some crucial residues such as Ser111, Gln114, Asn107, Leu142, Gly144, Gln143, Lys104, Tyr149, Phe108, Phe145, and Arg146 were identified. Conventional and carbon-hydrogen bond interactions with amino residues Arg146, Asn107, Phe145, and Ser111 were critical for the binding of inclusion (IncA) membranes inhibitors. Conclusion: Outcomes of the study can further be exploited to develop potent inclusion (IncA) membranes inhibitors.