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

Emmanuel Israel Edache,Gideon Adamu Shallangwa,Adamu Uzairu,Paul Andrew Mamza

doi:10.1186/s43094-021-00367-4

Emmanuel Israel Edache, Gideon Adamu Shallangwa + Show 2 more

Open Access

https://doi.org/10.1186/s43094-021-00367-4

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Abstract

BackgroundThe 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.ResultsThe 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.ConclusionOutcomes of the study can further be exploited to develop potent inclusion (IncA) membranes inhibitors.

Highlights

The most frequent bacterial sexually transmitted disease is Chlamydia trachomatis (STD)
We report the molecular modeling of salicylidene acylhydrazides derivatives to continue our ongoing research on Chlamydia trachomatis inhibitor molecular modeling
With Molegro Virtual Docker (MVD) and PyRx software, all the standard drugs and ligands were docked with the protein structure and the best-docked molecules were listed depending on their MolDock score, Rerank score, hydrogen bond, and binding affinity as given in Tables 4 and 5

Summary

Introduction

The most frequent bacterial sexually transmitted disease is Chlamydia trachomatis (STD). Chlamydia trachomatis is a parasite that lives only inside cells. According to the World Health Organization, 92 million new instances of Chlamydia trachomatis infection occur each year [4]. Infections caused by multidrug-resistant Chlamydia trachomatis are on the rise in hospitals, especially in the intensive care unit (ICU), and are linked to greater expenses, increased morbidity, and high fatality rates [15]. As a result, finding new strong, safer, and less expensive Chlamydia trachomatis or bacterial inhibitors has become the greatest problem the human race has ever faced. For this reason, the development of new drugs able to fight Chlamydia trachomatis is still in great interest

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