title: Molecular Docking and in Vitro Antileishmanial Evaluation of Chromene-2-thione Analogues.
abstract: Leishmaniases are an epidemic in various countries, and the parasite is developing resistance against available drugs. Thus, development of new drugs against Leishmania is an open area of investigation for synthetic organic chemists. To meet this challenge, a series of chromene-2-thione derivatives have been synthesized and docked into the active site of trypanothione reductase (TryR) enzyme required for redox balance of the parasite. These were screened on promastigote, axenic amastigote, and intracellular amastigote stages of Leishmania donovani and found to show high levels of antileishmanial activity together with minimal toxicity to human peripheral blood mononuclear cells. Compounds 3b and 3k were found to be the most active among the tested compounds. Although the compounds show moderate antileishmanial activity, they identify a chemical space to design and develop drugs based on these chromene-2-thione derivatives against the Leishmania parasite.
authors.affiliation: Department of Chemistry and Centre of Advanced Study, Faculty of Science, Banaras Hindu University , Varanasi-221005, India.
authors.forename: Rajiv Kumar
authors.initials: RK
authors.lastname: Verma
authors.affiliation: Infectious Disease Research Laboratory, Institute of Medical Sciences, Banaras Hindu University , Varanasi-221005, India.
authors.forename: Vijay Kumar
authors.initials: VK
authors.lastname: Prajapati
authors.affiliation: Department of Chemistry and Centre of Advanced Study, Faculty of Science, Banaras Hindu University , Varanasi-221005, India.
authors.forename: Girijesh Kumar
authors.initials: GK
authors.lastname: Verma
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Guwahati , Assam-781039, India.
authors.forename: Deblina
authors.initials: D
authors.lastname: Chakraborty
authors.affiliation: Infectious Disease Research Laboratory, Institute of Medical Sciences, Banaras Hindu University , Varanasi-221005, India.
authors.forename: Shyam
authors.initials: S
authors.lastname: Sundar
authors.affiliation: Infectious Disease Research Laboratory, Institute of Medical Sciences, Banaras Hindu University , Varanasi-221005, India.
authors.forename: Madhukar
authors.initials: M
authors.lastname: Rai
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Guwahati , Assam-781039, India.
authors.forename: Vikash Kumar
authors.initials: VK
authors.lastname: Dubey
authors.affiliation: Department of Chemistry and Centre of Advanced Study, Faculty of Science, Banaras Hindu University , Varanasi-221005, India.
authors.forename: Maya Shankar
authors.initials: MS
authors.lastname: Singh
keywords: Lipinsky rule; chromene-2-thione; molecular docking; trypanothione reductase; visceral leishmaniasis