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.

Developing imidazole analogues as potential inhibitor forLeishmania donovanitrypanothione reductase: virtual screening, molecular docking, dynamics and ADMET approach

“…This drug has shown minimal side effect with antileishmanial activity in animal model, when it was administered orally (Wyllie, Patterson, & Fairlamb, 2013;Wyllie et al, 2012). interactions (Hazra et al, 2013;Verma et al, 2012) (Sahoo et al, 2014).…”

“…The key purpose of our study is to predict interaction of the main binding sites of a ligand with a targeted enzyme of three-dimensional structure results in docking score (Venkatesan, Shukla, & Dubey, 2010;Verma et al, 2012). ADMET and QikProp studies were carried out to check toxicity associated with ligand and it was found that maximum number of 5-Nitroimidazole analogues have shown MRTD values above 3.4…”

“…Grid generation is a way to decide a site on the target protein where ligand interact during Among all these amino acid residues Lys-61 from B chain and Ser-464, Met-400 and Leu-399 from A chain participated in H-bond formation (Verma et al, 2012). The size of grid depends on the size of selected large ligand which require small size of grid for more specific result.…”

“…Molecular docking approach assist the protein interactions with ligand, other proteins, or surfaces and these are controlled by a complex array of intermolecular interactions (Hazra et al, 2013;Verma et al, 2012). The final goal of molecular docking is to predict the biological activity of given ligand.…”

High-throughput virtual screening and quantum mechanics approach to develop imipramine analogues as leads against trypanothione reductase of leishmania

“…However, the residues occupying the active site were Cys-52 and Cys-57 form chain-B. These residues are conserved and surrounded by aforementioned H-bond forming amino acid residues [18]. Ligand showing interaction with these two amino acid residues might change the active site structure leads to enzyme inhibition and ultimately parasite clearance.…”