Insight into structural features and supramolecular architecture of synthesized quinoxaline derivatives with anti-leishmanial activity, in vitro

Abstract

An estimated 50,000 deaths annually are reported due to neglected tropical diseases (NTDs), among which Leishmaniasis is considered to be a major tropical disease by the WHO. The present work comprises synthesis of six quinoxaline derivatives (1–6) with Br, Cl, F, OCH3, and CF3 substitutions, including three new analogues (2, 4, and 6) followed by detailed structural studies on the basis of 1H-, and 13C NMR, and single-crystal X-ray Diffraction studies followed by evaluation of their antileishmanial potential (in vitro) against promastigotes forms of Leishmania major, and Leishmania tropica in comparison to three well known standard drugs Amphotericin B, pentamidine and miltefosine (the only approved drug for oral use to treat leishmaniasis). Detailed qualitative and quantitative analysis of supramolecular features reveals the significant contributions of H⋅⋅⋅Br, H⋅⋅⋅Cl, H⋅⋅⋅C, and H⋅⋅⋅F contacts towards structural stability. The observed results depicted that among tested compounds chloro substituted quinoxaline analogues 1 (IC50 = 23.30 ± 0.12 μM), 3 (IC50 = 23.30 ± 0.12 μM), and methoxy substituted 5 (IC50 = 23.30 ± 0.12 μM) possess the promising activity against Leishmania major in comparison the tested standard drug miltefosine (IC50 = 25.78 ± 0.2 μM). All synthesized compounds were appeared to be non-cytotoxic against the tested BJ human fibroblast cell line at a concentration of 30 μM.