Synthesis, Antileishmanial Activity and Qsar Study of (1,3,4-Thiadiazol-2-Ylthio) Acetamides Derived From 5-Nitrofuran Publisher



Vosooghi M¹ ; Sabourian R¹ ; Tahghighi A¹ ; Mahdavi M¹ ; Emami S² ; Razmi S³ ; Kabudanian Ardestani S³ ; Safavi M³ ; Foroumadi P⁴ ; Kaveh S¹ ; Khoshneviszadeh M^{1, 5} ; Edraki N^{1, 5} ; Shafiee A¹ ; Foroumadi A^{1, 4}
Source: Medicinal Chemistry Research Published:2015

Abstract

A novel series of (1,3,4-thiadiazol-2-ylthio)acetamides derived from 5-nitrofuran were synthesized and evaluated against extracellular promastigotes of Leishmania major. The most potent anti-promastigote compounds were also evaluated in vitro against intracellular amastigotes. All compounds showed better activity than standard drug Glucantime. The most potent compounds against the promastigotes were found to be N-(3,4-dimethoxyphenethyl)-2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylthio) acetamide (5q) and 2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylthio)-N-propylacetamide (5r) with IC50 values less than 20 μM. Although, the cytotoxic evaluation of target compounds against mouse peritoneal macrophages demonstrated that these series of compounds have cytotoxicity at concentrations higher than 50 μM, but most of them exhibited antileishmanial activity at non-cytotoxic concentrations. QSAR study indicated that 2D-autocorrelation and topological descriptors are influential parameters in the antileishmanial activity. © 2014 Springer Science+Business Media New York.