Abstract

This study compares the nitro group position of thienyl imines bound to organometallic fragments, and the respective electrochemical and anti-parasitic properties. Ferrocenyl and cyrhetrenyl imines derived from 4-nitrothiophene (1a-3a) and 5-nitrothiophene (1b-3b) were synthesized and characterized by spectroscopic techniques. In addition, molecular structure of 1a, 2a and 3a were determined by X-ray crystallography. The reduction potential of the nitro group (E-1/2), determined by cyclic voltammetry, shows that imines with a 5-nitrothiophene moiety exhibit lower E-1/2 values (E-1/2 = -0.56 to -0.78 V) than 4-nitro derivatives (E-1/2 = -0.92 to -1.04 V), indicating that 5-nitro compounds better generate radical species. The 5-nitrothiophene derivatives (1b-3b) were more active against T. b. brucei (trypomastigotes) and T. cruzi (epimastigotes) than 4-nitrothiophene analogues (1a-3a). Enhanced trypanocidal properties in 5-nitrothiophenes may be due to NO2 group reduction being readily converted to their downstream, trypanocidal products. Based on the anti-parasitic activity and Selectivity Index determined for all derivatives, 1b emerged as an appropriated agent for treatment of trypanosomal infections. Additionally, evaluations of T. b. brucei susceptibility showed that compound 3b is a substrate for TbNTR1. Density Functional Theory (DFT) calculations were used as an approximation to rationalize the influence of nitro group positions on the heterocyclic ring regarding electrochemical behaviour and anti-parasitic activity. (C) 2020 Elsevier Ltd. All rights reserved.