Benzofuran-isatin-imine hybrids tethered via different length alkyl linkers: Design, synthesis and in vitro evaluation of anti-tubercular and anti-bacterial activities as well as cytotoxicity

Herein we report the design and synthesis of twenty-two novel benzofuran-isatin-imine hybrids 7a-v tethered through propylene, butylene, pentylene and hexylene, and for the evaluation of their in vitro anti-tubercular and anti-bacterial activities as well as cytotoxicity. All benzofuran-isatin-imine hybrids exhibited considerable in vitro anti-TB (MIC: <0.016-0.218 mu g/mL and 0.062-14.15 mu g/mL against drug-sensitive and MDR MTB, respectively) and anti-bacterial (MIC: 0.25-64 mu g/mL and 0.06-16 mu g/mL against Gram-positive and Gram-negative strains, respectively) activities. All of them also showed acceptable cytotoxicity towards VERO (CC50: 8-128 mu g/mL). The most active hybrid 7j (MIC: <0.016, 0.062 and 0.16 mu g/mL, respectively) was >4.8 and >= 48 folds more potent than the first line anti-TB agents RIF and INH against both drug-sensitive MTB H(37)Rv and MDR-TB isolates, respectively. Moreover, hybrid 7j also demonstrated promising anti-bacterial activities with MIC values of <= 1 mu g/mL against the majority of the tested Gram-negative and Gram-positive pathogens, which was comparable to vancomycin (MIC: 0.5-4 mu g/mL) and CPFX (MIC: 0.125-8 mu g/mL) against Gram-positive bacteria, but slightly less potent than CPFX (MIC: <= 0.03-0.5 mu g/mL) against Gram-negative bacteria. The results indicated that benzofuran-isatin-imine hybrids could act as candidates for the development of anti-TB and anti-bacterial agents. (C) 2019 Elsevier Masson SAS. All rights reserved.