Synthesis, Antimicrobial, and Anticancer Activities of Novel Nitrofuran Derivatives

Keeping in view the varying therapeutic attributes of 5-nitrofuran and isatin derivatives, novel 5-nitrofuran-isatin molecular hybrids (2, 5-7) were synthesized by standard protocols, characterized by various spectroscopic techniques, and eventually evaluated against a group of pathogenic bacteria and fungi. Greater potency against Methicillin-resistant Staphylococcus aureus (MRSA) was exhibited by hybrids 5 and 6 with minimum inhibitory concentration values of 8 and 1 mu g/mL, respectively. Cytotoxicity against both human embryonic kidney cells (HEK-293) and human red blood cells (RBCs) was investigated for the hybrids in hand. All hybrids appeared to have good safety; all of them were devoid of cytotoxicity, and none displayed hemolytic activity at the highest test concentration (CC50 and HI10 > 32 mu g/mL). To support the postulation that these hybrids would be analogous to drugs containing the 5-nitrofurn ring system, molecular docking was carried out to streamline the binding affinity of the investigated hybrids towards the E. coli nitroreductase (NTR). Compared to the standard drug nitrofurazone, hybrid 6 demonstrated a higher affinity and better binding interactions with the NTR binding pocket. Therefore, it could be concluded that 6 displays its antibacterial action through a mechanism similar to that of nitrofurazone. Nonetheless, further wet investigations are to be conducted to confirm this finding. Encouraged by the well-established anticancer activity of isatin derivatives, 2, 5-7 were assessed for their potential antitumor activity, and they well demonstrated potent inhibitory activity against the human colon cancer cell line HCT 116 (IC50 = 1.62-8.8 mu M) with isatin hybrid 3 being the best (IC50 = 1.62 mu M). Thus, it is herein reported that these 5-nitrofuran-isatin molecular hybrids could represent an ideal starting point for future studies to develop potent antimicrobial agents.