Synthesis, Cytotoxicity and Antimicrobial Action of 11 Analogs of Nifuroxazide.

The global spread of multidrug-resistant bacteria, alongside the rising burden of oncological diseases, poses an increasing threat to human health and public healthcare systems worldwide. Substantial efforts are underway to discover new drugs and to reposition or repurpose existing ones. Recently, nifuroxazide introduced into clinical practice in the late 1960s has attracted considerable attention due to its antitumor potential. However, its poor absorption in the intestinal tract limits its applicability as a systemic antitumor agent, a limitation that can be addressed through chemical modification. In this study, we evaluated 11 nifuroxazide analogs featuring systematic modifications to both the five-membered ring (replacement of furan with thiophene) and the six-membered aromatic ring (variation in the position and nature of substituents). MTT cytotoxicity assays performed on HCT116 and HEK293 cell lines revealed that 5-nitrofurfurylidene hydrazide of 2-pyridinecarboxylic acid and 5-nitrothien-2-yl hydrazide of 2-pyridinecarboxylic acid exhibit selective toxicity toward tumor cells while showing significantly lower toxicity to non-tumor cells, indicating potential for further investigation in more complex biological models. Antimicrobial activity testing identified 5-nitrofurfurylidene hydrazide of 3-hydroxybenzoic acid and 5-nitrofurfurylidene hydrazide of 3-pyridinecarboxylic acid as particularly potent.