Synthesis of Chromeno[2,3-c]Pyrazol-(2H)-one Derivatives: A New Class of Antibacterial and Antifungal Agents.

In 2024, vector-borne diseases and fungal infections caused millions of deaths worldwide, despite the availability of existing treatments (World Health Organization). These alarming statistics highlight the need for new bioactive compounds with strong microbial activity. In this context, we designed a novel series of chromeno[2,3-c]pyrazol-(2H)-one derivatives, incorporating the coumarin scaffold, known for its broad biological activities, and the pyrazole moiety, recognized for its pharmacological potential. The synthesis followed a three-step protocol, yielding 14 new analogs with good yields (56%-94%). Structural characterization was performed through extensive nuclear magnetic resonance spectroscopy, including one-dimensional (1H and 13C) and two-dimensional (heteronuclear single-quantum correlation, heteronuclear multiple bond correlation, and correlated spectroscopy) techniques. Antimicrobial evaluations revealed that several derivatives against both drug-susceptible and resistant strains of Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 29213, and Bacillus cereus ATCC 10876, and a clinical isolate of Candida albicans. Notably, compound 3j demonstrated potent broad-spectrum activity, with bactericidal and fungicidal properties supported by minimum inhibitory concentration (58-458 µg/mL) and minimum bactericidal concentration/minimum fungicidal concentration (< 4) values. Compound 1 also showed exceptional fungicidal action, surpassing fluconazole with an activity index near 100%. Structure-activity relationship analysis revealed that electron-withdrawing and hydrophobic substitutions significantly enhanced antimicrobial potency. Overall, these findings highlight chromeno[2,3-c]pyrazol-(2H)-ones emerge as a promising candidate for next-generation anti-infective drug development.