Hidden potential of hydrazinecarboxamides (semicarbazides) as potential antimicrobial agents: A review
Martin Krátký1, Neto-Honorius Houngbedji1, Jarmila Vinšová1
1Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 500 03 Hradec Králové, Czech Republic.
Abstract:
Hydrazinecarboxamides (semicarbazides) are increasingly recognized as a versatile scaffold in developing potential antimicrobial agents. In addition to a brief overview of the synthetic methods to prepare them, this review comprehensively analyses their antimicrobial properties. These derivatives have demonstrated potent activity against a broad spectrum of mycobacteria, bacterial and fungal pathogens, highlighting their potential to address critical human health challenges, including neglected diseases, and to combat growing antimicrobial resistance. They have also been investigated for their antiviral and antiparasitic properties. The review also summarizes structure-activity relationships, known mechanisms of action and emphasizes the crucial role of the hydrazinecarboxamide moiety in facilitating interactions with biological targets. The combination of hydrazinecarboxamides with other bioactive scaffolds (primaquine, isoniazid, etc.) has led to an identification of promising drug candidates, including those active against resistant strains, offering a promising approach for future innovations in the field of antimicrobial therapy. Attention is also drawn to limitations of hydrazinecarboxamides (poor physicochemical properties, cytotoxicity to human cells, and insufficient target selectivity), which may hinder their clinical application.
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