Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 500 03 Hradec Králové, Czech Republic.
Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 500 03 Hradec Králové, Czech Republic.
Biomed Pharmacother. 2024 Nov;180:117556. doi: 10.1016/j.biopha.2024.117556. Epub 2024 Oct 14.
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.
肼基甲酰胺（氨基脲）作为一种多功能支架，在开发有潜力的抗菌药物方面越来越受到关注。除了简要概述其合成方法外，本综述还全面分析了它们的抗菌特性。这些衍生物对广泛的分枝杆菌、细菌和真菌病原体表现出很强的活性，凸显了它们在解决包括被忽视疾病在内的重大人类健康挑战以及应对日益增长的抗菌药物耐药性方面的潜力。它们还被研究了其抗病毒和抗寄生虫特性。综述还总结了构效关系、已知的作用机制，并强调了肼基甲酰胺部分在促进与生物靶标相互作用方面的关键作用。肼基甲酰胺与其他生物活性支架（伯氨喹、异烟肼等）的结合已经确定了有前途的候选药物，包括对耐药菌株有效的药物，为抗菌治疗领域的未来创新提供了有希望的方法。还提请注意肼基甲酰胺的局限性（较差的物理化学性质、对人细胞的细胞毒性和靶标选择性不足），这可能会阻碍其临床应用。
