Hryhoriv Halyna, Kovalenko Sergiy M, Georgiyants Marine, Sidorenko Lyudmila, Georgiyants Victoriya
Pharmaceutical Chemistry Department, National University of Pharmacy, 61002 Kharkiv, Ukraine.
Organic Chemistry Department, Karazin National University, 61022 Kharkiv, Ukraine.
Antibiotics (Basel). 2023 Mar 21;12(3):625. doi: 10.3390/antibiotics12030625.
Fluoroquinolones have been studied for more than half a century. Since the 1960s, four generations of these synthetic antibiotics have been created and successfully introduced into clinical practice. However, they are still of interest for medicinal chemistry due to the wide possibilities for chemical modification, with subsequent useful changes in the pharmacokinetics and pharmacodynamics of the initial molecules. This review summarizes the chemical and pharmacological results of fluoroquinolones hybridization by introducing different heterocyclic moieties into position 3 of the core system. It analyses the synthetic procedures and approaches to the formation of heterocycles from the fluoroquinolone carboxyl group and reveals the most convenient ways for such procedures. Further, the results of biological activity investigations for the obtained hybrid pharmacophore systems are presented. The latter revealed numerous promising molecules that can be further studied to overcome the problem of resistance to antibiotics, to find novel anticancer agents and more.
氟喹诺酮类药物已经被研究了半个多世纪。自20世纪60年代以来，已经研发出四代这类合成抗生素，并成功应用于临床实践。然而，由于其在化学修饰方面具有广泛的可能性，能够对初始分子的药代动力学和药效学产生有益的后续变化，因此它们仍然是药物化学领域的研究热点。本综述总结了通过在核心体系的3位引入不同杂环部分实现氟喹诺酮类药物杂化的化学和药理学成果。分析了从氟喹诺酮羧基形成杂环的合成方法和途径，并揭示了此类过程最便捷的方法。此外，还介绍了所获得的杂化药效团系统的生物活性研究结果。后者揭示了众多有前景的分子，可进一步研究以克服抗生素耐药性问题、寻找新型抗癌药物等等。
