Dar Ovas Ahmad, Lone Shabir Ahmad, Malik Manzoor Ahmad, Aqlan Faisal Mohammed, Wani Mohmmad Younus, Hashmi Athar Adil, Ahmad Aijaz
Department of Chemistry, Jamia Millia Islamia, New Delhi 110025, India.
Clinical Microbiology and Infectious Diseases, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa.
Heliyon. 2019 Jul 17;5(7):e02055. doi: 10.1016/j.heliyon.2019.e02055. eCollection 2019 Jul.
Metal based drugs are important class of chemotherapeutic agents that have the potential to circumvent drug resistance. Increasing drug resistance, treatment failures and limited treatment options necessitates the development of new therapeutic drugs with different mechanisms of action. Towards this direction, we synthesized a series of isatin based mixed ligand complexes of [Cu(dbm)LClHO] , [Co(dbm)LCl] and [Ni(dbm)LClHO] and evaluated their antifungal activity alone and in combination with fluconazole (FLC) against seven different isolates. The insight mechanism of antifungal action was revealed by studying apoptosis via terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. The study revealed that all these compounds showed antifungal activity at varying concentrations with as the most potent compound with minimum inhibitory concentration ranging from 0.5-8 μg/mL and minimum fungicidal concentration ranging from 4-16 μg/mL. Upon combination with FLC, most of the interactions were either synergistic (54 %) or additive (32 %) with no antagonistic combination against any of the tested isolate. The study on their mechanism of action revealed that these compounds show apoptotic effect on at sub-inhibitory concentrations, suggesting that strategies to target this process may augment the current antifungal treatment modalities.
金属基药物是一类重要的化疗药物，具有克服耐药性的潜力。耐药性增加、治疗失败以及治疗选择有限，使得开发具有不同作用机制的新型治疗药物成为必要。朝着这个方向，我们合成了一系列基于异吲哚酮的混合配体配合物[Cu(dbm)LClHO]、[Co(dbm)LCl]和[Ni(dbm)LClHO]，并单独以及与氟康唑（FLC）联合评估了它们对七种不同分离株的抗真菌活性。通过末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）试验研究细胞凋亡，揭示了抗真菌作用的内在机制。研究表明，所有这些化合物在不同浓度下均表现出抗真菌活性，其中[具体化合物名称未给出]是最有效的化合物，其最低抑菌浓度范围为0.5 - 8μg/mL，最低杀菌浓度范围为4 - 16μg/mL。与FLC联合使用时，大多数相互作用要么是协同的（54%），要么是相加的（32%），对任何测试分离株均无拮抗组合。对其作用机制的研究表明，这些化合物在亚抑菌浓度下对[具体细胞名称未给出]表现出凋亡效应，这表明针对该过程的策略可能会增强当前的抗真菌治疗方式。
