Journal of Inorganic Biochemistry ( IF 3.8 ) Pub Date : 2022-06-09 , DOI: 10.1016/j.jinorgbio.2022.111900
Debashis Patra 1 , Asmita Pal 2 , Sonali Nath 2 , Rita Kundu 2 , Michael G B Drew 3 , Tapas Ghosh 1
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The basic criteria for the formation of complexes with VO3+, V2O34+ and VO2+ motifs from the VO2+ motif and their interconversion were explored utilizing two multidentate O,N-donor hydrazone ligands namely, E-2-Hydroxy-N′-(4-oxopentan-2-ylidine)benzohydrazide (H3L1) and E-2-Hydroxy-N′-(4-oxo-4-phenylbutan-2-ylidine)benzohydrazide (H3L2), derived from the condensation of 2-hydroxybenzoylhydrazide with acetylacetone and benzoylacetone respectively. Under aerobic condition, the possibility of forming complexes with different motifs in different solvents with varying pH was examined theoretically by computational methods with results that were verified experimentally. This study reveals that under aerobic condition, complexes with VO3+ (1,2) and V2O34+ (3, 4) motifs were formed in protic CH3OH and neutral CHCl3 solvent respectively while the formation of complexes (5–14) with VO2+ motif required protic CH3OH solvent and higher pH (≥ 7). Interconversion of VO3+, V2O34+ and VO2+ motifs are associated with specific acid-base equilibria, substantiated by 51V NMR titrations. Complexes containing these three motifs exhibited promising in vitro anticancer activity in SiHa cervical cancer cells without affecting healthy cells; among them complexes (5–14) with VO2+ motif are more potent. A detailed systematic mechanistic study was carried out, utilizing the two most potent complexes 5 and 6 (IC50 = 13, 6 μM respectively), which indicates that cytotoxicity and anti-proliferative activity of these complexes are manifested through oxidative stress induced apoptotic pathways (caspase mediated).
中文翻译:

深入了解 VO2+ 基序向 VO3+、V2O34+ 和 VO2+ 基序的转化及其相互转换以及它们在 SiHa 宫颈癌细胞中的抗癌活性的详细机制研究
利用两个多齿O,N-供体腙配体,即E-2,探索了由VO 2+基序与VO 3+、V 2 O 3 4+和VO 2 +基序形成复合物及其相互转化的基本标准-羟基-N'-(4-oxopentan-2-ylidine)benzohydrazide (H 3 L 1 ) 和 E-2-Hydroxy-N'-(4-oxo-4-phenylbutan-2-ylidine)benzohydrazide (H 3 L 2),衍生自 2-羟基苯甲酰肼分别与乙酰丙酮和苯甲酰丙酮缩合。在有氧条件下,通过计算方法从理论上检验了在不同 pH 值的不同溶剂中形成具有不同基序的复合物的可能性,并通过实验验证了结果。本研究表明,在有氧条件下,在质子CH 3 OH和中性CHCl 3溶剂中分别形成VO 3+ ( 1 , 2 )和V 2 O 3 4+ ( 3 , 4 )基序的络合物,而络合物( 5 – 14) VO 2 +基序需要质子 CH 3 OH 溶剂和更高的 pH 值 (≥ 7)。VO 3+、V 2 O 3 4+和VO 2 +基序的相互转换与特定的酸碱平衡有关,这由51 V NMR 滴定得到证实。含有这三个基序的复合物在 SiHa 宫颈癌细胞中表现出有希望的体外抗癌活性,而不影响健康细胞;其中具有 VO 2 +基序的复合物 ( 5 – 14 )更有效。利用两种最有效的复合物5进行了详细的系统机理研究和6(IC 50 = 13, 6 μM),这表明这些复合物的细胞毒性和抗增殖活性通过氧化应激诱导的凋亡途径(半胱天冬酶介导)表现出来。