Centre for Nano and Material Sciences, Jain University, Jain Global Campus, Bengaluru 562112, Karnataka, India.
Biophysical Chemistry Laboratory, Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia (A Central University), New Delhi 110025, India.
Eur J Pharm Sci. 2018 Oct 15;123:335-349. doi: 10.1016/j.ejps.2018.07.008. Epub 2018 Jul 5.
In the efforts to develop a biocompatible transition metal complex as a drug alike for some of the prevailing non-communicable diseases (NCDs) and communicable diseases (CDs), a novel binuclear Ni compound [{Ni(hpdbal-sbdt)}] (2) has been synthesized by the reaction of Ni(OAc).4HO and Hhpdbal-sbdt (1) [1 is a dibasic tridentate ONS donor Schiff base ligand obtained by the condensation of 2-hydroxy-5-(phenyldiazenyl)benzaldehyde (Hhpdbal) and S-benzyldithiocarbazate (Hsbdt)]. Both ligand 1 and compound 2 were structurally characterized in the solid and solution state using various spectroscopic techniques like ATIR, H NMR, C NMR, TGA, FESEM, EDS and CHNS analysis. The antidiabetic activity of Hhpdbal-sbdt (1) and [{Ni(hpdbal-sbdt)}] (2) were assessed using 2-NBDG uptake assay. The assay results showed 85% and 95% of fluorescent glucose uptake by insulin resistant HePG2 cells treated with compounds 1 and 2 respectively. The 2-NBDG uptake by the cells treated with the compound 2 was observed to be comparable to the standard antidiabetic drug metformin. Compounds 1 and 2 were also tested against five bacterial and two fungi strains in order to evaluate pathogen killing activity. Compound 2 showed significant inhibitory action towards the methicillin-resistant Staphylococcus aureus (MRSA) strain with an MIC value of 2 μg/mL whereas the ligand 1 was found to be inactive. Furthermore, the interactive nature of compound 2 with a model serum carrier protein bovine serum albumin (BSA) was studied using a multi-spectroscopic approach which provided an insight into the nature and extent of binding, conformational changes and the quenching of amino acid residues of the protein.
在开发一种类似药物的生物兼容过渡金属配合物以治疗一些流行的非传染性疾病 (NCDs) 和传染性疾病 (CDs) 的努力中，通过 Ni(OAc).4HO 和 Hhpdbal-sbdt (1) 的反应合成了一种新型双核 Ni 化合物 [{Ni(hpdbal-sbdt)}] (2) [1 是一种双碱性三齿 ON 供体希夫碱配体，由 2-羟基-5-(苯基亚氨基)苯甲醛 (Hhpdbal) 和 S-苄基二硫代氨基甲酸盐 (Hsbdt) 的缩合反应得到]。在固态和溶液态中，使用各种光谱技术（如 ATIR、H NMR、C NMR、TGA、FESEM、EDS 和 CHNS 分析）对配体 1 和化合物 2 进行了结构表征。使用 2-NBDG 摄取测定法评估了 Hhpdbal-sbdt (1) 和 [{Ni(hpdbal-sbdt)}] (2) 的抗糖尿病活性。测定结果表明，胰岛素抵抗的 HePG2 细胞用化合物 1 和 2 处理后，荧光葡萄糖摄取率分别为 85%和 95%。用化合物 2 处理的细胞的 2-NBDG 摄取量与标准抗糖尿病药物二甲双胍相当。还对 5 种细菌和 2 种真菌株进行了化合物 1 和 2 的测试，以评估病原体杀伤活性。化合物 2 对耐甲氧西林金黄色葡萄球菌 (MRSA) 菌株表现出显著的抑制作用，MIC 值为 2μg/mL，而配体 1 则无活性。此外，还使用多光谱方法研究了化合物 2 与模型血清载体蛋白牛血清白蛋白 (BSA) 的相互作用性质，从而深入了解了结合的性质和程度、构象变化以及蛋白质氨基酸残基的猝灭。
