Saleem Muhammad, Hanif Muhammad, Rafiq Muhammad, Hassan Mubashir, Tahir Tehreem
Department of Chemistry, University of Sargodha, Sargodha, Pakistan.
Department of Chemistry, Thal University Bhakkar, 30000, Bhakkar, Pakistan.
J Fluoresc. 2023 Jan;33(1):113-124. doi: 10.1007/s10895-022-03032-y. Epub 2022 Oct 25.
Recently, screening of efficient urease inhibitors by employing organic small molecules metalloderivatives interests the scientific community due to their efficacy for treatment of urease triggered health complications. This study comprises the synthesis, urease inhibition activity, optical analysis and molecular modeling of hydrazinecarbothioamide and hydrazinecarboxamide metalloderivatives. Characterization of synthesized materials was done by UV-visible, fluorescence, NMR and FTIR spectroscopic analysis. Metalloderivatization of ligands induce increment in urease inhibition potential and effect was prominent for copper complexes with 10-fold enhancement, cobalt complex with 3.5 fold's enhancement and palladium with 2-fold increment in the inhibition efficacy toward urease when it was compared with reference urease inhibitor. Zinc and iron complexes cause declined urease inhibition activity of the bare ligand. The overall activity of hydrazinecarbothioamide slightly exceeds than that of hydrazinecarboxamide, possibly due to larger complexation ability of sulfur-based ligand in comparison to oxygenated derivatives i.e., hydrazinecarboxamide. The enzyme inhibition kinetics for the most active complexes represent the mixed type urease inhibition for 3a and competitive urease inhibition for 5a, as determined by Lineweaver-Burk plots. The docked scoring values for both the ligands were calculated to be 61.34, 64.72, 56.68, 62.94, 64.98 and 58.98. Three active hydrogen bonds were observed in docking complex upon computational analysis of most potent metallodrug 3a inside active region of targeted protein.
最近，利用有机小分子金属衍生物筛选高效脲酶抑制剂引起了科学界的兴趣，因为它们对治疗脲酶引发的健康并发症具有疗效。本研究包括肼基硫代甲酰胺和肼基甲酰胺金属衍生物的合成、脲酶抑制活性、光学分析和分子建模。通过紫外可见、荧光、核磁共振和傅里叶变换红外光谱分析对合成材料进行了表征。配体的金属衍生化导致脲酶抑制潜力增加，与参考脲酶抑制剂相比，铜配合物的抑制效果显著增强10倍，钴配合物增强3.5倍，钯配合物的抑制效果增强2倍。锌和铁配合物导致裸配体的脲酶抑制活性下降。肼基硫代甲酰胺的总体活性略高于肼基甲酰胺，这可能是由于硫基配体比含氧衍生物（即肼基甲酰胺）具有更大的络合能力。通过Lineweaver-Burk图确定，活性最高的配合物的酶抑制动力学代表3a为混合型脲酶抑制，5a为竞争性脲酶抑制。两种配体的对接评分值分别计算为61.34、64.72、56.68、62.94、64.98和58.98。在对靶向蛋白活性区域内最有效的金属药物3a进行计算分析时，对接复合物中观察到三个活性氢键。
