Genc Murat, Karagoz Genc Zuhal, Tekin Suat, Sandal Suleyman, Sirajuddin Muhammad, Hadda Taibi Ben, Sekerci Memet
Acta Chim Slov. 2016 Dec;63(4):726-737. doi: 10.17344/acsi.2016.2428.
This article demonstrates the synthesis of 1,2,4-triazole derivatives and their applications in medicine particularly as anti-breast cancer agents which is a major issue of the present. The synthesized compounds were characterized by elemental analysis, FT-IR and NMR. DFT was used to study the quantum chemical calculations of geometries and vibrational wave numbers of 3-hydroxynaphthyl and p-tolyl substituted 1,2,4-triazoles in the ground state. The scaled harmonic vibrational frequencies obtained from the DFT method were compared with those of the FT-IR spectra and found good agreement. The synthesized 1,2,4-triazole-naphthyl hybrids were screened for the anticancer activity against MCF-7 breast cancer lines. Among them compounds 3 and 7 showed broad spectrum anticancer activity with IC50 values 9.7 μM and 7.10 μM, respectively and their activity is comparable to that of the standard drugs. The molecular model for binding between the compounds (1-8) and the active site of BRCA2 was obtained on the basis of the computational docking results and the structure-activity relationship.
本文展示了1,2,4 - 三唑衍生物的合成及其在医学上的应用，特别是作为抗乳腺癌药物，这是当前的一个主要问题。通过元素分析、傅里叶变换红外光谱（FT - IR）和核磁共振（NMR）对合成的化合物进行了表征。采用密度泛函理论（DFT）研究了3 - 羟基萘基和对甲苯基取代的1,2,4 - 三唑在基态下的几何结构和振动波数的量子化学计算。将从DFT方法获得的标度化谐波振动频率与FT - IR光谱的频率进行比较，发现吻合良好。对合成的1,2,4 - 三唑 - 萘基杂化物针对MCF - 7乳腺癌细胞系进行了抗癌活性筛选。其中化合物3和7表现出广谱抗癌活性，IC50值分别为9.7 μM和7.10 μM，其活性与标准药物相当。基于计算对接结果和构效关系，获得了化合物（1 - 8）与BRCA2活性位点之间结合的分子模型。
