Aliabadi Alireza, Mohammadi-Farani Ahmad, Roodabeh Sahar, Ahmadi Farahnaz
Pharmaceutical Sciences Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Iran J Pharm Res. 2017 Winter;16(1):165-172.
In the recent years, the role of LOX enzymes in the origin of neoplastic diseases such as colorectal, skin, pancreatic and renal cancers has been confirmed. A new series of 1,3,4-thiadiazole derivatives bearing 2-pyridyl moiety was synthesized and the cytotoxicity of the members of this series was assessed using MTT protocol. Enzyme inhibitory activity of the prepared compounds was also tested against 15-lipoxygenase-1 as a novel target for the discovery of anticancer drugs. PC3, HT29 and SKNMC cell lines were utilized and the obtained results were compared with doxorubicin. Overall, nitro containing derivatives exerted a higher cytotoxic activity against PC3 cell line and methoxylated derivatives showed an acceptable activity against SKNMC cell line. Methoxylated derivatives were also the most potent enzyme inhibitors especially at position of the phenyl residue.
近年来，赖氨氧化酶（LOX）在诸如结直肠癌、皮肤癌、胰腺癌和肾癌等肿瘤性疾病起源中的作用已得到证实。合成了一系列带有2-吡啶基部分的新型1,3,4-噻二唑衍生物，并使用MTT法评估了该系列成员的细胞毒性。还针对15-脂氧合酶-1作为发现抗癌药物的新靶点测试了所制备化合物的酶抑制活性。利用了PC3、HT29和SKNMC细胞系，并将所得结果与阿霉素进行比较。总体而言，含硝基的衍生物对PC3细胞系具有更高的细胞毒性活性，而甲氧基化衍生物对SKNMC细胞系显示出可接受的活性。甲氧基化衍生物也是最有效的酶抑制剂，尤其是在苯基残基的位置。
