Mabkhot Yahia Nasser, Barakat Assem, Yousuf Sammer, Choudhary M Iqbal, Frey Wolfgang, Ben Hadda Taibi, Mubarak Mohammad S
Department of Chemistry, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia.
Department of Chemistry, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia; Department of Chemistry, Faculty of Science, Alexandria University, PO Box 426, Ibrahimia, Alexandria 21321, Egypt.
Bioorg Med Chem. 2014 Dec 1;22(23):6715-6725. doi: 10.1016/j.bmc.2014.08.014. Epub 2014 Aug 20.
A series of 15 novel compounds incorporating the thieno[2,3-b]thiophene moiety were synthesized. The chemical structures of these compounds were deduced from elemental analyses, (1)H NMR, (13)C NMR, and ESI-mass spectral data. The enzyme inhibition potential of these compounds was evaluated, in vitro, against β-glucuronidase, xanthine oxidase, and α-chymotrypsin enzymes. The cytotoxicity was evaluated by a cell viability assay utilizing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye. Among the compounds tested, compound 3 was the most potent β-glucuronidase inhibitor with an IC50 value of 0.9 ± 0.0138 μM; it was much more active than the standard, d-saccharic acid 1,4-lactone (IC50=45.75 ± 2.16 μM). Compound 12, on the other hand, was the most potent as a xanthine oxidase inhibitor with an IC50 of 14.4 ± 1.2 μM. With the characterization of their mechanism of action and with further testing, these compounds could be useful candidates as anticancer drugs. In addition, the newly synthesized compounds were subjected to POM analyses to get insights about their degree of their toxicity.
合成了一系列包含噻吩并[2,3 - b]噻吩部分的15种新型化合物。这些化合物的化学结构通过元素分析、¹H NMR、¹³C NMR和ESI - 质谱数据推导得出。在体外评估了这些化合物对β - 葡萄糖醛酸酶、黄嘌呤氧化酶和α - 胰凝乳蛋白酶的酶抑制潜力。通过使用3 - (4,5 - 二甲基噻唑 - 2 - 基)-2,5 - 二苯基四氮唑溴盐(MTT)染料的细胞活力测定法评估细胞毒性。在所测试的化合物中，化合物3是最有效的β - 葡萄糖醛酸酶抑制剂，IC50值为0.9±0.0138μM；它比标准品d - 糖二酸1,4 - 内酯(IC50 = 45.75±2.16μM)活性高得多。另一方面，化合物12作为黄嘌呤氧化酶抑制剂最有效，IC50为14.4±1.2μM。随着其作用机制的表征和进一步测试，这些化合物可能是有用的抗癌药物候选物。此外，对新合成的化合物进行偏光显微镜(POM)分析以了解其毒性程度。
