Mabkhot Yahia Nasser, Barakat Assem, Al-Majid Abdullah Mohammed, Alshahrani Saeed, Yousuf Sammer, Choudhary M Iqbal
Department of Chemistry, Faculty of Science, King Saud University, P, O, Box 2455, Riyadh 11451, Saudi Arabia.
Chem Cent J. 2013 Jul 8;7(1):112. doi: 10.1186/1752-153X-7-112.
The derivatives of thieno[2,3-b]thiophene belong to a significant category of heterocyclic compounds, which have shown a wide spectrum of medical and industrial application.
A new building block with two electrophilic center of thieno[2,3-b]thiophene derivatives 2 has been reported by one-pot reaction of diketone derivative 1 with Br2/AcOH in excellent yield. A variety of heteroaromatics having bis(1H-imidazo[1,2a] benzimidazole), bis(1H-imidazo[1,2-b][1,2,4]triazole)-3-methyl-4-phenylthieno[2,3-b]thiophene derivatives, dioxazolo-, dithiazolo-, and 1H-imidazolo-3-methyl-4-phenylthieno[2,3-b]thiophene derivatives as well pyrrolo, thiazolo -3-methyl-4-phenylthieno[2,3-b]thiophene derivatives have been designed, synthesized, characterized, and evaluated for their biological activity. Compounds 3-9 showed good bioassay result. These new derivatives were evaluated for anti-cancer activity against PC-3 cell lines, in vitro antioxidant potential and β-glucuronidase and α-glucosidase inhibitory activities. Compound 3 (IC50 = 56.26 ± 3.18 μM) showed a potent DPPH radical scavenging antioxidant activity and found to be more active than standard N-acetylcystein (IC50 = 105.9 ± 1.1 μM). Compounds 8a (IC50 = 13.2 ± 0.34 μM) and 8b (IC50 = 14.1 ± 0.28 μM) found as potent inhibitor of α-glucusidase several fold more active than the standard acarbose (IC50 = 841 ± 1.73 μM). Most promising results were obtained in β-glucuronidase enzyme inhibition assay. Compounds 5 (IC50 = 0.13 ± 0.019 μM), 6 (IC50 = 19.9 ± 0.285 μM), 8a (IC50 = 1.2 ± 0.0785 μM) and 9 (IC50 = 0.003 ± 0.09 μM) showed a potent inhibition of β-glucuronidase. Compound 9 was found to be several hundred fold more active than standard D-Saccharic acid 1,4-lactone (IC50 = 45.75 ± 2.16 μM).
Synthesis, characterization, and in vitro biological activity of a series of thieno[2,3-b]thiophene have been investigated.
噻吩并[2,3 - b]噻吩衍生物属于一类重要的杂环化合物，已显示出广泛的医学和工业应用。
通过二酮衍生物1与Br2/AcOH的一锅反应，以优异的产率报道了一种具有两个亲电中心的噻吩并[2,3 - b]噻吩衍生物2的新构建单元。设计、合成、表征并评估了多种具有双（1H - 咪唑并[1,2 - a]苯并咪唑）、双（1H - 咪唑并[1,2 - b][1,2,4]三唑）-3 - 甲基 - 4 - 苯基噻吩并[2,3 - b]噻吩衍生物、二恶唑并、二噻唑并和1H - 咪唑并 - 3 - 甲基 - 4 - 苯基噻吩并[2,3 - b]噻吩衍生物以及吡咯并、噻唑并 - 3 - 甲基 - 4 - 苯基噻吩并[2,3 - b]噻吩衍生物的杂芳烃的生物活性。化合物3 - 9显示出良好的生物测定结果。对这些新衍生物进行了针对PC - 3细胞系的抗癌活性、体外抗氧化潜力以及β - 葡萄糖醛酸酶和α - 葡萄糖苷酶抑制活性的评估。化合物3（IC50 = 56.26 ± 3.18 μM）表现出有效的DPPH自由基清除抗氧化活性，并且发现其比标准的N - 乙酰半胱氨酸（IC50 = 105.9 ± 1.1 μM）更具活性。化合物8a（IC50 = 13.2 ± 0.34 μM）和8b（IC50 = 14.1 ± 0.28 μM）被发现是α - 葡萄糖苷酶的有效抑制剂，其活性比标准的阿卡波糖（IC50 = 841 ± 1.73 μM）高几倍。在β - 葡萄糖醛酸酶抑制试验中获得了最有前景的结果。化合物5（IC50 = 0.13 ± 0.019 μM）、6（IC50 = 19.9 ± 0.285 μM）、8a（IC50 = 1.2 ± 0.0785 μM）和9（IC50 = 0.003 ± 0.09 μM）表现出对β - 葡萄糖醛酸酶的有效抑制。发现化合物9的活性比标准的D - 糖二酸1,4 - 内酯（IC5 = 45.75 ± 2.16 μM）高几百倍。
研究了一系列噻吩并[2,3 - b]噻吩的合成
