Bhale Pravin S, Chavan Hemant V, Dongare Sakharam B, Shringare Sadanand N, Mule Yoginath B, Nagane Samadhan S, Bandgar Babasaheb P
Medicinal Chemistry Research Laboratory, School of Chemical Sciences, Solapur University, Solapur 413 255, Maharashtra, India; Department of Chemistry, Yashwantrao Chavan Mahavidyalaya, Tuljapur, Dist-Osmanabad 413 601, Maharashtra, India.
Department of Chemistry, A.S.P. College, Devrukh, Dist-Ratnagiri 415 804, Maharashtra, India.
Bioorg Med Chem Lett. 2017 Apr 1;27(7):1502-1507. doi: 10.1016/j.bmcl.2017.02.052. Epub 2017 Feb 22.
In the present investigation, synthesis of a series of extended conjugated δ-chloro-α-cyano substituted indolyl chalcones (5a-p) was accomplished by reacting 3-cyanoacetylindole 2 with 3-chloro-3-phenyl-propenal 4 in the presence of piperidine. The structural interpretations of newly synthesized compounds were based on chemical and spectroscopic evidences. Anti-tumor evaluation of the synthesized compounds in vitro against MCF-7 (breast carcinoma) cell line revealed that they possess high anti-tumor activities. Among them, compound 5e and 5a demonstrated excellent activity against breast carcinoma (GI <0.1 and 4μM respectively) as good as adriamycin (GI <0.1μM). The compounds were also screened against the normal Vero monkey cell line, which showed moderate selectivity against inhibition of cancer cells. The effect of extended conjugation on activity authenticated by comparing activity profile of compound 5a, 5i and 5m with their simple analogues. Among the synthesized compounds, 5i and 5l were found to be active anti-inflammatory agents in addition to having noteworthy antioxidant potential. These results suggest the possible use of these compounds for the design and development of novel anti-breast cancer agents.
在本研究中，通过使3-氰基乙酰基吲哚2与3-氯-3-苯基丙烯醛4在哌啶存在下反应，完成了一系列扩展共轭的δ-氯-α-氰基取代吲哚基查耳酮（5a-p）的合成。新合成化合物的结构解析基于化学和光谱证据。对合成化合物进行体外抗MCF-7（乳腺癌）细胞系的抗肿瘤评估表明，它们具有高抗肿瘤活性。其中，化合物5e和5a对乳腺癌表现出优异活性（GI分别<0.1和4μM），与阿霉素（GI<0.1μM）相当。还针对正常Vero猴细胞系对这些化合物进行了筛选，结果显示它们对癌细胞抑制具有适度的选择性。通过比较化合物5a、5i和5m与其简单类似物的活性谱，证实了扩展共轭对活性的影响。在合成化合物中，发现5i和5l除具有显著的抗氧化潜力外，还是活性抗炎剂。这些结果表明这些化合物可能用于设计和开发新型抗乳腺癌药物。
