Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Sezione Chimica Farmaceutica e Biologica, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
ChemMedChem. 2011 Jul 4;6(7):1300-9. doi: 10.1002/cmdc.201100078. Epub 2011 Apr 26.
Given the potent antimicrobial, antiviral, and antitumor activities of many natural products, there is an increasing interest in the synthesis of new molecules based on natural compound scaffolds. Based on a 2,4-bis(3'-indolyl)imidazole skeleton, two new series of phenylthiazolylindoles and phenylthiazolyl-7-azaindoles were obtained by Hantzsch reaction between substituted phenylthioamides and the α-bromoacetyl derivatives. Some azaindole derivatives, tested at the National Cancer Institute against a panel of ∼60 tumor cell lines derived from nine human cancer cell types, showed inhibitory effects against all cell lines investigated at micromolar to nanomolar concentrations. Two of them exhibited a high affinity for CDK1, with IC(50) values of 0.41 and 0.85 μM. These promising results will set the foundation for future investigations into the development of anticancer therapies.
鉴于许多天然产物具有强大的抗菌、抗病毒和抗肿瘤活性，人们越来越感兴趣地根据天然化合物支架来合成新的分子。以 2,4-双（3'-吲哚基）咪唑骨架为基础，通过取代的苯硫酰胺与α-溴代乙酰基衍生物之间的 Hantzsch 反应，得到了两个新的苯并噻唑基吲哚和苯并噻唑基-7-氮杂吲哚系列。一些氮杂吲哚衍生物在国家癌症研究所进行了测试，针对来自九种人类癌细胞类型的约 60 种肿瘤细胞系进行了测试，在微摩尔至纳摩尔浓度下对所有测试的细胞系均显示出抑制作用。其中两种对 CDK1 具有高亲和力，IC（50）值分别为 0.41 和 0.85 μM。这些有希望的结果将为未来开发抗癌疗法的研究奠定基础。
