Qudjani Elahe, Iman Maryam, Davood Asghar, Ramandi Mahdi F, Shafiee Abbas
Department of Medicinal Chemistry, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran, Tehran, 19419, Iran.
Recent Pat Anticancer Drug Discov. 2016;11(3):342-51. doi: 10.2174/1574892811666160420141613.
Curcumin is a polyphenolic natural compound with multiple targets that used for the prophylaxis and treatment of some type of cancers like cervical and pancreatic cancers. Some recent patent for curcumin for cancer has also been reviewed.
In this study, ten new curcumin derivatives were designed and synthesized and their cytostatic activity evaluated against the Hela and Panc cell lines that some of them showed more activity than curcumin.
In the present study, a series of mono-carbonyl derivatives of curcumin were designed and prepared. The details of the synthesis and chemical characterization of the synthesized compounds are described. The cytostatic activities of the designed compounds are assessed in two different tumor cell lines using MTT test.
In vitro screening for human cervix carcinoma cell lines (Hela) and pancreatic cell lines (Panc-1) at 24 and 48 hour showed that all the analogs possessed good activity against these tumor cell lines and compounds 5a, 5c and 6 with high potency can be used as a new lead compounds for the designing and finding new and potent cytostatic agents. Docking studies indicated that compound 5c readily binds the active site of human glyoxalase I protein via two strong hydrogen bonds engaging residues of Glu-99 and Lys-156.
Our results are useful in guiding a design of optimized ligands with improved pharmacokinetic properties and increased of anti-cancer activity vs. the prototype curcumin compound.
姜黄素是一种具有多种靶点的多酚类天然化合物，用于预防和治疗某些类型的癌症，如宫颈癌和胰腺癌。最近也对一些姜黄素治疗癌症的专利进行了综述。
本研究设计并合成了10种新的姜黄素衍生物，并评估了它们对Hela和Panc细胞系的细胞生长抑制活性，其中一些衍生物表现出比姜黄素更强的活性。
在本研究中，设计并制备了一系列姜黄素的单羰基衍生物。描述了合成化合物的合成细节和化学表征。使用MTT试验在两种不同的肿瘤细胞系中评估设计化合物的细胞生长抑制活性。
在24小时和48小时对人宫颈癌细胞系（Hela）和胰腺癌细胞系（Panc-1）进行的体外筛选表明，所有类似物对这些肿瘤细胞系均具有良好的活性，化合物5a、5c和6活性高，可作为设计和寻找新型强效细胞生长抑制药物的新先导化合物。对接研究表明，化合物5c通过与Glu-99和Lys-156残基形成的两个强氢键，容易与人乙二醛酶I蛋白的活性位点结合。
我们的结果有助于指导设计具有优化药代动力学性质和增强抗癌活性的配体，相对于原型姜黄素化合物而言。
