Abstract

A molecular hybridization of natural products is a new concept in drug discovery and having critical roles to design new molecules with improved biological properties. Hybrid molecules display higher biological activities when compared to the parent drugs. In the present study, two natural products (thymol and artemisinin (ART)) are used for the synthesis of new hybrid thymol-artemisinin. After characterization, the cytotoxic activity of ART-thymol was tested against different cancer cell lines and non-cancerous human cell line. ART-Thymol show the cytotoxic effect with EC₅₀ values 70,96μM for HepG2, 97,31μM for LnCap, 6,03μM for Caco-2, 77,98μM for HeLa and 62,28μM for HEK293 cells, respectively. Moreover, ART-Thymol was checked for drug-likeness, and the kinase inhibitory activity. ART-Thymol is investigated by using molecular docking. The results of qPCR was indicated CDK2 and P38 were inhibited by ART-Thymol. These results improved that thymol-artemisinin may be new candidates as an anticancer agents.

摘要

天然产物的分子杂交是药物开发中的一个新概念，在设计具有改善的生物学特性的新分子方面起着关键作用。与母体药物相比，杂合分子表现出更高的生物活性。在本研究中，两种天然产物（百里香酚和青蒿素（ART））被用于合成新的杂交百里香酚-青蒿素。表征后，测试了ART-百里酚对不同癌细胞系和非癌性人类细胞系的细胞毒活性。ART-百里酚显示出细胞毒性作用，HepG2的EC ₅₀值分别为70,96μM，LnCap的97.31μM，Caco-2的6.03μM，HeLa的77.98μM和HEK293细胞的62.28μM。此外，ART-百里酚检查药物样貌和激酶抑制活性。通过分子对接研究了百里香酚。qPCR结果表明ART-Thymol抑制CDK2和P38的表达。这些结果改善了百里酚青蒿素可能作为抗癌药的新候选者。