Diverted total synthesis of melodorinol analogues and evaluation of their cytotoxicity

Link: https://www.sciencedirect.com/science/article/pii/S0040403918307342

Title: Diverted total synthesis of melodorinol analogues and evaluation of their cytotoxicity

Authors: Tanatorn Khotavivattana,* Thitiphong Khamkhenshorngphanuch, Kitiya Rassamee, Pongpun Siripong, Tirayut Vilaivan

Abstract:  A series of melodorinol analogues were synthesized via a diverted total synthesis approach, leading to structural modifications on several regions of the molecule. Their cytotoxicity was evaluated against five human cancer cell lines (KB, HeLa-S3, MCF-7, HT-29 and A549). Structure-activity relationship studies revealed key parameters that affect the cytotoxicity. In particular, the novel 4-bromo-furanone analogues exhibited greater cytotoxicity compared to the corresponding non-brominated analogues. The stereochemistry at C-6 and the nature of acyl substituents on the C-6 and C-7 hydroxyl groups also play an important role. The most potent analogues exhibit approximately 15-fold higher cytotoxicity towards KB and HeLa-S3 than melodorinol and also show exceptionally high potency against MCF-7, HT-29 and A549 cell lines.

Cite this: Khotavivattana, T.; Khamkhenshorngphanuch, T.; Rassamee, K.; Siripong, P.; Vilaivan, T. Diverted total synthesis of melodorinol analogues and evaluation of their cytotoxicity. Tetrahedron Lett. 2018, 59, 2711-2715.