A series of schisantherin A (1) derivatives were efficiently synthesized utilizing Yamaguchi esterification (2, 4, 6-trichlorobenzoyl chloride, Et3N, THF, DMAP, Toluene) at the C-7' position of the schisantherin A core. The synthesized derivatives were evaluated for their anti-cancer activities against SIHA, PANC 1, MDA-MB-231, IMR-32, DU-145, and A-549 cancer cell lines using sulphorodamine B assay. Within the new series tested, compound 29 displayed most promising cytotoxic effect against human cervical cancer cell line (SIHA) with GI50 value of <0.01µM, which is comparable to the standard drug, doxorubicin. Mechanism of action studies validated that 29 functions as a microtubule inhibitor. Additionally, several of the other analogues exhibited potent activity against the tested cell lines. Based on the results obtained structure activity relationship (SAR) were established and a correlation between the activities was also observed and discussed.