Two new secophragmalin-type limonoids, secotrichagmalins B (1) and C (2) along with two known compounds, were isolated from the fruits of Trichilia connaroides. The structures of the new compounds were elucidated by analysis of spectroscopic (IR, MS, and 2D NMR) data and single crystal X-ray diffraction studies. In addition, semisynthetic derivatives (2a-2l) were efficiently synthesized and evaluated for their in vitro cytotoxicity along with the isolated limonoids against a panel of human cancer cell lines. The results indicated that new analogues 2a, 2d, and 2e showed cytotoxicity on the DU145 cell line with IC50 values of 3.6, 4.2, and 5.2 μM, respectively. Flow cytometric analysis revealed that these analogues arrested the cell cycle in the G0/G1 phase and markedly induced apoptosis.