Phragmalin-type limonoid orthoesters from the twigs and leaves of Khaya ivorensis and their cytotoxic activities

Abstract

Nine previously unreported phragmalin-type limonoid orthoesters, named ivorenoids G–O (1–9), together with seventeen known analogues (10–26) were isolated from the twigs and leaves of Khaya ivorensis. Their structures, including absolute configurations, were determined by extensive spectroscopic analyses, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Selected compounds were evaluated for cytotoxicity against five human cancer cell lines (HL-60, A-549, SMMC-7721, MCF-7, and SW480), and their structure–activity relationships were systematically analyzed. Notably, compound 15 exhibited cytotoxicity against A549 and SMMC-7721 cell lines, with IC₅₀ values of 14.0 ± 0.4 μM and 14.9 ± 0.6 μM, respectively. Compound 22 showed cytotoxicity against SW480 cells, with an IC₅₀ value of 7.5 ± 0.2 μM, while compound 25 displayed cytotoxicity against A549 cells, with an IC₅₀ of 14.6 ± 1.9 μM. These findings highlight the potential of limonoid orthesters derived from K. ivorensis as promising lead compounds for further anticancer drug development.