In vitro anticancer potential of lapachol and derivatized conjugates from Kigelia pinnata

Compounds which include lapachol, flavone glycosides and other chromone glycosides, atolasides I and II were isolated from the methanolic extract of the root of Kigelia pinnata. The structures of the compounds were determined based on combination of spectroscopic techniques. Lapachol, the major compound in the extract was derivatized to enhance the selectivity to cancer cells. The in vitro cytotoxic activities of the compounds were evaluated on cell lines using MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] colorimetric assay. Healthy human prostate (PC-3) and human cervical cancer (Hela) and mouse fibroblast (3T3) cells (obtained from the American Type Culture Collection, ATCC) were maintained and treated with various concentrations (1 – 100µM) of compounds to establish their potentials to inhibit cell proliferation. Lapachol, a naphthoquinone, was most cytotoxic to prostate (IC₅₀= 20.51 µg/mL), Hela cancer cell lines (IC₅₀= 19.04 µg/mL) and normal cell lines (IC₅₀= 6.15 µg/mL). However, the derivatives did not produce an increased activity against the prostate cancer cells thereby indicating the loss of activity due to release of phenolic proton. However, virtual screen indicated that the semi-synthetic derivatives are potential drug candidates. Lapachol appears to be the major contributor to the anticancer potential of the root extracts.