Design, synthesis and evaluation of lantadene A congener with hydroxyl functionality in ring A as an antitumour agent.

Pentacyclic triterpenoid lantadene A congener with hydroxyl functionality in ring A was designed and synthesised on the basis of enhancement of polarity and bioactivity. The new synthesised compound 22β-angeloyloxy-methyl-2-hydroxy-3-oxoolean-1,12-dien-28-oate (6) was screened for cytotoxicity against human cancer cell lines (HL-60, HeLa, Colon 502713 and A-549) and showed a better cytotoxicity than the parent compound (p < 0.05). Further, compound 6 was screened for in vivo antitumour activity in a two-stage squamous cell carcinogenesis model, using female Swiss albino mice. Compound 6 showed a better tumour inhibition profile than the parent compound. Compound 6 also exhibited a marked decrease in protein expression of activator protein-1 (c-jun), nuclear factor-kappa B (p65) and p55. The results inferred that an increase in polarity of the lead molecule not only increased the antitumour activity but also reduced the dose, which may be linked to the deregulation of the abovementioned molecular targets, and warrants further optimisation of the structure to make it a drug-like candidate. [ABSTRACT FROM AUTHOR]