Design Synthesis and Evaluation of Lantadene Derivatives as Potential Anticancer Agents

Abstract

Phytochemicals encompass a diverse chemical space for drug discovery. Pentacyclic triterpenoids are emerging as an important drug leads for various diseases. Some of the metabolites like lantadenes from the weed Lantana camara have been known to inhibit cell division and showed anti-antitumor potential. Herein, present work cantered on isolation of the lantadenes from the weed lantana; QSAR inspired designing and synthesis of novel lantadenes; in vitro; in silico and in vivo anticancer studies. Different 3and#946; substituted esters (ND 1-6) and ethers (ND 7-12) of 22and#946;-angeloyloxy-olean-12-en-28-oic acid and 22and#946;-senecioyloxy-olean-12-en-28-oic acid have been synthesized. Lantadene A and B, reduced lantadenes and all the newly synthesized lantadene esters ND 1-6 and ethers analogs ND 7-12 were evaluated for their cytotoxicity profile against the A375, A431 cancer cell lines. Outcomes rendered us 3and#946;-(4-Methoxybenzoyloxy)-22and#946;-senecioyloxy-olean-12-en-28-oic acid (ND-6) as a lead molecule. The cytotoxicitiy studies were also found in aggrement with molecular binding studies. ND-6 was taken forward to explore its potential against skin cancer using two stage carcinoma model, and assessed for parameters like body weight, incidence of papillomas, number of tumors, survived animals, tumor volume and tumor burden. ND-6 showed significant reduction in tumor incidence, tumor volume and tumor burden in comparison to the DMBA/TPA treated animals. Histopathological analysis, showed attenuation in hyperprolition, keratin pearls and corrugated epidermis with areas of empty spaces (degenerative changes) in comparison to DMBA/TPA group. This current study based upon computational technologies along with in vitro, in vivo studies provided ND-6 as a promising anticancer molecule. newline