Synthesis and cytotoxic activity of novel A-ring cleaved ursolic acid derivatives in human non-small cell lung cancer cells.

ABSTRACT: Ursolic acid (UA) is a pentacyclic triterpenoid with recognized anticancer properties. We prepared a series of new A-ring cleaved UA derivatives and evaluated their antiproliferative activity in non-small cell lung cancer (NSCLC) cell lines using 2D and 3D culture models. Compound 17, bearing a cleaved A-ring with a secondary amide at C3, was found to be the most active compound, with potency in 2D systems. Importantly, even in 3D systems, the effect was maintained albeit a slight increase in the IC50. The molecular mechanism underlying the anticancer activity was further investigated. Compound 17 induced apoptosis via activation of caspase-8 and caspase-7 and via decrease of Bcl-2. Moreover, induction of autophagy was also detected with increased levels of Beclin-1 and LC3A/B-II and decre

SUBMITTER: Mendes VIS 

PROVIDER: S-EPMC5652311 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature