α-Glucosidase Inhibitory Isomeric Corniculatolides from the Stems of the Indian Mangrove Plant, Xylocarpus granatum.

Three new isomeric corniculatolides (1, 2, and 3) with an unusual caffrane and isocorniculane framework, and five known metabolites were isolated from the chloroform extract of the stems of Xylocarpus granatum. The structures of the new metabolites were deduced as corniculatolide B (1), isocorniculatolide B (2), and corniculatolide C (3) by spectroscopic data analysis and a combination of chemical transformations and supported by single-crystal X-ray crystallographic data of 1 and 3. The isolated compounds were evaluated for their in vitro cytotoxicity and α-glucosidase (Saccharomyces cerevisiae) inhibitory potential. Compound 3 possessed α-glucosidase inhibitory activity with an IC50 value of 24.8 µM, whereas these rare macrolides showed no effect on the mammalian cancer cell lines MIAPaCa-2, DU145, MCF-7, and HTC-116.

Impact of Hybrid-polar Histone Deacetylase Inhibitor m-Carboxycinnamic Acid bis-Hydroxyamide on Human Pancreatic Adenocarcinoma Cells.

BACKGROUND: Histone deacetylase inhibitors (HDACIs) have got immense importance as promising drugs for cancer treatment as these inhibitors regulate cellular differentiation, gene expression, cell cycle arrest and apoptosis. The current study investigates the effect of the hybrid-polar HDACI m-carboxycinnamic acid bishydroxyamide (CBHA) on the growth of human pancreatic adenocarcinoma cells, using the cell line MIA PaCa- 2 as an in vitro model. METHODS: Following CBHA treatment of the MIA PaCa-2 cells, we characterized the effect of CBHA by in vitro cytotoxicity evaluation, clonogenic assay, cell cycle analysis, immunoblotting for soluble and insoluble fractions of tubulin, immunofluorescence and caspase-3 assay. RESULTS: We observed that the histone deacetylase inhibitor CBHA markedly impaired growth of the pancreatic cancer cells by resulting in dose-dependent G2/M arrest, disruption of microtubule organization, induction of caspase-mediated apoptosis and in vitro suppression of HDAC6. Our study also shows that inhibition of HDAC6 by CBHA induced acetylation of α-tubulin. CONCLUSION: Together, our findings show that CBHA can be a potential plausible therapeutic that could be exploited for pancreatic cancer therapy.