Molecular docking and in vitro assay of isoindolina-1,3-dione amine derivative as novel HDAC8 inhibitor for cancer treatment

4^th International Conference on Medicinal Chemistry & Computer Aided Drug Designing

November 02-04, 2015 Atlanta, USA

Garcia Gamez Jesus, Bahena Herrera Jos�© Raul, Sixto L�³pez Yudibeth, Trujillo Ferrrara Jos�© Guadalupe and Andrade Jorge Erik

Escuela Superior de Medicina del Instituto Polit�©cnico Nacional, Mexico

Posters-Accepted Abstracts: Med chem

Abstract :

Cancer is an uncontrolled process of growth and dissemination that can appear ubiquitously. Genetic and epigenetic mutations in cancer cells elicit protection of tumor cells like overexpression of histone deacetylase (HDAC). HDAC inhibitors (HDACi) have shown that over acetylated state induce anticancer effects like apoptosis, cytostasis, differentiation and angiogenesis inhibition. HDAC8 is overexpressed in different types of cancer such as colon, breast, lung, pancreas, ovary, etc. Therefore, we modeled a serie of isoindoline-1,3-dione due to their homology with thalidomide�s metabolites and also similar to HDACi previously reported just as sodium butirate, sodium valproate, phenylbutanoic acid, etc. Docking results showed our ligand DxD2-15 interacting with HDAC8 in the catalytic site with the amino acid residues Phe208, Phe152, His180, Met214, Asp178, Tyr306, Gly303 and Gly304 suggesting possible inhibitory effect. Anti-tumoral capacity of DxD2-15 was tested in different concentrations at 24 and 48 h on L5178-Y murine leukemia cells with MTT assay. Cellular viability decreased importantly after 24 and 48 h of culture. There was a significant decrease in cell viability caused by DxD2-15 at all times and concentrations of 1X10-4 M, 1X10-5 M and 1X10-6 M showing DxD2-15 as a potent anti-tumoral drug compared with control cells (P<0.05). With these important results we propose to perform more experiments on other cell lines such as HeLa, Vero and prostate cancer cells and also perform in vivo experiments in male Balb/C mice.

Biography :

Garcia Gamez Jesus is a medical student of Escuela Superior de Medicina at Instituto Politécnico Nacional. He is a junior researcher who has been working at Biochemistry Department since 2013 on different research lines such as asthma, Parkinson’s and obesity. His recent research is focused on drug design for cancer treatment.

Email: jjcgg2330@hotmail.com