22° SEMINARIO QUÍMICA ORGÁNICA IQUIR 2022

SEMINARIO QUÍMICA ORGÁNICA 03-10-22

EXPOSITOR: Lic. Elida Thobokholt

TÍTULO: "Design, synthesis, anticancer evaluation and molecular docking study of novel 2,4-dichlorophenoxymethyl-based derivatives linked to nitrogenous heterocyclic ring systems as potential CDK-2 inhibitors".

FUENTE: A .A . El-Sayed, E.S. Nossier, A .A . Almehizia et al. Journal of Molecular Structure 1247 (2022) 131285.

DÍA, HORA y LUGAR: Lunes 3 de octubre de 2022, 15:00 h, Aula 16 FBIOYF. 

Modalidad virtual, Link: meet.google.com/hjn-ygro-twf (Plataforma MEET GOOGLE)

RESUMEN: A novel series of 2,4-dichlorophenoxymethyl-based derivatives 4 - 18 bearing various nitrogenous hetero- cyclic systems have been designed and synthesized through molecular hybridization approach. The anti- proliferative activity of all newly synthesized derivatives was established against human HCT-116 and MCF-7 cancer cell lines. The structure–activity relationship (SAR) studies exhibited that the derivatives in- corporated with pyrido[3,2- d ]pyrimidine, naphtho[2,3- e ][1,3]oxazine-5-sulfonic acid, benzo[ d ]thiazole and benzo[ d ]oxazole scaffolds revealed the highest cytotoxic activities comparing with doxorubicin as a refer- ence drug. The promising derivatives 5, 9, 13 and 15 were subjected to enzymatic inhibitory assessment against CDK-2/cyclin A2 using roscovitine as a standard. Concerning their effects upon the apoptotic pro- cess, they upregulated Bax, p-53 and caspase-3 levels and downregulated Bcl-2, causing induction of apoptosis. Moreover, the in silico molecular docking was applied to investigate the possible binding modes and orientations within the active site of CDK-2.