Evaluation in silico and ex vivo: Determining affinity, selectivity and presumable allosteric modulation of new compounds towards β1/β2 adrenoceptors

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

November 02-04, 2015 Atlanta, USA

Jos�© Ra�ºl Bahena Herrera, Erik Andrade Jorge, Jesus Garc�­a G�¡mez, Marvin Soriano Ursua and Jos�© G Trujillo Ferrara

Instituto Polit�©cnico Nacional, M�©xico

Posters-Accepted Abstracts: Med chem

Abstract :

Adrenergic receptors are important targets for pharmaceutical development and physiological studies. Although several drugs have been designed as agonist/antagonist for these receptors, the insights for rational design of highly selective molecules are still not widely described nor used. Therefore the aim for the present study was to determine the affinity and selectivity of a series of new rationally designed isoindoline derivatives with �²1/�²2 adrenoceptors. We performed a global and local reactivity evaluation of the best ligands with �²2 adrenoceptor in order to understand the selectivity of the binding pocket. The results of the in silico experiments suggest that our molecules might be metabolized by CYP450 and they are in agreement with the Lipinskiâ��s rule of five; the docking studies show that the ligands interact with the orthosteric site of �²2-adrenoceptors and with the orthosteric and allosteric site of �²1 adrenoceptor with more selectivity for the first one. The ex vivo results in the isolated guinea pig trachea model indicates that EC50 for the molecule MD2p13-16 was 2.39 x 10-8 M, with a ��G of -10.8�±1.2 Kcal/Mol. Finally Molecule MD2p13-16 have a higher potency in comparison to albuterol for concentrations 1 x10-10, 1 x 10-9.5, 1 x10-9 and 1 x10-8.5 M; all the above information allows us to propose that the designed drug works as a partial agonist of �²2-adrenoceptor and according to Hillâ��s equation we can associate a phenomenon of negative cooperativity.

Biography :

Email: joseraul_bahena@hotmail.com