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Publication Type : Journal Article
Publisher : ChemMedChem
Source : ChemMedChem, Volume 15, Issue 17, p.1629-1633 (2020)
Campus : Kochi
School : School of Pharmacy
Department : Pharmaceutical Chemistry & Analysis
Year : 2020
Abstract : The general blueprint for the design of monoamine oxidase-B (MAO-B) inhibitors has been based on two phenyl or heteronuclei linked via a spacer of appropriate length. In this study, 1-[4-(morpholin-4-yl)phenyl]-5-phenylpenta-2,4-dien-1-one (MO10) was prepared by the condensation of 4'-morpholinoacetophenone and cinnamaldehyde in basic alcoholic medium. MO10 was assessed for inhibitory activity against two human MAO isoforms, MAO-A and MAO-B. Interestingly, MO10 showed a remarkable inhibition against MAO-B with an IC value of 0.044 μM along with a selectivity index of 366.13. The IC value was better than that of lazabemide (IC value of 0.063 μM), which was used as a reference. Kinetics studies revealed that MO10 acted as a competitive inhibitor of MAO-B, with a K value of 0.0080 μM. The observation of recovery of MAO-B inhibition, compared to reference levels showed MO10 to be a reversible inhibitor. MTT assays showed that MO10 was nontoxic to normal VERO cells with an IC value of 195.44 μg/mL. SwissADME predicted that MO10 provided advantageous pharmacokinetics profiles for developing agents acting on the central nervous system, that is, high passive human gastrointestinal absorption and blood-brain barrier permeability. Molecular docking simulations showed that MO10 properly entered the aromatic cage formed by Y435, Y398, and FAD of the active site of MAO-B. On the basis of these results, MO10 can be considered a promising starting compound in development of agents for the treatment of various neurodegenerative disorders.
Cite this Research Publication : N. Maliyakkal, Eom, B. Hyun, Heo, J. Hyun, Almoyad, M. Ali Abdull, Parambi, D. Grace Thom, Gambacorta, N., Nicolotti, O., Beeran, A. Appadath, Kim, H., and Bijo Mathew, “A New Potent and Selective Monoamine Oxidase-B Inhibitor with Extended Conjugation in a Chalcone Framework: 1-[4-(Morpholin-4-yl)phenyl]-5-phenylpenta-2,4-dien-1-one.”, ChemMedChem, vol. 15, no. 17, pp. 1629-1633, 2020.