Development of a Novel Class of Pyridazinone Derivatives as Selective MAO-B Inhibitors

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dc.authoridalagoz, mehmet abdullah/0000-0001-5190-7196
dc.authoridGambacorta, Nicola/0000-0003-1965-1519
dc.authoridNaguib, Ibrahim A/0000-0002-5923-1466
dc.authoridGhoneim, Mohammed M./0000-0002-9179-4373
dc.authoridOzdemir, Zenyep/0000-0003-4559-2305
dc.authoridabdelgawad, mohamed/0000-0001-9035-5638
dc.authoridZenni, Yaren Nur/0000-0003-0523-3826
dc.authorwosidalagoz, mehmet abdullah/W-7847-2018
dc.authorwosidGambacorta, Nicola/ACW-4658-2022
dc.authorwosidNaguib, Ibrahim A/ABM-0813-2022
dc.authorwosidZenni, Yaren Nur/AGN-0459-2022
dc.authorwosidAbdelgawad, Mohamed A./X-5943-2019
dc.authorwosidGhoneim, Mohammed M./ABE-7965-2021
dc.authorwosidOzdemir, Zenyep/AAJ-6384-2020
dc.contributor.authorAlagoz, Mehmet Abdullah
dc.contributor.authorOh, Jong Min
dc.contributor.authorZenni, Yaren Nur
dc.contributor.authorOzdemir, Zeynep
dc.contributor.authorAbdelgawad, Mohamed A.
dc.contributor.authorNaguib, Ibrahim A.
dc.contributor.authorGhoneim, Mohammed M.
dc.date.accessioned2024-08-04T20:52:04Z
dc.date.available2024-08-04T20:52:04Z
dc.date.issued2022
dc.departmentİnönü Üniversitesien_US
dc.description.abstractSixteen compounds (TR1-TR16) were synthesized and evaluated for their inhibitory activities against monoamine oxidase A and B (MAOs). Most of the derivatives showed potent and highly selective MAO-B inhibition. Compound TR16 was the most potent inhibitor against MAO-B with an IC50 value of 0.17 mu M, followed by TR2 (IC50 = 0.27 mu M). TR2 and TR16 selectivity index (SI) values for MAO-B versus MAO-A were 84.96 and higher than 235.29, respectively. Compared to the basic structures, the para-chloro substituent in TR2 and TR16 increased the inhibitory activity of MAO-B. TR2 and TR16 were reversible MAO-B inhibitors that were competitive, with K-i values of 0.230 +/- 0.004 and 0.149 +/- 0.016 mu M, respectively. The PAMPA method indicated that compounds TR2 and TR16 had the tendency to traverse the blood-brain barrier. Docking investigations revealed that lead compounds were beneficial for MAO-B inhibition via association with key as well as selective E84 or Y326 residues, but not for MAO-A inhibition via interaction primarily driven by hydrophobic contacts. In conclusion, TR2 and TR16 are therapeutic prospects for the management of multiple neurodegenerative diseases.en_US
dc.description.sponsorshipTaif University, Taif, Saudi Arabia [TURSP-2020/56]; AlMaarefa University, Riyadh, Saudi Arabia [2021-6]en_US
dc.description.sponsorshipThe authors would like to extend their sincere appreciation to Taif University Researchers Supporting Project number (TURSP-2020/56), Taif University, Taif, Saudi Arabia. Additionally, the authors deeply acknowledge the Researchers Supporting Program (TUMA-Project-2021-6), AlMaarefa University, Riyadh, Saudi Arabia.en_US
dc.identifier.doi10.3390/molecules27123801
dc.identifier.issn1420-3049
dc.identifier.issue12en_US
dc.identifier.pmid35744926en_US
dc.identifier.scopus2-s2.0-85132408012en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.3390/molecules27123801
dc.identifier.urihttps://hdl.handle.net/11616/100729
dc.identifier.volume27en_US
dc.identifier.wosWOS:000818373600001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherMdpien_US
dc.relation.ispartofMoleculesen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectpyridazinonesen_US
dc.subjectmonoamine oxidase-Ben_US
dc.subjectkineticsen_US
dc.subjectreversibilityen_US
dc.subjectPAMPAen_US
dc.subjectdockingen_US
dc.titleDevelopment of a Novel Class of Pyridazinone Derivatives as Selective MAO-B Inhibitorsen_US
dc.typeArticleen_US

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