Design of benzimidazoles, benzoxazoles, benzothiazoles and thiazolopyridines as leukotriene A4 hydrolase inhibitors through 3D-QSAR, docking and molecular dynamics

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dc.contributor.authorLorca, Marcos
dc.contributor.authorFaundez, Mario
dc.contributor.authorPessoa-Mahana, C. David
dc.contributor.authorRecabarren-Gajardo, Gonzalo
dc.contributor.authorDiethelm-Varela, Benjamin
dc.contributor.authorMillan, Daniela
dc.contributor.authorCelik, Ismail
dc.contributor.authorMellado, Marco
dc.contributor.authorAraque, Ileana
dc.contributor.authorMella, Jaime
dc.contributor.authorRomero-Parra, Javier
dc.date.accessioned2025-01-20T20:20:00Z
dc.date.available2025-01-20T20:20:00Z
dc.date.issued2023
dc.description.abstractHuman leukotriene A4 hydrolase enzyme (LTA4H) catalyses the biotransformation of the inactive precursor leukotriene A4 (LTA4) to the bioactive Leukotriene B4 (LTB4), which causes many inflammatory responses in the human body. Therefore, the selective inhibition of this enzyme becomes a useful strategy for the treatment of several illnesses such as asthma, allergic rhinitis, cardiovascular diseases, and cancer. Herein we report a 3D-QSAR/ /CoMFA and CoMSIA study on a series of 47 benzimidazoles, benzoxazoles, benzothiazoles and thiazolopyridines reported as potent LTA4H inhibitors. Good statistical parameters were obtained for the best model (q2 = 0.568, r2 ncv = 0.891 and r2 test = 0.851). A new series of 10 compounds capable of inhibiting leukotriene A4 hydrolase with high potency was presented. All designed inhibitors showed low IC50 in nano- and sub-nanomolar ranges, when they were evaluated in 3D-QSAR models. Subsequently, the designed molecules, as well as the least and most active compounds were subjected to docking and molecular dynamics studies into LTA4H. In conclusion, we summarised a thorough structure-activity relationship (SAR) of LTA4H inhibitors of heterocyclic structure. These models can be used for the rational proposal of new inhibitors.
dc.fuente.origenWOS
dc.identifier.doi10.2298/JSC220427068L
dc.identifier.issn0352-5139
dc.identifier.urihttps://doi.org/10.2298/JSC220427068L
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/92555
dc.identifier.wosidWOS:000898839000001
dc.issue.numero1
dc.language.isoen
dc.pagina.final39
dc.pagina.inicio25
dc.revistaJournal of the serbian chemical society
dc.rightsacceso restringido
dc.subjectCoMFA
dc.subjectCoMSIA
dc.subjectbinding free energy calculation
dc.subjectCADD
dc.subjectinflamemation
dc.subjectallergy
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleDesign of benzimidazoles, benzoxazoles, benzothiazoles and thiazolopyridines as leukotriene A4 hydrolase inhibitors through 3D-QSAR, docking and molecular dynamics
dc.typeartículo
dc.volumen88
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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