title: Synthesis, QSAR, and Molecular Dynamics Simulation of Amidino-substituted Benzimidazoles as Dipeptidyl Peptidase III Inhibitors.
abstract: A molecular modeling study is performed on series of benzimidazol-based inhibitors of human dipeptidyl peptidase III (DPP III). An eight novel compounds were synthesized in excellent yields using green chemistry approach. This study is aimed to elucidate the structural features of benzimidazole derivatives required for antagonism of human DPP III activity using Quantitative Structure-Activity Relationship (QSAR) analysis, and to understand the mechanism of one of the most potent inhibitor binding into the active site of this enzyme, by molecular dynamics (MD) simulations. The best model obtained includes S3K and RDF045m descriptors which have explained 89.4 % of inhibitory activity. Depicted moiety for strong inhibition activity matches to the structure of most potent compound. MD simulation has revealed importance of imidazolinyl and phenyl groups in the mechanism of binding into the active site of human DPP III.
authors.forename: Vesna
authors.initials: V
authors.lastname: Rastija
authors.forename: Dejan
authors.initials: D
authors.lastname: Agić
authors.forename: Sanja
authors.initials: S
authors.lastname: Tomiš
authors.forename: Sonja
authors.initials: S
authors.lastname: Nikolič
authors.forename: Marijana
authors.initials: M
authors.lastname: Hranjec
authors.forename: Karminski-Zamola
authors.initials: KZ
authors.lastname: Grace
authors.forename: Marija
authors.initials: M
authors.lastname: Abramić
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors*; D006801:Humans; D056004:Molecular Dynamics Simulation; D021281:Quantitative Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C100152:dipeptidyl peptidase III