Naslov
2D i 3D molekulsko modeliranje derivata benzimidazola kao inhibitora dipeptidil- peptidaze III
(2D and 3D molecular modelling of benzimidazole derivatives as dipeptidyl peptidase III inhibitors)

Autori
Rastija, Vesna ; Agić, Dejan ; Tomić, Sanja ; Nikolić ; Sonja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
XV. Ružičkini dani “Danas znanost – sutra industrija” 11. i 12. rujna 2014. Vukovar, Hrvatska knjiga sažetaka / Drago Šubarić - Osijek : Prehrambeno tehnološki fakultet Sveučilišta Josipa Jurja Strossmayera u Osijeku, 2014, 109-109

Skup
International Scientific and Professional Conference 15th Ružička days “Today science – tommorow industry”

Mjesto i datum
Vukovar, Hrvatska, 11.09.2014. - 12.09.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
molecular modelling ; benzimidazole derivatives ; DPP III ; inhibitors

Sažetak
A molecular modelling study was performed on a series of benzimidazo-based inhibitors of human dipeptidyl peptidase III (DPP III). DPP III is a zinc-dependent aminopeptidase with indicated role in pathophysiological processes, such as: pain, ovarian carcinoma, oxidative stress, inflammation and cataractogenesis [1]. Previous research has shown that cyclobutane derivatives containing amidinosubstituted benzimidazole moieties areimportant for the inhibitory activity of human DPP III [2]. Since benzimidazole derivates have shown wide variations in their structures, this study was aimed to elucidate the structural features of benzimidazole derivatives required for antagonism of dipeptiyl peptidase III inhibitors using Quantitative Structure- Activity Relationship (QSAR) analysis. QSAR is a cheminformatic technique for establishing the quantitative relationship between biological activity and descriptors representing physicochemical properties of the compounds in a series using statistical methods. "Two- dimensional" (2D), "three-dimensional" (3D) molecular descriptors, quantum chemical descriptors, and physicochemical parameters, derived from optimised threedimensional structure, have been calculated usingthe Dragon program and HyperChem 8.0. Multiple regression analysis was performed using STATISTICA 7.0. Selection of predictor variables for multiple regression was performed by best-subset method. QSAR is aimed to elucidate the structural features of benzimidazole derivatives required for antagonism of dipeptidyl peptidase III inhibitors. In order to understand the mechanism of the most potent inhibitor binding into the active site of human DPP III we performed docking by AutoDock4 program and molecular dynamicsimulation with the AMBER10 package. The presented study can guide the rational synthesis of novel inhibitors with increased affinity and efficacy.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

Napomena
Rad je napisan u sklopu projekta Sveučilišta J.J. Strossmayera u Osijeku, 2013-2014, pod naslovom: Molekulsko modeliranje inhibicije dipeptidil- peptidaze III benzimidazolima

POVEZANOST RADA