Naslov
Progressive inhibition of human dipeptidyl peptidase iii by new amidino-substituted-benzimidazoles

Autori
Agić, Dejan ; Hranjec, Marijana ; Jajčanin, Nina ; Starčević, Kristina ; Vukelić, Bojana ; Karminski-Zamola, Grace ; Abramić, Marija

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

Izvornik
Kongres hrvatskog društva za biokemiju i molekularnu biologiju prigodom 30. obljetnice osnutka uz međunarodno sudjelovanje (HDBMB 2006) : knjiga sažetaka = Congress of the Croatian Society of Biochemistry and Molecular Biology on the occasion of the 30th Anniversary with international participation : book of abstracts / Kovarik, Zrinka - Zagreb : Hrvatsko društvo za biokemiju i molekularnu biologiju (HDBMB), 2006, 83-83

ISBN
953-95551-0-8

Skup
Kongres hrvatskog društva za biokemiju i molekularnu biologiju prigodom 30. obljetnice osnutka uz međunarodno sudjelovanje

Mjesto i datum
Vodice, Hrvatska, 03.10.2006. - 07.10.2006

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
Amidino-substituted benzimidazoles; Dipeptidyl peptidase III inhibitors

Sažetak
Dipeptidyl peptidase III (DPP III), also known as enkephalinase B, is a zinc-hydrolase for which the role in mammalian pain modulatory system is indicated. In search of new and more potent inhibitors of human DPP III, we have synthesized and screened the effect of 14 benzimidazole derivatives on its activity. Among them, two compounds (1' and 4') obtained by photochemical cyclization in water respecting the « green chemistry» approach were found to be strong inhibitors, with IC50 value below 5 μ M, both in the group of cyclobutane derivatives containing the amidino-substituted benzimidazole moieties. The inhibition with compound 1' was studied in more detail and it was shown that its mode of action is not via nonspecific chelation. Compound 1' displayed time-dependent inhibition towards human DPP III, characterized by the second-order rate constant of 6924± 549 M-1 min-1 (Ki = 0.20 μ M). Peptide substrate protected the enzyme from inactivation by 1'. This investigation yielded new non-peptidic inhibitors of human proteolytic enzyme DPP III, whose structural features important for strong inhibitory activity are amidino group (preferably cyclized) coupled to benzimidazole moiety and an additional aromatic ring which presumably interacts with DPP III hydrophobic pocket S1'.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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