Naslov
Interactions of human dipeptidyl petidase III with coumarinyl Schiff bases

Autori
Agić, Dejan ; Šubarić, Domagoj ; Karnaš, Maja ; Komar, Mario ; Karačić, Zrinka ; Tomić, Sanja ; Bešlo, Drago ; Rastija, Vesna ; Molnar, Maja

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

Izvornik
27th Croatian Meeting of Chemists and Chemical Engineers and 5th Symposium Vladimir Prelog : Book of Abstracts / Marković, Dean ; Meštrović, Ernest ; Namjesnik, Danijel ; Tomašić, Vesna - Zagreb : Hrvatsko kemijsko društvo, 2021, 157-157

Skup
27. hrvatski skup kemičara i kemijskih inženjera (27HSKIKI) ; 5. simpozij Vladimir Prelog

Mjesto i datum
Veli Lošinj, Hrvatska, 05.10.2021. - 08.10.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
dipeptidyl peptidase III ; coumarinyl Schiff bases ; inhibitor ; molecular docking

Sažetak
Human dipeptidyl peptidase III (hDPP III) is a zinc‐hydrolase that cleaves dipeptides sequentially from the N‐ terminal of different bioactive peptides. Although the physiological role of hDPP III is not yet fully elucidated, its involvement in pathophysiological processes such as mammalian pain modulation and blood pressure regulation emphasizes the need to find new hDPP III inhibitors. Coumarins exhibit a variety of biological activities, and Schiff bases bearing coumarin moiety in conjunction with the imino group (-C=N-) form significant compounds in medicinal and pharmaceutical chemistry. To find new potential inhibitors of hDPP III, in this research we selected 6 coumarinyl Schiff bases to investigate their interactions with hDPP III, combining experimental and computational approaches. hDPP III activity was determined using the spectrophotometric assay, while molecular docking was performed by AutoDock Vina software to obtain information regarding the possible interactions of the strongest inhibitor and hDPP III binding site. The experimental results showed that all analyzed compounds have an inhibitory effect against hDPP III activity at the physiological concentration i.e., 100 μM. The strongest inhibition (87.9 %) has been obtained with compound 5. Docking predicts that 5 interacts with amino acid residues of hDPP III mostly in the region of inter-domain cleft by forming hydrogen bonds with Ile386, His568 and Arg572, π – interactions with Phe109, Pro387 and Ala388, and numerous van der Waals interactions. Most of these residues are found to be constituents of the hDPP III substrate binding subsites S1, S1’, S2, S2’ and S3’. The results of this study provide an insight into the coumarinyl Schiff bases inhibitory activity and interactions toward hDPP III.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Interdisciplinarne prirodne znanosti

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