Benzimidazole-based dual dipeptidyl peptidase-4 and xanthine oxidase inhibitors
Autori
Tomović, KatarinaIlić, Budimir S.
Smelcerović, Zaklina
Miljković, Marija
Yancheva, Denitsa
Kojić, Milan
Mavrova, Anelia Ts
Kocić, Gordana
Smelcerović, Andrija
Članak u časopisu (Recenzirana verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Multiple-targeting compounds might reduce complex polypharmacy of multifactorial diseases, such as diabetes, and contribute to the greater therapeutic success. Targeting reactive oxygen species-producing enzymes, as xanthine oxidase (XO), might suppress progression of diabetes-associated vascular complications. In this study a small series of benzimidazole derivatives (1-9) was evaluated for inhibitory activity against dipeptidyl peptidase-4 (DPP-4) and XO. One 1,3-disubstituted-benzimidazole-2-imine (5) and 1,3-thiazolo [3,2-a] benzimidazolone derivative (8) were shown as effective dual DPP-4 and XO inhibitors, with IC50 values lower than 200 mu M, and predicted binding modes with both target enzymes. Both selected dual inhibitors (compounds 5 and 8) did not show cytotoxicity to a greater extent on Caco-2 cells even at concentration of 250 mu M. These structures represent new non-purine scaffolds bearing two therapeutic functionalities, being DPP-4 and XO inhibitors, more favorable in... comparison to DPP-4 inhibitors with DPP-4 as a single target due to pleiotropic effects of XO inhibition.
Ključne reči:
Xanthine oxidase / Molecular dynamics / Dual inhibition / Dipeptidyl peptidase-4 / Cytotoxicity / BenzimidazoleIzvor:
Chemico-Biological Interactions, 2020, 315Izdavač:
- Elsevier Ireland Ltd, Clare
Finansiranje / projekti:
- Faculty of Medicine of the University of Nis [4]
- L'Oreal Foundation
- Dobijanje, fizičko-hemijska karakterizacija, analitika i biološka aktivnost farmakološki aktivnih supstanci (RS-MESTD-Basic Research (BR or ON)-172044)
- Električni proboj gasova, površinski procesi i primene (RS-MESTD-Basic Research (BR or ON)-171025)
- Izučavanje gena i molekularnih mehanizama u osnovi probiotičke aktivnosti bakterija mlečne kiseline izolovanih sa područja zapadnog Balkana (RS-MESTD-Basic Research (BR or ON)-173019)
- Proizvodnja novih dijetetskih mlečnih proizvoda za rizične populacije zasnovana na kvalitativnoj i kvantitativnoj analizi biohemijskih markera zdravstvenog rizika konzumiranja mleka (RS-MESTD-Technological Development (TD or TR)-31060)
Napomena:
- This is the peer-reviewed version of the article: Tomović, K.; Ilić, B. S.; Smelcerović, Z.; Miljković, M.; Yancheva, D.; Kojić, M.; Mavrova, A. T.; Kocić, G.; Smelcerović, A. Benzimidazole-Based Dual Dipeptidyl Peptidase-4 and Xanthine Oxidase Inhibitors. Chemico-Biological Interactions 2020, 315. https://doi.org/10.1016/j.cbi.2019.108873.
Povezane informacije:
- Druga verzija
https://doi.org/10.1016/j.cbi.2019.108873 - Druga verzija
https://intor.torlakinstitut.com/handle/123456789/698
DOI: 10.1016/j.cbi.2019.108873
ISSN: 0009-2797
PubMed: 31669219
WoS: 000514572800013
Scopus: 2-s2.0-85074070795
URI
https://imagine.imgge.bg.ac.rs/handle/123456789/1376http://intor.torlakinstitut.com/handle/123456789/699
Institucija/grupa
TorlakTY - JOUR AU - Tomović, Katarina AU - Ilić, Budimir S. AU - Smelcerović, Zaklina AU - Miljković, Marija AU - Yancheva, Denitsa AU - Kojić, Milan AU - Mavrova, Anelia Ts AU - Kocić, Gordana AU - Smelcerović, Andrija PY - 2020 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1376 UR - http://intor.torlakinstitut.com/handle/123456789/699 AB - Multiple-targeting compounds might reduce complex polypharmacy of multifactorial diseases, such as diabetes, and contribute to the greater therapeutic success. Targeting reactive oxygen species-producing enzymes, as xanthine oxidase (XO), might suppress progression of diabetes-associated vascular complications. In this study a small series of benzimidazole derivatives (1-9) was evaluated for inhibitory activity against dipeptidyl peptidase-4 (DPP-4) and XO. One 1,3-disubstituted-benzimidazole-2-imine (5) and 1,3-thiazolo [3,2-a] benzimidazolone derivative (8) were shown as effective dual DPP-4 and XO inhibitors, with IC50 values lower than 200 mu M, and predicted binding modes with both target enzymes. Both selected dual inhibitors (compounds 5 and 8) did not show cytotoxicity to a greater extent on Caco-2 cells even at concentration of 250 mu M. These structures represent new non-purine scaffolds bearing two therapeutic functionalities, being DPP-4 and XO inhibitors, more favorable in comparison to DPP-4 inhibitors with DPP-4 as a single target due to pleiotropic effects of XO inhibition. PB - Elsevier Ireland Ltd, Clare T2 - Chemico-Biological Interactions T1 - Benzimidazole-based dual dipeptidyl peptidase-4 and xanthine oxidase inhibitors VL - 315 DO - 10.1016/j.cbi.2019.108873 ER -
@article{ author = "Tomović, Katarina and Ilić, Budimir S. and Smelcerović, Zaklina and Miljković, Marija and Yancheva, Denitsa and Kojić, Milan and Mavrova, Anelia Ts and Kocić, Gordana and Smelcerović, Andrija", year = "2020", abstract = "Multiple-targeting compounds might reduce complex polypharmacy of multifactorial diseases, such as diabetes, and contribute to the greater therapeutic success. Targeting reactive oxygen species-producing enzymes, as xanthine oxidase (XO), might suppress progression of diabetes-associated vascular complications. In this study a small series of benzimidazole derivatives (1-9) was evaluated for inhibitory activity against dipeptidyl peptidase-4 (DPP-4) and XO. One 1,3-disubstituted-benzimidazole-2-imine (5) and 1,3-thiazolo [3,2-a] benzimidazolone derivative (8) were shown as effective dual DPP-4 and XO inhibitors, with IC50 values lower than 200 mu M, and predicted binding modes with both target enzymes. Both selected dual inhibitors (compounds 5 and 8) did not show cytotoxicity to a greater extent on Caco-2 cells even at concentration of 250 mu M. These structures represent new non-purine scaffolds bearing two therapeutic functionalities, being DPP-4 and XO inhibitors, more favorable in comparison to DPP-4 inhibitors with DPP-4 as a single target due to pleiotropic effects of XO inhibition.", publisher = "Elsevier Ireland Ltd, Clare", journal = "Chemico-Biological Interactions", title = "Benzimidazole-based dual dipeptidyl peptidase-4 and xanthine oxidase inhibitors", volume = "315", doi = "10.1016/j.cbi.2019.108873" }
Tomović, K., Ilić, B. S., Smelcerović, Z., Miljković, M., Yancheva, D., Kojić, M., Mavrova, A. T., Kocić, G.,& Smelcerović, A.. (2020). Benzimidazole-based dual dipeptidyl peptidase-4 and xanthine oxidase inhibitors. in Chemico-Biological Interactions Elsevier Ireland Ltd, Clare., 315. https://doi.org/10.1016/j.cbi.2019.108873
Tomović K, Ilić BS, Smelcerović Z, Miljković M, Yancheva D, Kojić M, Mavrova AT, Kocić G, Smelcerović A. Benzimidazole-based dual dipeptidyl peptidase-4 and xanthine oxidase inhibitors. in Chemico-Biological Interactions. 2020;315. doi:10.1016/j.cbi.2019.108873 .
Tomović, Katarina, Ilić, Budimir S., Smelcerović, Zaklina, Miljković, Marija, Yancheva, Denitsa, Kojić, Milan, Mavrova, Anelia Ts, Kocić, Gordana, Smelcerović, Andrija, "Benzimidazole-based dual dipeptidyl peptidase-4 and xanthine oxidase inhibitors" in Chemico-Biological Interactions, 315 (2020), https://doi.org/10.1016/j.cbi.2019.108873 . .