Benzimidazole-based dual dipeptidyl peptidase-4 and xanthine oxidase inhibitors
No Thumbnail
Authors
Tomović, KatarinaIlić, Budimir S.
Smelcerović, Zaklina
Miljković, Marija
Yancheva, Denitsa
Kojić, Milan
Mavrova, Anelia Ts
Kocić, Gordana
Smelcerović, Andrija
Article (Published version)
Metadata
Show full item recordAbstract
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.
Keywords:
Xanthine oxidase / Molecular dynamics / Dual inhibition / Dipeptidyl peptidase-4 / Cytotoxicity / BenzimidazoleSource:
Chemico-Biological Interactions, 2020, 315Publisher:
- Elsevier Ireland Ltd, Clare
Funding / projects:
- Faculty of Medicine of the University of Nis [4]
- L'Oreal Foundation
- Obtaining, physicochemical characterization, analysis and biological activity of pharmacologically active compounds (RS-MESTD-Basic Research (BR or ON)-172044)
- The electrical breakdown of gases, surface processes and applications (RS-MESTD-Basic Research (BR or ON)-171025)
- Genes and molecular mechanisms promoting probiotic activity of lactic acid bacteria from Western Balkan (RS-MESTD-Basic Research (BR or ON)-173019)
- Production of new dietetic milk products for risk populations based on qualitative and quantitative analysis of health risk markers in milk consumption (RS-MESTD-Technological Development (TD or TR)-31060)
Note:
- Peer-reviewed version: https://intor.torlakinstitut.com/handle/123456789/699
Related info:
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/123456789/698
Collections
Institution/Community
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/123456789/698 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 . .