Benzimidazole-based dual dipeptidyl peptidase-4 and xanthine oxidase inhibitors
Нема приказа
Аутори
Tomović, KatarinaIlić, Budimir S.
Smelcerović, Zaklina
Miljković, Marija
Yancheva, Denitsa
Kojić, Milan
Mavrova, Anelia Ts
Kocić, Gordana
Smelcerović, Andrija
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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.
Кључне речи:
Xanthine oxidase / Molecular dynamics / Dual inhibition / Dipeptidyl peptidase-4 / Cytotoxicity / BenzimidazoleИзвор:
Chemico-Biological Interactions, 2020, 315Издавач:
- Elsevier Ireland Ltd, Clare
Финансирање / пројекти:
- Faculty of Medicine of the University of Nis [4]
- L'Oreal Foundation
- Добијање, физичко-хемијска карактеризација, аналитика и биолошка активност фармаколошки активних супстанци (RS-MESTD-Basic Research (BR or ON)-172044)
- Електрични пробој гасова, површински процеси и примене (RS-MESTD-Basic Research (BR or ON)-171025)
- Изучавање гена и молекуларних механизама у основи пробиотичке активности бактерија млечне киселине изолованих са подручја западног Балкана (RS-MESTD-Basic Research (BR or ON)-173019)
- Производња нових дијететских млечних производа за ризичне популације заснована на квалитативној и квантитативној анализи биохемијских маркера здравственог ризика конзумирања млека (RS-MESTD-Technological Development (TD or TR)-31060)
Напомена:
- Peer-reviewed version: https://intor.torlakinstitut.com/handle/123456789/699
Повезане информације:
- Друга верзија
https://intor.torlakinstitut.com/handle/123456789/699
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
Институција/група
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 . .