Low cytotoxic quinoline-4-carboxylic acids derived from vanillin precursors as potential human dihydroorotate dehydrogenase inhibitors
Само за регистроване кориснике
2021
Аутори
Petrović, Milena M.Roschger, Cornelia
Chaudary, Sidrah
Zierer, Andreas
Mladenović, Milan
Marković, Violeta
Trifunović, Snežana S.
Joksović, Milan D.
Метаподаци
Приказ свих података о документуАпстракт
Twenty novel 2-substituted quinoline-4-carboxylic acids bearing amide moiety were designed and synthesized by Doebner reaction. Human dihydroorotate dehydrogenase (hDHODH) was recognized as a biological target and all compounds were screened as potential hDHODH inhibitors in an enzyme inhibition assay. The prepared heterocycles were also evaluated for their cytotoxic effects on the healthy HaCaT cell line while lipophilic properties were considered on the basis of experimentally determined logD values at physiological pH. The most promising compound 5j, with chlorine at para-position of terminal phenyl ring, showed good hDHODH inhibitory activity, low cytotoxicity, and optimal lipophilicity. The bioactive conformation of 5j on the hDHODH, determined by means of molecular docking, revealed the compound’s pharmacology and provide guidelines for further lead optimization.
Кључне речи:
DHODH inhibitors / Dihydroorotate dehydrogenase / Lipophilicity / Molecular docking / Quinoline-4-carboxylic acidsИзвор:
Bioorganic & Medicinal Chemistry Letters, 2021, 46Издавач:
- Elsevier
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200122 (Универзитет у Крагујевцу, Природно-математички факултет) (RS-MESTD-inst-2020-200122)
Напомена:
- Supplementary material: https://cherry.chem.bg.ac.rs/handle/123456789/4551
Повезане информације:
DOI: 10.1016/j.bmcl.2021.128194
ISSN: 0960-894X
WoS: 000664981400002
Scopus: 2-s2.0-85107666267
URI
https://www.sciencedirect.com/science/article/pii/S0960894X21004212https://cherry.chem.bg.ac.rs/handle/123456789/4550
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryPetrović, M. M., Roschger, C., Chaudary, S., Zierer, A., Mladenović, M., Marković, V., Trifunović, S. S.,& Joksović, M. D.. (2021). Low cytotoxic quinoline-4-carboxylic acids derived from vanillin precursors as potential human dihydroorotate dehydrogenase inhibitors. in Bioorganic & Medicinal Chemistry Letters Elsevier., 46. https://doi.org/10.1016/j.bmcl.2021.128194
Petrović MM, Roschger C, Chaudary S, Zierer A, Mladenović M, Marković V, Trifunović SS, Joksović MD. Low cytotoxic quinoline-4-carboxylic acids derived from vanillin precursors as potential human dihydroorotate dehydrogenase inhibitors. in Bioorganic & Medicinal Chemistry Letters. 2021;46. doi:10.1016/j.bmcl.2021.128194 .
Petrović, Milena M., Roschger, Cornelia, Chaudary, Sidrah, Zierer, Andreas, Mladenović, Milan, Marković, Violeta, Trifunović, Snežana S., Joksović, Milan D., "Low cytotoxic quinoline-4-carboxylic acids derived from vanillin precursors as potential human dihydroorotate dehydrogenase inhibitors" in Bioorganic & Medicinal Chemistry Letters, 46 (2021), https://doi.org/10.1016/j.bmcl.2021.128194 . .