Low cytotoxic quinoline-4-carboxylic acids derived from vanillin precursors as potential human dihydroorotate dehydrogenase inhibitors
Samo za registrovane korisnike
2021
Autori
Petrović, Milena M.Roschger, Cornelia
Chaudary, Sidrah
Zierer, Andreas
Mladenović, Milan
Marković, Violeta
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Trifunović, Snežana S.
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Joksović, Milan D.
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Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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.
Ključne reči:
DHODH inhibitors / Dihydroorotate dehydrogenase / Lipophilicity / Molecular docking / Quinoline-4-carboxylic acidsIzvor:
Bioorganic & Medicinal Chemistry Letters, 2021, 46Izdavač:
- Elsevier
Finansiranje / projekti:
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200122 (Univerzitet u Kragujevcu, Prirodno-matematički fakultet) (RS-MESTD-inst-2020-200122)
Napomena:
- Supplementary material: https://cherry.chem.bg.ac.rs/handle/123456789/4551
Povezane informacije:
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
Kolekcije
Institucija/grupa
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 . .