Synthesis of 3-aryl-4-(N-aryl)aminocoumarins via photoredox arylation and the evaluation of their biological activity

dc.creatorCarneiro, Leonardo S. A.
dc.creatorSouza, Fernando Almeida
dc.creatorLopes, Yanne S. C.
dc.creatorNovas, Rachel C.V.
dc.creatorSantos, Kaique Bertrand Almeida
dc.creatorLigiero, Carolina B. P.
dc.creatorCalabrese, Kátia da Silva
dc.creatorBuarque, Camilla D.
dc.date2021-07-19T17:06:09Z
dc.date2021-07-19T17:06:09Z
dc.date2021
dc.date.accessioned2023-09-26T20:33:52Z
dc.date.available2023-09-26T20:33:52Z
dc.identifierCARNEIRO, Leonardo S. A. et al. Synthesis of 3-aryl-4-(N-aryl)aminocoumarins via photoredox arylation and the evaluation of their biological activity. Journal Pre-proofs, p. 1-45, 2021.
dc.identifierElsevier Inc.
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/48281
dc.identifier10.1016/j.bioorg.2021.105141
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8859613
dc.descriptionA new series of 3-aryl-4-(N-aryl)aminocoumarins was synthesized in two steps starting from the natural product 4-hydroxycoumarin using the photoredox catalysis for the key step. These conditions reactions allowed to make C-C bonds is up to 95% yields in mild conditions, easy operation, in an environmentally benign way, and are compatible with several patterns of substitution. The biological activity of the new compounds was tested in vitro against MCF-7, MDA-MB-231, and CCD-1072Sk cancer cell lines, as soon as to promastigotes and intracellular amastigotes of Leishmania amazonensis. Compounds 17d, 17s and 17x showed activity against promastigote forms (IC50 = 5.96 ± 3.210, 9.05 ± 2.855 and 5.65 ± 2.078 μM respectively), and compound 17x presented the best activity against L. amazonensis amastigote intracellular form (IC50 = 9.6 ± 1.148 μM), no BALB/c peritoneal macrophage cytotoxicity at assayed concentrations (CC50 > 600 μM), and high selectivity to parasites over the mammalian cells (Selectivity Index > 62.2). There was no expressive activity for the cancer cell lines. Single crystal X-ray diffraction analysis was employed for structural elucidation of compounds 17a and 17s. In silico analyses of physicochemical, pharmacokinetic, and toxicological properties suggest that compound 17x is a potential candidate for anti-leishmaniasis drugs.
dc.description2023
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.rightsrestricted access
dc.subjectDifração de Raios X
dc.subjectLeishmaniose
dc.subjectCitotoxidade
dc.subjectFarmacocinética
dc.subjectAminocoumarin
dc.subjectArylation
dc.subjectArylcoumarin
dc.subjectPhotoredox catalysis
dc.subjectX-ray diffraction
dc.subjectLeishmaniasis
dc.subjectCytotoxicity
dc.subjectin silico
dc.subjectADMET
dc.subjectDifração de Raios X
dc.subjectCitotoxicidade Celular Dependente de Anticorpos
dc.subjectModelos Computacionais
dc.subjectFarmacocinética
dc.titleSynthesis of 3-aryl-4-(N-aryl)aminocoumarins via photoredox arylation and the evaluation of their biological activity
dc.typePreprint


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