000124419 001__ 124419
000124419 005__ 20241125101134.0
000124419 0247_ $$2doi$$a10.1016/j.arabjc.2022.104514
000124419 0248_ $$2sideral$$a132842
000124419 037__ $$aART-2023-132842
000124419 041__ $$aeng
000124419 100__ $$0(orcid)0000-0002-0904-9180$$aArdevines, Sandra$$uUniversidad de Zaragoza
000124419 245__ $$a1-Benzamido-1,4-dihydropyridine derivatives as anticancer agents: in vitro and in vivo assays
000124419 260__ $$c2023
000124419 5060_ $$aAccess copy available to the general public$$fUnrestricted
000124419 5203_ $$a1,4-Dihydropyridine is a privileged scaffold present in many bioactive molecules, from coenzymes to commercially available drugs. Among other interesting properties, it has been found good anticancer activity in some of these 1,4-DHPs, therefore many research groups are trying to develop new compounds based on this structural core.
For this purpose, in this work, a family of 23 new 1,4-dihydropyridines has been synthesized using hydrazide and malononitrile derivatives as precursors. This straightforward catalytic process has given rise to the desired products with moderate to excellent yields. All the compounds have been tested against four different cancer cell lines [HeLa (human cervical carcinoma), Jurkat (leukemia), A549 (human lung cancer) and MIA PaCa-2 (pancreatic cancer)] to establish a preliminary structure–activity relationship. From this study, and among the best candidates, we chose 4-chlorophenyl and 4-(trifluoromethyl)phenyl derivatives in the malononitrile ring to synthesize a second generation of molecules with enhanced cytotoxicity, modifying the substituent in the N-heterocyclic position (acylhydrazine moieties). With this second generation of compounds, we successfully decreased the IC50 until 7 µM.
An in-depth analysis of their biological properties suggests that these promising compounds trigger a non-conventional cell death mechanism known as paraptosis. Moreover, the tested photophysical properties of these products show in some cases an interesting long wavelength emission and excitation, potentially leading to new biosensors or theragnostic agents.
Finally, in vivo assays concerning the acute toxicity in mice of two of the most active compounds (with an alkyl chain of seven carbon atoms in the acylhydrazine moiety) demonstrated that even dosed at thousands fold the corresponding IC50 values (2500 and 3300 times more concentrated than the IC50 values for the two compounds studied), there was no sign of harmful effects on the tested subjects, results that support their use in further studies to discover new anticancer drugs.
000124419 536__ $$9info:eu-repo/grantAgreement/ES/DGA/E07-20R$$9info:eu-repo/grantAgreement/ES/AEI/PID2019-104379RB-C21$$9info:eu-repo/grantAgreement/ES/AEI/PID2020-117455GB-I00$$9info:eu-repo/grantAgreement/ES/DGA/B31-20R$$9info:eu-repo/grantAgreement/ES/MICINN-AEI/RED2018-102471-T$$9info:eu-repo/grantAgreement/ES/MICINN/RTI2018-097836-J-I00$$9info:eu-repo/grantAgreement/ES/MICINN/RYC-2018-025872-I
000124419 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000124419 590__ $$a5.3$$b2023
000124419 592__ $$a0.864$$b2023
000124419 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b66 / 231 = 0.286$$c2023$$dQ2$$eT1
000124419 593__ $$aChemistry (miscellaneous)$$c2023$$dQ1
000124419 593__ $$aChemical Engineering (miscellaneous)$$c2023$$dQ1
000124419 594__ $$a10.8$$b2023
000124419 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000124419 700__ $$0(orcid)0000-0002-3726-0493$$aAuria-Luna, Fernando
000124419 700__ $$aRomanos, Eduardo
000124419 700__ $$0(orcid)0000-0002-1218-7218$$aFernández-Moreira, Vanesa$$uUniversidad de Zaragoza
000124419 700__ $$aBenedi, Andrea$$uUniversidad de Zaragoza
000124419 700__ $$0(orcid)0000-0003-0553-0695$$aGimeno, M. Concepción
000124419 700__ $$0(orcid)0000-0002-2315-9079$$aMarzo, Isabel$$uUniversidad de Zaragoza
000124419 700__ $$0(orcid)0000-0001-6832-8983$$aMarqués-López, Eugenia$$uUniversidad de Zaragoza
000124419 700__ $$0(orcid)0000-0002-5244-9569$$aHerrera, Raquel P.
000124419 7102_ $$12010$$2760$$aUniversidad de Zaragoza$$bDpto. Química Inorgánica$$cÁrea Química Inorgánica
000124419 7102_ $$12013$$2765$$aUniversidad de Zaragoza$$bDpto. Química Orgánica$$cÁrea Química Orgánica
000124419 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000124419 773__ $$g16, 2 (2023), 104514 [22 pp.]$$pARABIAN JOURNAL OF CHEMISTRY$$tARABIAN JOURNAL OF CHEMISTRY$$x1878-5352
000124419 8564_ $$s3748628$$uhttps://zaguan.unizar.es/record/124419/files/texto_completo.pdf$$yVersión publicada
000124419 8564_ $$s2065026$$uhttps://zaguan.unizar.es/record/124419/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000124419 909CO $$ooai:zaguan.unizar.es:124419$$particulos$$pdriver
000124419 951__ $$a2024-11-22-12:00:05
000124419 980__ $$aARTICLE