000065304 001__ 65304
000065304 005__ 20190709135655.0
000065304 0247_ $$2doi$$a10.3390/molecules22122220
000065304 0248_ $$2sideral$$a104301
000065304 037__ $$aART-2017-104301
000065304 041__ $$aeng
000065304 100__ $$aJablonski, A.
000065304 245__ $$aCymantrenyl-nucleobases: Synthesis, anticancer, antitrypanosomal and antimicrobial activity studies
000065304 260__ $$c2017
000065304 5060_ $$aAccess copy available to the general public$$fUnrestricted
000065304 5203_ $$aThe synthesis of four cymantrene-5-fluorouracil derivatives (1-4) and two cymantrene-adenine derivatives (5 and 6) is reported. All of the compounds were characterized by spectroscopic methods and the crystal structure of two derivatives (1 and 6), together with the previously described cymantrene-adenine compound C was determined by X-ray crystallography. While the compounds 1 and 6 crystallized in the triclinic P-1 space group, compound C crystallized in the monoclinic P21/m space group. The newly synthesized compounds 1-6 were tested together with the two previously described cymantrene derivatives B and C for their in vitro antiproliferative activity against seven cancer cell lines (MCF-7, MCF-7/DX, MDA-MB-231, SKOV-3, A549, HepG2m and U-87-MG), five bacterial strains Staphylococcus aureus (methicillin-sensitive, methicillin-resistant and vancomycin-intermediate strains), Staphylococcus epidermidis, and Escherichia coli, including clinical isolates of S. aureus and S. epidermidis, as well as against the protozoan parasite Trypanosoma brucei. The most cytotoxic compounds were derivatives 2 and C for A549 and SKOV-3 cancer cell lines, respectively, with 50% growth inhibition (IC50) values of about 7 µM. The anticancer activity of the cymantrene compounds was determined to be due to their ability to induce oxidative stress and to trigger apoptosis and autophagy in cancer cells. Three derivatives (1, 4 and 5) displayed promising antitrypanosomal activity, with GI50 values in the low micromolar range (3-4 µM). The introduction of the 5-fluorouracil moiety in 1 enhanced the trypanocidal activity when compared to the activity previously reported for the corresponding uracil derivative. The antibacterial activity of cymantrene compounds 1 and C was within the range of 8-64 µg/mL and seemed to be the result of induced cell shrinking.
000065304 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000065304 590__ $$a3.098$$b2017
000065304 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b68 / 171 = 0.398$$c2017$$dQ2$$eT2
000065304 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b133 / 292 = 0.455$$c2017$$dQ2$$eT2
000065304 592__ $$a0.855$$b2017
000065304 593__ $$aAnalytical Chemistry$$c2017$$dQ1
000065304 593__ $$aPharmaceutical Science$$c2017$$dQ1
000065304 593__ $$aChemistry (miscellaneous)$$c2017$$dQ1
000065304 593__ $$aOrganic Chemistry$$c2017$$dQ2
000065304 593__ $$aPhysical and Theoretical Chemistry$$c2017$$dQ2
000065304 593__ $$aDrug Discovery$$c2017$$dQ2
000065304 593__ $$aMedicine (miscellaneous)$$c2017$$dQ2
000065304 593__ $$aMolecular Medicine$$c2017$$dQ3
000065304 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000065304 700__ $$aMatczak, K.
000065304 700__ $$aKoceva-Chyla, A.
000065304 700__ $$aDurka, K.
000065304 700__ $$aSteverding, D.
000065304 700__ $$aJakubiec-Krzesniak, K.
000065304 700__ $$aSolecka, J.
000065304 700__ $$aTrzybinski, D.
000065304 700__ $$aWozniak, K.
000065304 700__ $$0(orcid)0000-0002-6275-1104$$aAndreu, V.
000065304 700__ $$0(orcid)0000-0003-2293-363X$$aMendoza, G.
000065304 700__ $$0(orcid)0000-0003-3165-0156$$aArruebo, M.$$uUniversidad de Zaragoza
000065304 700__ $$aKochel, K.
000065304 700__ $$aKrawczyk, B.
000065304 700__ $$aSzczukocki, D.
000065304 700__ $$aKowalski, K.
000065304 7102_ $$15005$$2555$$aUniversidad de Zaragoza$$bDpto. Ing.Quím.Tecnol.Med.Amb.$$cÁrea Ingeniería Química
000065304 773__ $$g22, 12 (2017), 2220$$pMolecules$$tMolecules$$x1420-3049
000065304 8564_ $$s1647922$$uhttps://zaguan.unizar.es/record/65304/files/texto_completo.pdf$$yVersión publicada
000065304 8564_ $$s118154$$uhttps://zaguan.unizar.es/record/65304/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000065304 909CO $$ooai:zaguan.unizar.es:65304$$particulos$$pdriver
000065304 951__ $$a2019-07-09-12:45:48
000065304 980__ $$aARTICLE