La Química Orgánica: colección de materiales para el aprendizaje en un entorno abierto

Materiales creados para facilitar el autoestudio de la química Orgánica a nivel básico y medio, que se podrán implementar en una página web

Efficient inhibition of iron superoxide dismutase and of Trypanosoma cruzi growth by benzo[g]phthalazine derivatives functionalized with one or two imidazole rings

The synthesis and trypanosomatic behavior of a new series of 1,4-bis(alkylamino)benzo[g]phthalazines 1−4 containing the biologically significant imidazole ring are reported. In vitro antiparasitic activity against Trypanosoma cruzi epimastigotes is remarkable, especially for compound 2, whereas toxicity against Vero cells is very low. Conversion of epimastigotes to metacyclic forms in the presence of the tested compounds causes significant decreases in the amastigote and trypomastigote numbers. Fe-SOD inhibition is noteworthy, whereas effect on human Cu/Zn-SOD is negligible.The authors thank the Spanish CICYT for the financial support

1,4-Bis(alkylamino)benzo[g]phthalazines able to form dinuclear complexes of Cu(II) which as free ligands behave as SOD inhibitors and show efficient in vitro activity against Trypanosoma cruzi

The synthesis of a new series of 1,4-bis(alkylamino)benzo[g]phthalazines 1–3 is reported, and their ability to form dinuclear complexes with Cu(II) assayed. The geometry of the complexes is dependent on the nature of the electron-donor sites at the sidechains. Compounds 1 and 2, that contain sp3 or sp2 nitrogens at the end of the alkylamino groups, originate monopodal dinuclear complexes which seem to include endogenous OH bridges, and the sidechains seem to actively participate in complexation. However, the substitution of nitrogen by oxygen in 3 leads to a tripodal dinuclear complex in which the sidechains are not involved. The in vitro antiparasitic activity on Trypanosoma cruzi epimastigotes and amastigotes and the SOD activity inhibition have been evaluated for compounds 1–3, and, as expected, 1 and 2 show in all cases relevant results, whereas 3 is always the less active among the three substrates tested.The authors thank the Spanish Comision Interministerial de Ciencia y Tecnologia for the economical support given to this work (SAF99-0066)

In vivo trypanosomicidal activity of imidazole- or pyrazole-based benzo[ g ]phthalazine derivatives against acute and chronic phases of chagas disease

The in vivo trypanosomicidal activity of the imidazole-based benzo[g]phthalazine derivatives 1−4 and of the new related pyrazole-based compounds 5 and 6 has been studied in both the acute and chronic phases of Chagas disease. As a rule, compounds 1−6 were more active and less toxic than benznidazole in the two stages of the disease, and the monosubstituted derivatives 2, 4, and 6 were more effective than their disubstituted analogs. Feasible mechanisms of action of compounds 1−6 against the parasite have been explored by considering their inhibitory effect on the Fe-SOD enzyme, the nature of the excreted metabolites and the ultrastructural alterations produced. A complementary histopathological analysis has confirmed that the monosubstituted derivatives are less toxic than the reference drug, with the behavior of the imidazole-based compound 4 being especially noteworthy.The authors thank the Santander-Universidad Complutense Research Program (Grant GR58/08-921371-891), the Spanish MEC Project (Grant CGL2008-03687-E/BOS), and the MCINN Projects (CTQ2009-14288-C04-01 and Consolider CSD2010-00065) for financial support

Diazapolycyclic compounds. XXVII. On the selective hydrogenation of benzo[g]phthalazine‐1,4‐dione and 5‐methoxybenzo[g]phthalazine‐1,4‐dione adducts

A number of diazapolycyclic structures obtained by cycloaddition reaction of benzo[g]phthalazine-1,4-dione with several 1,3-dienes have been catalytically hydrogenated on palladium over charcoal. In a first step the double bond formed in the cycloaddition was reduced, except in the case of tetrasubstitution. The use of longer reaction times led to the selective reduction of the terminal aromatic rings, although the presence of the 5-methoxy substituent favored tetrahydropyridazine ring opening and prevented aromatic ring reduction. The stereochemical features of new compounds obtained are commented on the basis of X-ray and nmr data

Synthesis of Alkylamino Derivatives of 1, 4, 6, 11-Tetrahydropyridazino[1, 2-b]phthalazine-6, 11-dione

The synthesis of 7-[(3-N, N-dimethylamino)propylamino]-1, 4, 6, 11-tetrahydropyridazino[1, 2-b]phthalazine-6, 11-dione derivatives is reported. The expected monoalkylamino substituted derivative (4a) was obtained from the 7-chloro-substituted compound (3a), whereas the 7, 10-dichloro-substituted compound (3b) gave a mixture of the monoalkylamino derivative (4b) and the dialkylaminophthalimide (4c). The cytotoxic activity of 4a-c against HeLa cells was assayed. Compounds 4a and 4b showed a higher cytotoxicity than the starting adducts (3a and 3b).Peer reviewe

Synthesis of alkylamino derivatives of 1,4,6,11-tetrahydropyridazino[1,2-b]phthalazine-6,11-dione

The synthesis of 7-[(3-N,N-dimethylamino)propylamino]-1,4,6,11-tetrahydropyridazino[1,2 -b]phthalazine-6,11-dione derivatives is reported. The expected monoalkylamino substituted derivative (4a) was obtained from the 7-chloro-substituted compound (3a), whereas the 7,10-dichloro-substituted compound (3b) gave a mixture of the monoalkylamino derivative (4b) and the dialkylaminophthalimide (4c). The cytotoxic activity of 4a-c against HeLa cells was assayed. Compounds 4a and 4b showed a higher cytotoxicity than the starting adducts (3a and 3b)

Diazapolycyclic Compounds; XXV. Improved Synthesis of 6-Substituted 2,3-Dihydrobenzo[g]phthalazine-1,4-dione Derivatives

Peer reviewe

Creación de materiales de apoyo para la enseñanza de la química en la licenciatura en Biología

Se presentan en este trabajo una serie de materiales que se han elaborado para facilitar y mejorar el proceso de aprendizaje de la asignatura de Química por parte de los estudiantes que cursan la licenciatura en Biología, teniendo siempre presente la posibilidad de su utilización en otros estudios del área de Ciencias de la Salud. Estos materiales se han hecho accesibles a los alumnos dentro del Campus Virtual