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URI permanente para esta coleçãohttps://locus.ufv.br/handle/123456789/11800
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Item Natural abenquines and synthetic analogues: Preliminary exploration of their cytotoxic activity(Bioorganic & Medicinal Chemistry Letters, 2017-01-28) Nain-Perez, Amalyn; Barbosa, Luiz C.A.; Rodríguez-Hernández, Diego; Kramell, Annemarie E.; Heller, Lucie; Csuk, RenéIn this study, we explore the cytotoxic activity of four natural abenquines (2a–d) and fourteen synthetic analogues (2e–j and 3a–h) against a panel of six human cancer cell lines using a SRB assay. It was found that most of the compounds revealed higher levels of cytotoxic activities than naturally occurring abenquines. The analogues carrying ethylpyrrolidinyl and ethylpyrimidinyl with either an acetyl group (2 h–i) or a benzoyl group (3f–g), were the most potent against all human cancer cell lines and displayed EC50 between a range of 0.6–3.4 μM. Notably, of the compounds tested, compound 2i proved the most cytotoxic against both ovarian (A2780) and breast (MCF7) cells, showing EC50 = 0.6 and 0.8 μM respectively. Likewise, the analogues 2i, 3f and 3 g showed strong activity against cell HT29 with EC50 = 0.9 μM for these compounds.Item Leishmanicidal and cytotoxic activity of hederagenin-bistriazolyl derivatives(European Journal of Medicinal Chemistry, 2017-09-22) Rodríguez-Hernández, Diego; Barbosa, Luiz C.A.; Demuner, Antonio J.; Nain-Perez, Amalyn; Ferreira, Sebastião R.; Fujiwara, Ricardo T.; Almeida, Raquel M. de; Heller, Lucie; Csuk, RenéAiming to obtain new potent leishmanicidal and cytotoxic compounds from natural sources, the triterpene hederagenin was converted into several new 1,2,3-triazolyl derivatives tethered at C-23 and C-28. For this work hederagenin was isolated from fruits of Sapindus saponaria and reacted with propargyl bromide to afford as a major product bis-propargylic derivative 1 in 74%. Submitting this compound to Huisgen 1,3-dipolar cycloaddition reactions with several azides afforded the derivatives 2–19 with yields in the range of 40–87%. All compounds have been screened for in vitro cytotoxic activity in a panel of five human cancer cell lines by a SRB assay. The bioassays showed that compound 19 was the most cytotoxic against all human cancer cell lines with EC50 = 7.4–12.1 μM. Moreover, leishmanicidal activity was evaluated through the in vitro effect in the growth of Leishmania infantum, and derivatives 1, 2, 5 and 17 were highly effective preventing proliferation of intracellular amastigote forms of L. infantum (IC50 = 28.8, 25.9, 5.6 and 7.4 μM, respectively). All these compounds showed a higher selectivity index and low toxicity against two strains of kidney BGM and liver HepG2 cells. Compound 5 has higher selectivity (1780 times) in comparison with the commercial antimony drug and is around 8 times more selective than the most active compound previously reported hederagenin derivative. Such high activity associated with low toxicities make the new bis-traiazolyl derivatives promising candidates for the treatment of leishmaniasis. In addition, hederagenin and some derivatives (2, 5 and 17) showed interaction in the binding site of the enzyme CYP51Li.Item Synthesis of novel α-santonin derivatives as potential cytotoxic agents(European Journal of Medicinal Chemistry, 2010-10-23) Arantes, Francisco F.P.; Barbosa, Luiz C.A.; Maltha, Célia R.A.; Demuner, Antônio J.; Costa, PatriciaMarçal da; Ferreira, José R.O.; Costa-Lotufo, Letícia V.; Moraes, Manoel O.; Pessoa, CláudiaTen novel a -santonin derivatives have been synthesized as cytotoxic agents. The in vitro antitumor activity of these compounds has been evaluated against cancer cells lines. Structure-activity relationships indicate that a -methylene- g -lactone and endoperoxide functionalities play important roles in conferring cytotoxicity. The compounds 2e4, possessing the a -methylene- g -lactone group showed IC 50 values between 5.70 and 16.40 m M. Mixture of isomers 5 and 6, with the a -methylene- g -lactone and endoperoxide functionalities, displayed the greatest activity, with IC 50 values between 1.45 and 4.35 m M. The biological assays conducted with normal cells revealed that the compounds 2, 5 and 6 are selective against cancer cells lines tested. Bioactive lactones described herein and in our previous report did not cause disruption of the cell membrane in mouse erythrocytes.