Browsing by Author "Moreno-Rodriguez, Adriana"

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    2,3-Diketopiperazine as potential scaffold to develop new anti-Chagasic agents
    (2023) Osorio-Nieto, Urbano; Salas, Cristian O.; Mendez-Alvarez, Domingo; Rivera, Gildardo; Moreno-Rodriguez, Adriana; Perez-Cervera, Yobana; Castillo-Real, Lizet Monserrat; Espinosa-Bustos, Christian
    Continuing our program to develop compounds with potential activity against Trypanosoma cruzi, in this work we have designed and synthesized and evaluated in vitro on the trypomastigote form a new series of 2,3-diketopiperazines derivatives. By means of a two-step sequence, where one of them was a catalytic and selective C(sp(3))-H-bond reaction, nine final compounds (5a-i) were obtained. Most of these 2,3-diketopiperazines were highly active against the trypomastigote strain NINOA (LC50 < 100 mu M) compared to the reference drugs benznidazole (Bzn) and nifurtimox (Nfx). Likewise, compounds 5c and 5h showed high potency against the trypomastigote strain A1 (LC50 = 25.2 and 40.49 mu M, respectively), with 5c being four to five times more active than the reference drugs. In addition, the cytotoxicity of these compounds was determined in the murine macrophage J774 cell line, presenting in most cases, higher selectivity rates compared to Bzn and Nfx. In silico studies suggested that these 2,3-diketopiperazine derivatives could be inhibitors of the Fe-SOD enzyme at the cytosolic and mitochondrial level. Finally, these compounds would also have good oral bioavailability according to theoretical predictions.
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    In vitro and In vivo Biological Activity of Two Aryloxy-naphthoquinones in Mice Infected with Trypanosoma cruzi Strains
    (2024) Vazquez, Karina; Moreno-Rodriguez, Adriana; Dominguez-Diaz, Luis R.; Bertrand, Jeanluc; Salas, Cristian O.; Rivera, Gildardo; Cervera, Yobana Perez; Bocanegra-Garcia, Virgilio
    Background: Chagas disease, a condition caused by Trypanosoma cruzi, is an endemic disease in Latin American countries that affects approximately eight million people worldwide. It is a continuing public health problem. As nifurtimox and benznidazole are the two pharmacological treatments currently used to treat it, the present research proposes new therapeutic alternatives. Previous studies conducted on naphthoquinone derivatives have found interesting trypanocidal effects on epimastigotes, with the molecules 2-phenoxy-1,4-naphthoquinone (IC50= 50 nM and SI < 250) and 2-(3-nitrophenoxy)-naphthalene-1,4-dione (IC50= 20 nM y SI=625) presenting the best biological activity. Method: The present study evaluated the efficacy of in vitro, ex vivo and in vivo models of two aryloxyquinones, 2-phenoxy-1,4-naphthoquinone (1) and 2-(3-nitrophenoxy)-naphthalene-1,4- dione (2), against two Mexican T. cruzi strains in both their epimastigote and blood Trypomastigote stage. Both compounds were evaluated against T. cruzi using a mouse model (CD1) infected with Mexican isolates of T. cruzi, nifurtimox and benznidazole used as control drugs. Finally, the cytotoxicity of the two compounds against the J774.2 mouse macrophage cell line was also determined. Result: The in vitro and in vivo results obtained indicated that both quinones were more active than the reference drugs. Compound 1 presents in vivo activity, showing up to 40% parasite reduction after 8 h of administration, a finding which is 1.25 times more effective than the results obtained using nifurtimox. Conclusion: These are encouraging results for proposing new naphthoquinone derivatives with potential anti-T. cruzi activity