Browsing by Author "Rivera, Gildardo"
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- ItemExpanding the chemical space of aryloxy-naphthoquinones as potential anti-Chagasic agents: synthesis and trypanosomicidal activity(SPRINGER BIRKHAUSER, 2021) Becerra, Nohemi A.; Espinosa Bustos, Christian; Vazquez, Karina; Rivera, Gildardo; Paulino, Margot; Cantero, Jorge; Nogueda, Benjamin; Chacon Vargas, Fabiola; Castillo Velazquez, Uziel; Elizondo Rodriguez, Ana F.; Toledo, Sofia; Moreno Rodriguez, Adriana; Aranda, Mario; Salas, Cristian O.In continuation our effort to research the chemical space of aryloxy-naphthoquinones as potential anti-Chagas agents, we synthesized nine derivatives and these compounds were evaluated in vitro against the epimastigote and trypomastigote forms of Mexican strains of Trypanosoma cruzi (T. cruzi). Most of these derivatives are highly active against epimastigote forms (IC50 < 1.0 mu M) compared to the reference drug benznidazole (Bzn). Then these were evaluated on trypomastigotes, which is showing better potency results than Bzn for compounds 3b and 3g. In addition, the cytotoxicity of these compounds was determined on the murine macrophage cell line J774. 3b and 3i were the most selective compounds against NINOA trypomastigote and INC-5 epimastigote forms, respectively. Further these compounds also have good oral bioavailability according to theoretical predictions. Finally, we were able to determine optimal substitution patterns using pharmacophoric models. All these results are provided very useful structural information to continue our designing of naphthoquinone derivatives against T. cruzi.
- ItemIn 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, VirgilioBackground: 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
- ItemNatural and Synthetic Naphthoquinones as Potential Anti-Infective Agents(2021) Ortiz Perez, Eyra; Rivera, Gildardo; Salas Sánchez, Cristián Osvaldo; Zarate Ramos, Juan J.; Trofymchuk, Oleksandra S.; Hernandez Soberanis, Lucio; Perales Flores, Juanita D.; Vazquez, KarinaBackground: Naphthoquinones are a class of aromatic compounds relevant for their chemical characteristics, structural properties, and biological activity. These compounds are found in nature with a wide range of effects, highlighting their antibacterial, antifungal, and antiprotozoal properties. Additionally, naphthoquinones are used as a scaffold to obtain new derivatives with pharmacological potential, mainly compounds against parasitic diseases. Objective: The purpose of this work was to carry out a comprehensive review of naphthoquinones and their derivatives obtained from both natural and synthetic sources, also, to analyze their biological activity against Leishmania spp. (Leishmaniasis), Trypanosoma cruzi (Chagas disease), Plasmodium falciparum (Malaria), Toxoplasma gondii (Toxoplasmosis), and Toxocara canis (Toxocariasis). All of these agents are responsible for relevant diseases worldwide. Results: Natural naphthoquinones, such as plumbagin, diospyrin, burmanin, lapachol, lawsone and psychorubrin, show an antiprotozoal activity similar or enhanced antiprotozoal activity to reference drugs. Some naphthoquinones obtained by synthesis or semi-synthesis showed better biological activity or less toxic effects than natural compounds. Conclusion: In this review, natural and synthetic naphthoquinones showed antiparasitic activity, in most cases, with improved results than current drugs currently used in clinical trials. A modification of their structure with different functional groups can enhance their biological effects, improve solubility, and reduce undesirable side effects. Therefore, naphthoquinones are important molecules in the development of new chemotherapeutic agents against parasitic diseases.
- ItemNew Inhibitors of Bcr-Abl Based on 2,6,9-Trisubstituted Purine Scaffold Elicit Cytotoxicity in Chronic Myeloid Leukemia-Derived Cell Lines Sensitive and Resistant to TKIs(2024) Delgado, Thalía; Veselá, Denisa; Dostálová, Hana; Krystof, Vladimir; Vojáčková, Veronika; Jorda, Radek; Castro-Alvarez, Alejandro; Bertrand, Jean Luc; Rivera, Gildardo; Faúndez, M.; Strnad, Miroslav; Espinosa-Bustos, Christian; Salas, Cristian