Expanding the chemical space of ester of quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives as potential antitubercular agents.

Tuberculosis is a worldwide health problem that warrants attention given that the current treatment options require a long-term chemotherapeutic period and have reported the development of Mycobacterium tuberculosis (M. tuberculosis) multidrug resistant strains. In this study, n-butyl and isobutyl quinoxaline-7-carboxylate 1,4-di-N-oxide were evaluated against replicating and non-replicating H37Rv M. tuberculosis strains. The results showed that seventeen of the twenty-eight derivatives have minimum inhibitory concentration (MIC) values lower than isoniazid (2.92 µM). The most active antimycobacterial agents were T-148, T-149, T-163, and T-164, which have the lowest MIC values (0.53, 0.57, 0.53, and 0.55 µM respectively). These results confirm the potential of quinoxaline-1,4-di-N-oxide against M. tuberculosis to develop and obtain new and more safety antituberculosis drugs.

A Computational Approach Using α-Carbonic Anhydrase to Find Anti-Trypanosoma cruzi Agents.

BACKGROUND: Chagas disease has an ineffective drug treatment despite efforts made over the last four decades. The carbonic anhydrase of Trypanosoma cruzi (α-TcCA) has emerged as an interesting target for the design of new antiparasitic compounds due to its crucial role in parasite processes. OBJECTIVE: The aim of this study was to identify potential α-TcCA inhibitors with trypanocide activity. METHOD: A maximum common substructure (MCS) and molecular docking were used to carry out a ligand- and structure-based virtual screening of ZINC20 and MolPort databases. The compounds selected were evaluated in an in vitro model against the NINOA strain of Trypanosoma cruzi, and cytotoxicity was determined in a murine model of macrophage cells J774.2. RESULTS: Five sulfonamide derivatives (C7, C9, C14, C19, and C21) had the highest docking scores (-6.94 to -8.31 kcal/mol). They showed key residue interactions on the active site of the α-TcCA and good biopharmaceutical and pharmacokinetic properties. C7, C9, and C21 had half-maximal inhibitory concentration (IC50) values of 26, 61.6, and 49 µM, respectively, against NINOA strain epimastigotes of Trypanosoma cruzi. CONCLUSION: Compounds C7, C9, and C21 showed trypanocide activity; therefore, these results encourage the development of new trypanocidal agents based on their scaffold.

Comparative Analysis of a Secondary Metabolite Profile from Roots and Leaves of Iostephane heterophylla by UPLC-MS and GC-MS.

Iostephane heterophylla is a traditional Mexican medicinal plant and is an important source of secondary metabolites with antimicrobial and cytotoxic activity. The aim of this work was to conduct a comparative analysis of secondary metabolites of different roots and leaf extracts of I. heterophylla from two zones in Mexico using ultraperformance liquid chromatography (UPLC) and gas chromatography (GC) coupled with mass spectrometry (MS). Twelve secondary metabolites from roots were identified in the leaves. Five new molecular weight secondary metabolites not previously reported were found. Six bioactive metabolites were quantified (quercetin ≤0.151 mg/mL in root and ≤0.041 mg/mL in leaf; hesperidin ≤0.66 mg/mL in root and ≤0.173 mg/mL in leaf; epicatechin ≤0. 163 mg/mL in root and ≤0.664 mg/mL in leaf; caffeic acid ≤0.372 mg/mL in root and ≤0.393 mg/mL in leaf; chlorogenic acid ≤0.234 mg/mL in root and ≤0.328 mg/mL in leaf; and xanthorrhizol ≤0.667 mg/mL in root), and a selective extraction method was established: quercetin in root and leaf by reflux; hesperidin in leaf by Soxhlet and in leaf by reflux; chlorogenic acid in root by Soxhlet and in leaf by reflux; chlorogenic acid ≤0.234 mg/mL in root and ≤0.328 mg/mL in leaf by ultrasound-assisted extraction; epicatechin in root by ultrasound-assisted extraction; caffeic acid in root by reflux and in leaf by Soxhlet. The most efficient solvent was methanol. This study provides a new secondary metabolite profile found in the leaves of I. heterophylla, highlighting it is an essential source of three bioactive compounds: epicatechin, hesperidin, and quercetin.

In vitro antiparasitic and antibacterial evaluation of organic extracts of Salvadoran flora / Evaluación antiparasitaria y antibacterial in vitro de extractos orgánicos de la flora salvadoreña

Currently, in developing countries, parasitic and bacterial diseases as amebiasis, giardiasis, trichonomiasis, leishmaniasis, trypanosomiasis, tuberculosis, and nocardiasis are a public health problem. The pharmacological treatment for these diseases is not completely effective and causes several side effects in patients. Therefore, the search for new compounds with biological activity is very important to develop new drugs safely and more efficiently. In this study, different organic extracts obtained from thirty-seven species of the Salvadoran flora were evaluated in several in vitro models to determine their potential activity against five protozoa (Entamoeba histolytica, Giardia lamblia, Trichomonas vaginalis, Leishmania mexicana, and Trypanosoma cruzi) and three bacteria (Acinetobacter baumanni, Mycobacterium tuberculosis, and Nocardia brasiliensis). The results showed the activity of eight extracts with IC50values of less than 100 µg/mL against L. mexicanaand five extracts with MICs values less than <50 µg/mL against M. tuberculosis. Besides, seven plant species showed MICs ≤3.125 µg/mL against N. brasiliensis. Additionally, secondary metabolites (flavonoids and monoterpene oxygenate) previously reported as active were fingerprint by UPLC-MS to establish a potential correlation with the biological activity showed.

Actualmente, en los países en vías de desarrollo, enfermedades parasitarias y bacterianas como la amebiasis, giardiasis, trichonomiasis, leishmaniasis, tripanosomiasis, tuberculosis y nocardiasis son un problema de salud pública. El tratamiento farmacológico de estas enfermedades no es del todo eficaz y provoca varios efectos secundarios en los pacientes. Por lo tanto, la búsqueda de nuevos compuestos con actividad biológica es muy importante para desarrollar nuevos fármacos, seguros y eficaces. En este estudio se evaluaron diferentes extractos orgánicos obtenidos de treinta y siete especies de la flora salvadoreña en varios modelos in vitro para determinar su actividad potencial contra cinco parásitos (Entamoeba histolytica, Giardia lamblia, Trichomonas vaginalis, Leishmania mexicana y Trypanosoma cruzi) y tres bacterias (Acinetobacter baumanni, Mycobacterium tuberculosis y Nocardia brasiliensis). Los resultados mostraron la actividad de ocho extractos con valores de CI50 menores a 100 µg/mL contra L. mexicana y cinco extractos con valores de CIMs <50 µg/mL contra M. tuberculosis. Además, siete especies de plantas presentaron CIM ≤3,125 µg/mL frente a N. brasilienses. Finalmente, los metabolitos secundarios (flavonoides y monoterpenos oxigenados) previamente reportados como activos fueron determinados por UPLC-MS para establecer una posible correlación con la actividad biológica mostrada.