We prepared a series of 10 carbamates derivatives based on two common antiprotozoal drugs: metronidazole (
-
) and secnidazole (
-
). The compounds were tested in vitro against a set of two ...amitochondriate protozoa:
and
. Compounds 1-10 showed strong antiprotozoal activities, with potency values in the low micromolar-to-nanomolar range, being more active than their parent drugs. Metronidazole carbamate (1) was the most active of the series, with nanomolar activities against G. duodenalis (IC
= 460 nM) and T. vaginalis (IC
= 60 nM). The potency of compound 1 was 10 times greater than that of metronidazole against both parasites. None of compounds showed in vitro cytotoxicity against VERO cells tested at 100 µM. Molecular dynamics of compounds 1-10, secnidazole, and metronidazole onto the ligand binding site of pyruvate-ferredoxin oxidoreductase of T. vaginalis and the modeled -tubulin of G. duodenalis revealed putative molecular interactions with key residues in the binding site of both proteins implicated in the mode of action of the parent drugs.
The stingless bee Melipona beecheii is experiencing colony decline due to floral resource scarcity caused by deforestation. A study was conducted to identify the floral resources used by M. beecheii ...using honey samples collected in four regions of the state of Campeche, Mexico. A melissopalynological analysis of sixteen collected honey samples identified 69 plant species from 24 families, and established that Fabaceae was the main plant family visited. Based on botanical origin, seven samples were classified as monofloral and nine as multifloral. The predominant species were Bursera simaruba, Lonchocarpus longistylus, Piscidia piscipula, Senna pallida and Senna racemosa. Shannon diversity index values (2.06–2.55) indicated moderate diversity in floral resources and Simpson diversity index values (0.82–0.89) indicated a moderate dominance of plant species in the studied regions. The results suggest M. beecheii is polylectic with some degree of specialization. The plant species identified as predominant in the studied honey samples are candidates for use in strategies intended to conserve the food resources used by M. beecheii on the Yucatan Peninsula.
We designed hybrid molecules between propamidine and benzimidazole in order to retain the antiprotozoal action, but decreasing the toxic effect of the molecule.
Design and prepare 12 hybrids for ...testing their antiparasitic effect over three protozoa: Giardia intestinalis, Trichomonas vaginalis and Leishmania mexicana, as well as conduct several in silico simulations such as toxicological profile, molecular docking and molecular dynamics in order to understand their potential mode of action.
Hybrids 1-3, 6-9 and 12 were obtained using a chemical pathway previously reported. Compounds 4, 5, 10 and 11 were prepared using a one-pot reduction-cyclization reaction. The in vitro antiparasitic and cytotoxic activities of these compounds were conducted. It was calculated several properties such as toxicity, PK behavior, as well as docking studies and molecular dynamics of the most active compound performed in a DNA sequence dodecamer in comparison with propamidine.
Compound 2 was 183, 127 and 202 times more active against G. intestinalis than metronidazole, pentamidine and propamidine. It was eleven times more active than pentamidine against L. mexicana. This compound showed low in vitro mammalian cytotoxicity. Molecular simulations showed a stable complex 2-DNA that occurred in the minor groove, analogous to propamidine-DNA complex.
Compound 2, exhibited the higher bioactivity, especially towards G. intestinalis and L. mexicana. This study demonstrated that the replacement of benzimidazole scaffold instead of toxic amidine group in propamidine, results in an enhancement of antiprotozoal bioactivity. The preliminary molecular dynamics simulation suggests that the ligand-DNA complex is stable.
The Omicron subvariant BA.1 of SARS-CoV-2 was first detected in November 2021 and quickly spread worldwide, displacing the Delta variant. In this work, a characterization of the spread of this ...variant in Mexico is presented.
The time to fixation of BA.1, the diversity of Delta sublineages, the population density, and the level of virus circulation during the inter-wave interval were determined to analyze differences in BA.1 spread.
BA.1 began spreading during the first week of December 2021 and became dominant in the next three weeks, causing the fourth COVID-19 epidemiological surge in Mexico. Unlike previous variants, BA.1 did not exhibit a geographically distinct circulation pattern. However, a regional difference in the speed of the replacement of the Delta variant was observed.
Viral diversity and the relative abundance of the virus in a particular area around the time of the introduction of a new lineage seem to have influenced the spread dynamics, in addition to population density. Nonetheless, if there is a significant difference in the fitness of the variants, or if the time allowed for the competition is sufficiently long, it seems the fitter virus will eventually become dominant, as observed in the eventual dominance of the BA.1.x variant in Mexico.
•TPEE has high content of antioxidant compounds.•Oral administration of TPEE decreased AST, ALT and total protein.•TPEE activates genes involved in both the antioxidant and antifibrotic pathways.•Our ...results suggest that TPEE may be a potentially hepatoprotective agent.
Hepatic cirrhosis is a neglected worldwide public health problem. Current hepatic cirrhosis treatment drugs remain inadequate and provide a poor prognosis. Research on alternative treatments has broadened to include active compounds from natural sources. Tradescantia pallida is a plant native to Mexico with high antioxidant content the activity of which has received only limited attention. The hepatoprotective activity of a Tradescantia pallida ethanol extract (TPEE) was evaluated through histopathology, and analysis of functional and biochemical parameters. Efficacy of the TPEE (50 mg/kg) was evaluated in a chronic CCl4-induced hepatotoxicity model in Wistar rats. Co-administration of the TPEE attenuated increases in alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and albumin (ALB) levels. Histopathology analysis supported the functional and biochemical observations. The TPEE upregulated genes that participate in antioxidant (NRF2 and NQO1) and antifibrotic (MMP-2 and TIMP-3) mechanisms in chronic CCl4-intoxicated rats. These findings suggest that this TPEE has beneficial hepatoprotective activity comparable to the standard hepatoprotective compound silymarin.
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