In vitro trichomonacidal activity and preliminary in silico chemometric studies of 5-nitroindazolin-3-one and 3-alkoxy-5-nitroindazole derivatives

Parasitology
Alexandra Ibáñez-EscribanoJosé Antonio Escario

Abstract

A selection of 1,2-disubstituted 5-nitroindazolin-3-ones (1-19) and 3-alkoxy-5-nitroindazoles substituted at positions 1 (20-24) or 2 (25-39) from our in-house compound library were screened in vitro against the most common curable sexually transmitted pathogen, Trichomonas vaginalis. A total of 41% of the studied molecules (16/39) achieved a significant activity of more than 85% growth inhibition at the highest concentration assayed (100 µg mL(-1)). Among these compounds, 3-alkoxy-5-nitroindazole derivatives 23, 24, 25 and 27 inhibited parasite growth by more than 50% at 10 µg mL(-1). In addition, the first two compounds (23, 24) still showed remarkable activity at the lowest dose tested (1 µg mL(-1)), inhibiting parasite growth by nearly 40%. Their specific activity towards the parasite was corroborated by the determination of their non-specific cytotoxicity against mammalian cells. The four mentioned compounds exhibited non-cytotoxic profiles at all of the concentrations assayed, showing a fair antiparasitic selectivity index (SI > 7·5). In silico studies were performed to predict pharmacokinetic properties, toxicity and drug-score using Molinspiration and OSIRIS computational tools. The current in vitro results supported by...Continue Reading

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Citations

Mar 28, 2016·European Journal of Medicinal Chemistry·Cristina Fonseca-BerzalVicente J Arán
Feb 9, 2021·Bioorganic & Medicinal Chemistry Letters·Alexandra Ibáñez-EscribanoAlicia Gómez-Barrio

Related Concepts

Alkoxy
5-nitroindazole
Alcohols
Metazoa
Antitrichomonal Agents
Cell Survival
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In Silico
Indazoles
Structure-Activity Relationship

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