Promising hit compounds against resistant trichomoniasis: Synthesis and antiparasitic activity of 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles
| Autor: | Alexandra Ibáñez-Escribano, Nerea Vela, Felipe Reviriego, Cristina Fonseca-Berzal, Vicente J. Arán, Juan José Nogal-Ruiz, Alicia Gómez-Barrio, José Antonio Escario |
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| Přispěvatelé: | Ministerio de Ciencia, Innovación y Universidades (España) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Antiprotozoal agents
Indazoles Antiparasitic medicine.drug_class Clinical Biochemistry Resistance Drug Resistance Pharmaceutical Science Trichomonas Infections medicine.disease_cause 01 natural sciences Biochemistry Microbiology chemistry.chemical_compound Structure-Activity Relationship Drug Discovery medicine Trichomonas vaginalis Parasitología Molecular Biology Indazole Trichomoniasis Antiparasitic Agents Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Nitrogen heterocycles Organic Chemistry medicine.disease 0104 chemical sciences 010404 medicinal & biomolecular chemistry chemistry Molecular Medicine |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname E-Prints Complutense. Archivo Institucional de la UCM |
| Popis: | A series of 11 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles (2–12) has been prepared starting from 1-benzyl-5-nitroindazol-3-ol 13, and evaluated against sensitive and resistant isolates of the sexually transmitted protozoan Trichomonas vaginalis. Compounds 2, 3, 6, 9, 10 and 11 showed trichomonacidal profiles with IC < 20 µM against the metronidazole-sensitive isolate. Moreover, all these compounds submitted to cytotoxicity assays against mammalian cells exhibited low non-specific cytotoxic effects, except compounds 3 and 9 which displayed moderate cytotoxicity (CC = 74.7 and 59.1 µM, respectively). Those compounds with trichomonacidal effect were also evaluated against a metronidazole-resistant culture. Special mention deserve compounds 6 and 10, which displayed better IC values (1.3 and 0.5 µM respectively) than that of the reference drug (IC MTZ = 3.0 µM). The high activity of these compounds against the resistant isolate reinforces the absence of cross-resistance with the reference drug. The remarkable trichomonacidal results against resistant T. vaginalis isolates suggest the interest of 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles to be considered as good prototypes to continue in the development of new drugs with enhanced trichomonacidal activity, aiming to increase the non-existent drugs to face clinical resistance efficiently for those patients in whom therapy with 5-nitroimidazoles is contraindicated. This work was partly supported by the Spanish Ministry of Science, Innovation and Universities (MICIU, ref. RTI2018-093940-BI00), and by the UCM Research Group (ref. 911120: Diagnosis, Epidemiology and Antiparasitic Therapy). |
| Databáze: | OpenAIRE |
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