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Molecules 2017, 22(11), 1864; doi:10.3390/molecules22111864

Synthesis and Biological Evaluation of 2H-Indazole Derivatives: Towards Antimicrobial and Anti-Inflammatory Dual Agents

1
Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Xochimilco (UAM-X), Ciudad de México 04960, Mexico
2
Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias-Pediatría, IMSS, Ciudad de México 06720, Mexico
3
Catedrático CONACYT comisionado a Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Xochimilco (UAM-X), Ciudad de México 04960, Mexico
4
Facultad de Química, Departamento de Biología, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico
*
Author to whom correspondence should be addressed.
Received: 8 October 2017 / Revised: 27 October 2017 / Accepted: 27 October 2017 / Published: 31 October 2017
(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)
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Abstract

Indazole is considered a very important scaffold in medicinal chemistry. It is commonly found in compounds with diverse biological activities, e.g., antimicrobial and anti-inflammatory agents. Considering that infectious diseases are associated to an inflammatory response, we designed a set of 2H-indazole derivatives by hybridization of cyclic systems commonly found in antimicrobial and anti-inflammatory compounds. The derivatives were synthesized and tested against selected intestinal and vaginal pathogens, including the protozoa Giardia intestinalis, Entamoeba histolytica, and Trichomonas vaginalis; the bacteria Escherichia coli and Salmonella enterica serovar Typhi; and the yeasts Candida albicans and Candida glabrata. Biological evaluations revealed that synthesized compounds have antiprotozoal activity and, in most cases, are more potent than the reference drug metronidazole, e.g., compound 18 is 12.8 times more active than metronidazole against G. intestinalis. Furthermore, two 2,3-diphenyl-2H-indazole derivatives (18 and 23) showed in vitro growth inhibition against Candida albicans and Candida glabrata. In addition to their antimicrobial activity, the anti-inflammatory potential for selected compounds was evaluated in silico and in vitro against human cyclooxygenase-2 (COX-2). The results showed that compounds 18, 21, 23, and 26 display in vitro inhibitory activity against COX-2, whereas docking calculations suggest a similar binding mode as compared to rofecoxib, the crystallographic reference. View Full-Text
Keywords: anticandidal; indazole; Entamoeba histolytica; Giardia intestinalis; rational drug design; Trichomonas vaginalis anticandidal; indazole; Entamoeba histolytica; Giardia intestinalis; rational drug design; Trichomonas vaginalis
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MDPI and ACS Style

Pérez-Villanueva, J.; Yépez-Mulia, L.; González-Sánchez, I.; Palacios-Espinosa, J.F.; Soria-Arteche, O.; Sainz-Espuñes, T.R.; Cerbón, M.A.; Rodríguez-Villar, K.; Rodríguez-Vicente, A.K.; Cortés-Gines, M.; Custodio-Galván, Z.; Estrada-Castro, D.B. Synthesis and Biological Evaluation of 2H-Indazole Derivatives: Towards Antimicrobial and Anti-Inflammatory Dual Agents. Molecules 2017, 22, 1864.

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