Synthesis and Biological Evaluation of 2H-Indazole Derivatives: Towards Antimicrobial and Anti-Inflammatory Dual Agents
AbstractIndazole 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
- Supplementary File 1:
Supplementary (PDF, 3765 KB)
Share & Cite This Article
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.
Pérez-Villanueva J, Yépez-Mulia L, González-Sánchez I, Palacios-Espinosa JF, Soria-Arteche O, Sainz-Espuñes TR, Cerbón MA, Rodríguez-Villar K, Rodríguez-Vicente AK, Cortés-Gines M, Custodio-Galván Z, Estrada-Castro DB. Synthesis and Biological Evaluation of 2H-Indazole Derivatives: Towards Antimicrobial and Anti-Inflammatory Dual Agents. Molecules. 2017; 22(11):1864.Chicago/Turabian Style
Pérez-Villanueva, Jaime; Yépez-Mulia, Lilián; González-Sánchez, Ignacio; Palacios-Espinosa, Juan F.; Soria-Arteche, Olivia; Sainz-Espuñes, Teresita R.; Cerbón, Marco A.; Rodríguez-Villar, Karen; Rodríguez-Vicente, Ana K.; Cortés-Gines, Miguel; Custodio-Galván, Zeltzin; Estrada-Castro, Dante B. 2017. "Synthesis and Biological Evaluation of 2H-Indazole Derivatives: Towards Antimicrobial and Anti-Inflammatory Dual Agents." Molecules 22, no. 11: 1864.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.