Synthesis and biological evaluation of some novel 1-indanone thiazolylhydrazone derivatives as anti-Trypanosoma cruzi agents

• Published in: European journal of medicinal chemistry 2012-09, Vol.55, p.155-163
• Main Authors: Caputto, María E., Ciccarelli, Alejandra, Frank, Fernanda, Moglioni, Albertina G., Moltrasio, Graciela Y., Vega, Daniel, Lombardo, Elisa, Finkielsztein, Liliana M.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Trypanosoma cruzi compounds; Antiprotozoal Agents - chemical synthesis; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - toxicity; Biological and medical sciences; Cercopithecus aethiops; Chagas's disease; Chemistry Techniques, Synthetic; Hydrazones - chemical synthesis; Hydrazones - chemistry; Hydrazones - pharmacology; Hydrazones - toxicity; Life Cycle Stages - drug effects; Medical sciences; Microwave assisted synthesis; Miscellaneous; Pharmacology. Drug treatments; Sterols - biosynthesis; Thiazolylhydrazones; Trypanosoma cruzi - drug effects; Trypanosoma cruzi - growth & development; Trypanosoma cruzi - metabolism; Vero Cells
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2012.07.013

A series of novel 4-arylthiazolylhydrazones (TZHs) derived from 1-indanones were synthesized in good yields (66–92%) in a simple procedure using microwave irradiation and then characterized by spectroscopy studies. The compounds were evaluated for their in vitro anti-Trypanosoma cruzi activity against the epimastigote, trypomastigote and amastigote forms of the parasite. Most TZHs displayed excellent activity, and were more potent and selective than the reference drug Benznidazole, used in the current chemotherapy. Analysis of the free sterols from parasite incubated with the compounds showed that inhibition of ergosterol biosynthesis is a possible target for the action of these new TZHs. In particular, TZH 9 emerged as a promising antichagasic compound to be evaluated in animal models. Seventeen thiazolylhydrazones were prepared by microwave-assisted synthesis and screened for in vitro tripanosomicidal activity against the epimastigote, trypomastigote and amastigote forms of Trypanosoma cruzi. [Display omitted] ► Novel thiazolylhydrazones derived from 1-indanones were synthesized. ► The title compounds were evaluated for their in vitro anti-T. cruzi activity. ► The tested compounds showed excellent antichagasic activity. ► Thiazolylhydrazone 9 emerged as a promising antichagasic compound. ► Investigations on the possible mechanisms of action were performed.