Synthesis and antiprotozoal activity of furanchalcone–quinoline, furanchalcone–chromone and furanchalcone–imidazole hybrids
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We report herein the synthesis and biological activities (cytotoxicity, leishmanicidal, and trypanocidal) of several furanchalcone–quinoline, furanchalcone–chromone, and furanchalcone–imidazole hybrids. The synthesized compounds were evaluated against amastigotes forms of L. (V) panamensis, which is the most prevalent Leishmania species in Colombia and against Trypanosoma cruzi, which is the major pathogenic species to humans. Cytotoxicity was evaluated against human U-937 macrophages. Compounds (6e, 8a–8f, 11b, and 11c) were active against both L. (V) panamensis and T. cruzi being 8e and 8f the most active compounds with an EC50 of 0.78 and 2.16 µM against L. (V) panamensis, respectively, and 0.66 and 0.72 µM against T. cruzi, respectively. Seven hybrid compounds showed better activity than meglumine antimoniate and the anti-trypanosomal activity of nine compounds were higher than benznidazole. Although these compounds showed toxicity for mammalian U-937 cells, they still have the potential to be considered as candidates for antileishmanial or trypanocydal drug development. There is not a clear relationship between the antiprotozoal activity and the length of the alkyl linker. However, we obtained higher bioactivity when the alkyl linker has nine and twelve carbon atoms. Furanchalcone-imidazole hybrids were the most active of all compounds, showing that the imidazole salt moiety is important for their biological actions.
KeywordsLeishmaniasis Chagas disease Antiprotozoal activity Furanchalcone Hybrids Quinoline
The authors thank Universidad de Antioquia (grant CODI 6203 and CIDEPRO) for financial support.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- Chatelain E, Ioset JR (2011) Drug discovery and development for neglected diseases: the DNDi model. Drug Des Dev Ther 5:175–181Google Scholar
- Coimbra ES, Antinarelli LM, Silva NP, Souza IO, Meinel RS, Rocha MN, Soares RP, da Silva AD (2016) Quinoline derivatives: synthesis, leishmanicidal activity and involvement of Mitochondrial oxidative stress as mechanism of action. Chem Biol Interact 260: 50–57Google Scholar
- Dos Santos WA, da Paz M, Ferreira AG, Piloto IC, Nakamura CV (2009) Chemical constituents from the roots of Spathelia excelsa and their antiprotozoal activity. J Braz Chem Soc 20:1089–1094Google Scholar
- Finney JD (1978) Probit analysis: statistical treatment of the sigmoid response curve, 3rd edn. Cambridge University Press, Cambridge, p 550Google Scholar
- Insuasty B, Ramirez J, Becerra D, Echeverry C, Quiroga J, Abonia R, Robledo SM, Velez ID, Upegui Y, Muñoz JA, Ospina V, Nogueras M, Cobo J (2015) An efficient synthesis of a new caffeine-based chalcones, pyrazolines and pyrazolo[3-4-b][1-4]diazepines as potential antimalarial, antitrypanosomal and antileishmanial agents. Eur J Chem Med 93:401–413CrossRefGoogle Scholar
- Lodish WH, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J (2016) Molecular cell biology, 8th edn. W. H. Freeman, New York, NY, p 273Google Scholar
- Nakayama H, Loiseau PM, Bories C, Torres de Ortiz S, Schinini A, Serna E, Rojas de Arias A, Fakhfakh MA, Franck X, Figasere B, Hocquemiller R, Fourner A (2005) Efficacy of orally administered 2-substituted quinolines in experimental murine cutaneous and visceral leishmaniases. Antimicrob Agents Chemother 49: 4950–4956Google Scholar
- Olmo F, Gómez-Contreras F, Navarro P, Marín C, Yunta MJR, Cano C, Campayo L, Martín-Oliva D, Rosales MJ, Sanchez-Moreno M (2015) Synthesis and evaluation of in vitro and in vivo trypanocidal properties of a new imidazole-containing nitrophthalazine derivative. Eur J Med Chem 106: 106–119Google Scholar
- Sánchez-Moreno M, Gómez-Contreras F, Navarro P, Marín C, Ramírez-Macías I, Olmo F, Sanz AM, Campayo L, Cano C, Yunta MJ (2012) In vitro leishmanicidal activity of imidazole- or pyrazole-based benzo[g]phthalazine derivatives against Leishmania infantum and Leishmania braziliensis species. J Antimicrob Chemother 67:387–397CrossRefPubMedGoogle Scholar
- Taylor VM, Cedeño DL, Muñoz DL, Jones MA, Lash TD, Young AM, Constantino MH, Esposito N, Vélez ID, Robledo SM (2011) In vitro and in vivo studies of the utility of dimethyl and diethyl carbaporphyrin ketals in treatment of cutaneous leishmaniasis. Antimicrob Agents Chemother 55:4755–4764CrossRefPubMedPubMedCentralGoogle Scholar
- World Health Organization (2013) http://www.who.int/features/qa/58/en/. Accessed 12 Dec 2013