Furanchalcone–biphenyl hybrids: synthesis, in silico studies, antitrypanosomal and cytotoxic activities
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The synthesis, antitrypanosomal, and cytotoxic activities of 17 furanchalcone derivatives are described herein. The structure of the synthesized products was elucidated by a combination of spectrometric analyses. The synthesized compounds were evaluated against Trypanosoma cruzi, which is the pathogenic species to humans. Cytotoxicity was evaluated against human U-937 macrophages. Eleven compounds were active against amastigotes of T. cruzi with EC50 values lower than 40 µM. Hybrids 7b–7d and 8a–8g showed better activity than benznidazole. Structure activity relationship (SAR) showed that the presence of electron withdrawing groups, such as nitro or fluorine, increased the activity and that the degree of oxygenation is essential for activity. In addition, molecular docking was used to identify a possible protein target for the designed compounds. A spearman correlation of 0.608 between the predicted scores and the experimental data profile the enzyme cruzipain as a potential candidate. Finally, in silico ADMET studies of the arylfuranchalcones showed that these novel compounds have suitable drug-like properties, making them potentially promising agents for antichagasic therapy.
KeywordsChagas disease Trypanosoma cruzi Furanchalcone Hybrids In silico studies Biphenyl
The authors thank Universidad de Antioquia (Grants CODI 6203 and CIDEPRO) for financial support.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Brun R, Bühler Y, Sandmeier U, Kaminsky R, Bacchi CJ, Rattendi D, Lane S, Croft SL, Snowdon D, Yardley V, Caravatti G, Frei J, Stanek J, Mett H (1996) In vitro trypanocidal activities of new S-adenosylmethionine decarboxylase inhibitors. Antimicrob Agents Chemother 40:1442–1447CrossRefGoogle Scholar
- Finney JD (1978) Probit Analysis: Statistical Treatment of the Sigmoid Response Curve, 3rd ed. Cambridge University Press, Cambridge, UK, 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
- Ma L, Chen J, Wang X, Liang X, Luo Y, Zhu W, Wang T, Peng M, Li S, Jie S, Peng A, Wei Y, Chen L (2011) Structural modification of honokiol, a biphenyl occurring in magnolia officinalis: the evaluation of honokiol analogues as inhibitors of angiogenesis and for their cytotoxicity and structure-activity relationship. J Med Chem 54:6469–6481CrossRefGoogle Scholar
- Meunier B (2008) Hybrid molecules with a dual mode of action: dream or reality? Acc Chem Res 41(69):77Google Scholar
- Patrick GL (2013) An Introduction to Medicinal Chemistry, fifth ed., Oxford University Press, pp. 1-14Google Scholar
- Sajid M, Robertson SA, Brinen LS, McKerrow JH (2011) Cruzain. In: Robinson MW, Dalton JP:Cysteine Proteases of Pathogenic Organisms, Springer, Boston, MA, pp. 100–115Google 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 55:4755–4764CrossRefGoogle Scholar
- Trott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31:455–461Google Scholar
- World Health Organization. Chagas disease (American Trypanosomiasis). http://www.who.int/news-room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis). Accessed 20 Jun 2018
- World Health Organization. Neglected tropical diseases. http://www.who.int/neglected_diseases/diseases/en/. Accessed 20 Jun 2018