Calanolides E1 and E2, two related coumarins from Calophyllum brasiliense Cambess. (Clusiaceae), displayed in vitro activity against amastigote forms of Trypanosoma cruzi and Leishmania infantum

Abstract

In the present work, the MeOH extract from stem barks of Calophyllum brasiliense Cambess. (Clusiaceae) displayed activity against amastigote forms of Trypanosoma cruzi and Leishmania infantum and was subjected to a bioactivity-guided fractionation to give two related coumarins - calanolides E1 (1) and E2 (2). Compounds 1 and 2 were actives to T. cruzi with EC₅₀ values of 12.1 and 8.2 μM, respectively. When tested against L. infantum, the EC₅₀ values were 37.1 and 29.1 μM, respectively. Compound 2, corresponding to anti isomer, showed the best selectivity index (SI) with values >24.4 to T. cruzi and >6.9 to L. infantum in comparison to the syn isomer 1. Furthermore, using an in silico multi-parametric prediction, both compounds did not contain any PAINS sub-structures. Therefore, these data suggest that coumarins 1 and 2 may contribute as scaffolds for the design of novel drug candidates for leishmaniasis and Chagas disease.

Graphical Abstract

Keywords:

• Calophyllum brasiliense Cambess.
• Clusiaceae
• coumarins
• Trypanosoma cruzi
• Leishmania infantum

Acknowledgments

The authors are grateful for the financial support and fellowships provided by CAPES, CNPq and FAPESP (2018/07885-1 and 2018/10279-6) as well as to Prof. Dr. Eliana Rodrigues by the collection of vegetable material. This publication is part of the activities of the Research Network Natural Products against Neglected Diseases (ResNetNPND): http://www.uni-muenster.de/ResNetNPND/. J.H.G.L., A.G.T. and P.S. thank CNPq for the scientific awards.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; Fundação de Amparo à Pesquisa do Estado de São Paulo;