Anti-Leishmania activity and molecular docking of unusual flavonoids-rich fraction from Arrabidaea brachypoda (Bignoniaceae)

Monica A das Neves; Jessyane R do Nascimento; Vera Lucia Maciel-Silva; Alberto M Dos Santos; Jaldyr de Jesus G V Junior; Ana Jessica S Coelho; Mayara Ingrid S Lima; Silma Regina F Pereira; Cláudia Q da Rocha

doi:10.1016/j.molbiopara.2024.111629

Anti-Leishmania activity and molecular docking of unusual flavonoids-rich fraction from Arrabidaea brachypoda (Bignoniaceae)

Mol Biochem Parasitol. 2024 May 13:259:111629. doi: 10.1016/j.molbiopara.2024.111629. Online ahead of print.

Authors

Monica A das Neves¹, Jessyane R do Nascimento², Vera Lucia Maciel-Silva³, Alberto M Dos Santos⁴, Jaldyr de Jesus G V Junior⁵, Ana Jessica S Coelho⁶, Mayara Ingrid S Lima⁶, Silma Regina F Pereira⁶, Cláudia Q da Rocha⁷

Affiliations

¹ UFMA-Federal University of Maranhão, Center for Exact Sciences and Technology (CCET), Post Graduate Program in Chemistry, São Luís CEP 65080-805, Brazil.
² UNESP, São Paulo State University Júlio de Mesquita Filho, Institute of Chemistry, Post Graduate Program in Chemistry, Araraquara CEP 14800-060, Brazil.
³ UEMA, Maranhão State University, Center for Education, Exact and Natural Sciences (CECEN), Department of Biology, CEP: 65055-310, São Luís, Brazil.
⁴ UNICAMP - University of Campinas, Institute of Chemistry and Center for Computer in Engineering and Sciences, Campinas CEP 13084-862, Brazil.
⁵ UFMA-Federal University of Maranhão, University College (COLUN), São Luís CEP 65080-805, Brazil.
⁶ UFMA-Federal University of Maranhão, Laboratory of Genetics and Molecular Biology, Department of Biology, São Luís CEP 65080-805, Brazil.
⁷ UFMA-Federal University of Maranhão, Center for Exact Sciences and Technology (CCET), Post Graduate Program in Chemistry, São Luís CEP 65080-805, Brazil. Electronic address: rocha.claudia@ufma.br.

PMID: 38750697
DOI: 10.1016/j.molbiopara.2024.111629

Abstract

Leishmaniases comprise a group of infectious parasitic diseases caused by various species of Leishmania and are considered a significant public health problem worldwide. Only a few medications, including miltefosine, amphotericin B, and meglumine antimonate, are used in current therapy. These medications are associated with severe side effects, low efficacy, high cost, and the need for hospital support. Additionally, there have been occurrences of drug resistance. Additionally, only a limited number of drugs, such as meglumine antimonate, amphotericin B, and miltefosine, are available, all of which are associated with severe side effects. In this context, the need for new effective drugs with fewer adverse effects is evident. Therefore, this study investigated the anti-Leishmania activity of a dichloromethane fraction (DCMF) extracted from Arrabidaea brachypoda roots. This fraction inhibited the viability of L. infantum, L. braziliensis, and L. Mexicana promastigotes, with IC₅₀ values of 10.13, 11.44, and 11.16 µg/mL, respectively, and against L. infantum amastigotes (IC₅₀ = 4.81 µg/mL). Moreover, the DCMF exhibited moderate cytotoxicity (CC₅₀ = 25.15) towards RAW264.7 macrophages, with a selectivity index (SI) of 5.2. Notably, the DCMF caused damage to the macrophage genome only at 40 µg/mL, which is greater than the IC₅₀ found for all Leishmania species. The results suggest that DCMF demonstrates similar antileishmanial effectiveness to isolated brachydin B, without causing genotoxic effects on mammalian cells. This finding is crucial because the isolation of the compounds relies on several steps and is very costly while obtaining the DCMF fraction is a simple and cost-effective process. Furthermore, In addition, the potential mechanisms of action of brachydins were also investigated. The computational analysis indicates that brachydin compounds bind to the Triosephosphate isomerase (TIM) enzyme via two main mechanisms: destabilizing the interface between the homodimers and interacting with catalytic residues situated at the site of binding. Based on all the results, DCMF exhibits promise as a therapeutic agent for leishmaniasis due to its significantly reduced toxicity in comparison to the adverse effects associated with current reference treatments.

Keywords: Cytotoxicity; Dimeric flavonoids; Genotoxicity; Leishmaniases; Molecular docking.