دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Anti-Leishmania activity and molecular docking of unusual flavonoids-rich fraction from Arrabidaea brachypoda (Bignoniaceae).
المؤلفون: das Neves MA; UFMA-Federal University of Maranhão, Center for Exact Sciences and Technology (CCET), Post Graduate Program in Chemistry, São Luís CEP 65080-805, Brazil., do Nascimento JR; UNESP, São Paulo State University Júlio de Mesquita Filho, Institute of Chemistry, Post Graduate Program in Chemistry, Araraquara CEP 14800-060, Brazil., Maciel-Silva VL; UEMA, Maranhão State University, Center for Education, Exact and Natural Sciences (CECEN), Department of Biology, CEP: 65055-310, São Luís, Brazil., Dos Santos AM; UNICAMP - University of Campinas, Institute of Chemistry and Center for Computer in Engineering and Sciences, Campinas CEP 13084-862, Brazil., Junior JJGV; UFMA-Federal University of Maranhão, University College (COLUN), São Luís CEP 65080-805, Brazil., Coelho AJS; UFMA-Federal University of Maranhão, Laboratory of Genetics and Molecular Biology, Department of Biology, São Luís CEP 65080-805, Brazil., Lima MIS; UFMA-Federal University of Maranhão, Laboratory of Genetics and Molecular Biology, Department of Biology, São Luís CEP 65080-805, Brazil., Pereira SRF; UFMA-Federal University of Maranhão, Laboratory of Genetics and Molecular Biology, Department of Biology, São Luís CEP 65080-805, Brazil., da Rocha CQ; 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.
المصدر: Molecular and biochemical parasitology [Mol Biochem Parasitol] 2024 Sep; Vol. 259, pp. 111629. Date of Electronic Publication: 2024 May 13.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 8006324 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-9428 (Electronic) Linking ISSN: 01666851 NLM ISO Abbreviation: Mol Biochem Parasitol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press.
مواضيع طبية MeSH: Bignoniaceae*/chemistry , Antiprotozoal Agents*/pharmacology , Antiprotozoal Agents*/chemistry , Antiprotozoal Agents*/isolation & purification , Flavonoids*/pharmacology , Flavonoids*/chemistry , Molecular Docking Simulation* , Leishmania*/drug effects , Leishmania*/genetics , Plant Extracts*/pharmacology , Plant Extracts*/chemistry , Plant Extracts*/isolation & purification, Animals ; Mice ; Inhibitory Concentration 50 ; Macrophages/drug effects ; Macrophages/parasitology ; RAW 264.7 Cells
مستخلص: 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 IC 50 values of 10.13, 11.44, and 11.16 µg/mL, respectively, and against L. infantum amastigotes (IC 50 = 4.81 µg/mL). Moreover, the DCMF exhibited moderate cytotoxicity (CC 50 = 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 IC 50 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Cytotoxicity; Dimeric flavonoids; Genotoxicity; Leishmaniases; Molecular docking
المشرفين على المادة: 0 (Antiprotozoal Agents)
0 (Flavonoids)
0 (Plant Extracts)
تواريخ الأحداث: Date Created: 20240516 Date Completed: 20240617 Latest Revision: 20240617
رمز التحديث: 20240619
DOI: 10.1016/j.molbiopara.2024.111629
PMID: 38750697
قاعدة البيانات: MEDLINE
الوصف
تدمد:1872-9428
DOI:10.1016/j.molbiopara.2024.111629