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oai:arca.fiocruz.br:icict/660962026-07-24T18:50:23Zcom_icict_1956col_icict_1957

Benign-by-design SAHA analogues for human and animal vector-borne parasitic diseases Rossi, Michele Martinengo, Bianca Diamanti, Eleonora Salerno, Alessandra Rizzardi, Nicola Fato, Romana Bergamini, Christian Oliveira, Andressa Souza de Ferreira, Thais de Araújo Marques Holanda, Cleonice Andrade Romeiro, Luiz Antonio Soares Soeiro, Maria de Nazaré Correia Costa, Krislayne Nunes da Fiuza, Ludmila Ferreira de Almeida Batista, Marcos Meuser Fraga, Carlos Alberto Manssour Alkhalaf, Hamed E. A. Elmahallawy, Ehab Kotb Ebiloma, Godwin U. de Koning, Harry P. Vittorio, Serena Vistoli, Giulio Blanquart, Christophe Bertrand, Philippe Bolognesi, Maria Laura Produção científica do Laboratório de Biologia Celular. The authors gratefully acknowledge support from National Council of Technological and Scientific Development (CNPq #401864/2013-8 (PVE), #312709/2017-0 (DT-2), and #308486/2020-0 (DT-2), from RPT11F (Rede de Plataformas Tecnológicas da Fiocruz, IOC/Fiocruz), from The Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ), CNPq, Oswaldo Cruz Foundation, PAEF/CNPq/Fiocruz, and CAPES, ChemAxon (https:// chemaxon.com) for kindly providing academic free license of Marvin suite. Maria de Nazaré Correia Soeiro is a research fellow from CNPq and CNE. This work was developed within the COST Action One Health drugs against parasitic vector-borne diseases in Europe and beyond (OneHealthdrugs) CA21111. The search for new drugs fulfilling One Health and Green Chemistry requirements is an urgent call. Here, for the first time, we envisaged developing SAHA analogues by starting from the cashew nutshell liquid (CNSL) agro-industrial waste and employing a metathesis approach. This sustainable combination (comprising principles #7 and #9) allowed a straightforward synthesis of compounds 13–20. All of them were found to not be toxic on HepG2, IMR-32, and L929 cell lines. Then, their potential against major human and animal vector-borne parasitic diseases (VBPDs) was assessed. Compound 13 emerged as a green hit against the trypomastigote forms of T. b. brucei. In silico studies showed that the T. b. brucei HDAC (TbDAC) catalytic pocket could be occupied with a similar binding mode by both SAHA and 13, providing a putative explanation for its antiparasitic mechanism of action (13, EC₅₀ = 0.7 ± 0.2 μM). 2024-09-25T17:44:02Z 2024-09-25T17:44:02Z 2024 journal article ROSSI, Michele et al. Benign-by-design SAHA analogues for human and animal vector-borne parasitic diseases. ACS Medicinal Chemistry Letters, v. 15, n. 9, p. 1506-1515, 13 Aug. 2024. 1948-5875 https://arca.fiocruz.br/handle/icict/66096 10.1021/acsmedchemlett.4c00242 eng restricted access application/pdf American Chemical Society