Benign-by-Design SAHA Analogues for Human and Animal Vector-Borne Parasitic Diseases
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 <b>13</b>-<b>20</b>. 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 <b>13</b> emerged as a green hit against the trypomastigote forms of <i>T. b. brucei</i>. <i>In silico</i> studies showed that the <i>T. b. brucei</i> HDAC (TbDAC) catalytic pocket could be occupied with a similar binding mode by both SAHA and <b>13</b>, providing a putative explanation for its antiparasitic mechanism of action (<b>13</b>, EC<sub>50</sub> = 0.7 ± 0.2 μM).
Authors
- Andressa Souza de Oliveira (ORCID: https://orcid.org/0000-0001-5508-1184)
- Cleonice Andrade Holanda (ORCID: https://orcid.org/0000-0003-4588-3268)
- Marcos Meuser Batista (ORCID: https://orcid.org/0000-0003-4783-7011)
- Harry P. de Koning (ORCID: https://orcid.org/0000-0002-9963-1827)
- M. Soeiro (ORCID: https://orcid.org/0000-0002-4767-6468)
- Romana Fato (ORCID: https://orcid.org/0000-0002-8945-6826)
- Ludmila Ferreira de Almeida Fiuza (ORCID: https://orcid.org/0000-0001-6707-8556)
- Michele Rossi (ORCID: https://orcid.org/0000-0003-1121-324X)
- Serena Vittorio (ORCID: https://orcid.org/0000-0001-6092-5011)
- Godwin U. Ebiloma (ORCID: https://orcid.org/0000-0003-4072-9800)
- Giulio Vistoli (ORCID: https://orcid.org/0000-0002-3939-5172)
- Ehab Kotb Elmahallawy (ORCID: https://orcid.org/0000-0003-4484-3678)
- Alessandra Salerno (ORCID: https://orcid.org/0000-0003-0300-9062)
- Christophe Blanquart (ORCID: https://orcid.org/0000-0002-0917-3747)
- Eleonora Diamanti (ORCID: https://orcid.org/0000-0001-8392-5575)
- Nicola Rizzardi (ORCID: https://orcid.org/0000-0002-9294-7116)
- Philìppe Bertrand
- María Laura Bolognesi (ORCID: https://orcid.org/0000-0002-1289-5361)
- Luiz Antônio Soares Romeiro (ORCID: https://orcid.org/0000-0001-5679-0820)
- Carlos Alberto Manssour Fraga (ORCID: https://orcid.org/0000-0001-6733-7079)
- Thais de A. M. Ferreira
- Bianca Martinengo (ORCID: https://orcid.org/0000-0002-4239-8120)
- Christian Bergamini (ORCID: https://orcid.org/0000-0003-4387-5117)
- Krislayne Nunes
- Hamed E. Alkhalaf
Institutions
- Universidade Federal do Rio de Janeiro (BR)
- Centre National de la Recherche Scientifique (FR)
- Universidade de Brasília (BR)
- Inserm (FR)
- University of Milan (IT)
- Université de Poitiers (FR)
- Institut de Chimie des Milieux et des Matériaux de Poitiers (FR)
- Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers (FR)
- Université d'Angers (FR)
- Fundação Oswaldo Cruz (BR)
- University of Córdoba (ES)
- University of Salford (GB)
- University of Glasgow (GB)
- University of Bologna (IT)
- Nantes Université (FR)
- Sohag University (EG)
Publication Details
- Journal
- ACS Medicinal Chemistry Letters
- Published
- 2024-08-13
- DOI
- https://doi.org/10.1021/acsmedchemlett.4c00242
- Citations
- 4
- Primary Topic
- Research on Leishmaniasis Studies
- Type
- article
- Field-Weighted Citation Impact
- 2.17
Funders
- Universidade de Brasília
- University of Salford Manchester
- Università degli Studi di Milano
- Royal Society
- Academy of Medical Sciences
- European Commission
- University of Glasgow
- European Cooperation in Science and Technology
- Institut National de la Santé et de la Recherche Médicale
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
- Centre National de la Recherche Scientifique
- Fundação Oswaldo Cruz
- Philippine-American Educational Foundation
- Universidade Federal do Rio de Janeiro
- Universidad de Córdoba
- Ministero dell'Università e della Ricerca
- Université de Poitiers