Benign-by-Design SAHA Analogues for Human and Animal Vector-Borne Parasitic Diseases

• Published in: ACS medicinal chemistry letters 2024-09, Vol.15 (9), p.1506-1515
• Main Authors: Rossi, Michele, Martinengo, Bianca, Diamanti, Eleonora, Salerno, Alessandra, Rizzardi, Nicola, Fato, Romana, Bergamini, Christian, Souza de Oliveira, Andressa, de Araújo Marques Ferreira, Thais, Andrade Holanda, Cleonice, Romeiro, Luiz Antonio Soares, Soeiro, Maria de Nazaré Correia, Nunes, Krislayne, Ferreira de Almeida Fiuza, Ludmila, Meuser Batista, Marcos, Fraga, Carlos A M, E A Alkhalaf, Hamed, Elmahallawy, Ehab Kotb, Ebiloma, Godwin U, De Koning, Harry P, Vittorio, Serena, Vistoli, Giulio, Blanquart, Christophe, Bertrand, Philippe, Bolognesi, Maria Laura
• Format: Article
• Language: English
• Subjects: Life Sciences
• ISSN: 1948-5875; 1948-5875
• DOI: 10.1021/acsmedchemlett.4c00242

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 - . 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 emerged as a green hit against the trypomastigote forms of . studies showed that the HDAC (TbDAC) catalytic pocket could be occupied with a similar binding mode by both SAHA and , providing a putative explanation for its antiparasitic mechanism of action ( , EC = 0.7 ± 0.2 μM).