| Full text | |
| Author(s): |
Bastos, Tanira Matutino
[1]
;
Russo, Helena Mannochio
[2]
;
Moretti, Nilmar Silvio
[3]
;
Schenkman, Sergio
[3]
;
Marcourt, Laurence
[2]
;
Gupta, Mahabir Prashad
[4]
;
Wolfender, Jean-Luc
[2]
;
Queiroz, Emerson Ferreira
[2]
;
Pereira Soares, Milena Botelho
[1]
Total Authors: 9
|
| Affiliation: | [1] Fiocruz MS, Inst Goncalo Moniz, BR-40296710 Salvador, BA - Brazil
[2] Univ Lausanne, Univ Geneva, CMU, EPGL, Sch Pharmaceut Sci, 1 Rue Michel Servet, CH-1211 Geneva - Switzerland
[3] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, BR-04039032 Sao Paulo, SP - Brazil
[4] Univ Panama, Coll Pharm, Ctr Pharmacognost Res Panamanian Flora CIFLORPAN, Panama City 082400172 - Panama
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | Molecules; v. 24, n. 7 APR 3 2019. |
| Web of Science Citations: | 1 |
| Abstract | |
Benznidazole and nifurtimox, the only drugs available for the treatment of Chagas disease, have limited efficacy and have been associated with severe adverse side effects. Thus, there is an urgent need to find new biotargets for the identification of novel bioactive compounds against the parasite and with low toxicity. Silent information regulator 2 (Sir2) enzymes, or sirtuins, have emerged as attractive targets for the development of novel antitrypanosomatid agents. In the present work, we evaluated the inhibitory effect of natural compounds isolated from cashew nut (Anacardium occidentale, L. Anacardiaceae) against the target enzymes TcSir2rp1 and TcSir2rp3 as well as the parasite. Two derivates of cardol (1, 2), cardanol (3, 4), and anacardic acid (5, 6) were investigated. The two anacardic acids (5, 6) inhibited both TcSir2rp1 and TcSir2rp3, while the cardol compound (2) inhibited only TcSir2rp1. The most potent sirtuin inhibitor active against the parasite was the cardol compound (2), with an EC50 value of 12.25 mu M, similar to that of benznidazole. Additionally, compounds (1, 4), which were inactive against the sirtuin targets, presented anti-T. cruzi effects. In conclusion, our results showed the potential of Anacardium occidentale compounds for the development of potential sirtuin inhibitors and anti-Trypanosoma cruzi agents. (AU) | |
| FAPESP's process: | 15/22031-0 - Cell signaling in Trypanosoma during host-parasite interaction |
| Grantee: | Sergio Schenkman |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 18/09948-0 - Study of protein acetylation in Leishmania |
| Grantee: | Nilmar Silvio Moretti |
| Support Opportunities: | Regular Research Grants |