The structure design of biotransformed unsymmetrical nitro-contained 1,5-diaryl-3-oxo-1, 4-pentadienyls for the anti-parasitic activities

Autor(es)

Din, Zia Ud ^[1] ; Lazarin-Bidoia, Danielle ^[2] ; Kaplum, Vanessa ^[2] ; Garcia, Francielle Pelegrin ^[2] ; Nakamura, Celso Vataru ^[2] ; Rodrigues-Filho, Edson ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Carlos, Dept Quim, LaBioMMi, CP 676, BR-13565905 Sao Carlos, SP - Brazil

^[2] Univ Estadual Maringa, Lab Inovacao Tecnol Desenvolvimento Farmacos & Co, Av Colombo 5790, Bloco B-08, BR-87020900 Maringa, PR - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ARABIAN JOURNAL OF CHEMISTRY; v. 12, n. 8, p. 4006-4016, DEC 2019.
• Citações Web of Science: 1

Resumo

Two 1,5-diaryl-3-oxo-1,4-pentadienyls (1 and 2) having nitro group attached exhibited potent anti-parasitic activity when evaluated against Trypanosoma cruzi and Leishmania amazonensis. In the present work, metabolomic analysis revealed that enzymatic action of T. cruzi reduces the C=C bonds and let the nitro groups intact. Further, these two reduced compounds along with six other congeners were produced by chemical or microbiological methods and evaluated against T. cruzi. All reduced compounds showed less potency than compounds 1 and 2, proving the importance of unsaturated moieties for activity. This investigation provides insight into the mechanism of action of nitro unsaturated diarylpentadienones reinforcing previous studies showing their interference in the redox metabolism of T. cruzi. In the result increase in reactive oxygen and nitrogen species occurs, altering mitochondrial function and depleting the whole antioxidant system, which ultimately causes parasite death. Docking studies using trypanothione oxy-reductase as target helped understanding the activities. The present investigation confirms that enzymes play a pivotal role in drug activation. (C) 2016 The Authors. Published by Elsevier B.V. on behalf of King Saud University. (AU)

• Processo FAPESP: 10/11384-6 - Biotransformação de produtos naturais e sintéticos utilizando micro-organismos endofíticos, uma abordagem quimio-ecológica para a produção de substâncias bioativas
• Beneficiário: Edson Rodrigues Filho
• Modalidade de apoio: Auxílio à Pesquisa - Regular