Oxidative functionalization of a halimane diterpenoid achieved by fungal transformation

Autor(es)

Monteiro, Afif Felix ^{[1, 2]} ; Righetto, Gabriela Marinho ^[3] ; Simoes, Laura Vilar ^[2] ; de Almeida, Larissa Costa ^[4] ; Costa-Lotufo, Leticia Veras ^[4] ; Baratella da Cunha Camargo, Ilana Lopes ^[3] ; Castro-Gamboa, Ian ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Quim Sao Carlos, CP 780, BR-13560970 Sao Carlos, SP - Brazil

^[2] Univ Estadual Paulista, UNESP, Nucleo Bioensaios Biossintese & Ecofisiol Prod Na, Inst Quim, Dept Quim Orgincia, Francisco Degni 55, BR-14800900 Araraquara, SP - Brazil

^[3] Univ Sao Paulo, Sao Carlos Inst Phys, POB 369, BR-13556097 Sao Carlos, SP - Brazil

^[4] Univ Sao Paulo, Inst CiPncias BiomM, Av Lineu Prestes 1524, BR-05508900 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOORGANIC CHEMISTRY; v. 86, p. 550-556, MAY 2019.
• Citações Web of Science: 0

Resumo

Regio and stereoselective activation of sp(3) C-H bonds remain one of the major advantages of biocatalysis over traditional chemocatalytic methods. Herein, we describe the oxy-functionalization of halimane diterpenoid 1 by whole cells of three filamentous fungi, aiming to obtain derivatives with desirable biological properties. After incubating 1 with Fusarium oxysporum, Myrothecium verrucaria, and Rhinocladiella similis at different concentrations and incubation times, four known (3, 5, 6, and 7) and three new (2, 4, and 8) halimane derivatives were obtained and characterized. F. oxysporum catalyzed the hydroxylation of positions C-2 (2) and C-7 (4), while R. similis simultaneously mediated the 2-oxo-functionalization and the hydration of 13,14-(C-C)double bond belonging to an alpha, beta-unsaturated carbonyl system (8). Compounds 1-7 were non-cytotoxic against HCT-116 and MCF-7 cancer cell lines at tested concentrations. However, substrate 1 displayed moderate reduction ability against biofilm produced by Staphylococcus epidermidis ATCC35984 (84% at 1.6 mM), and this effect was retained to some extent by derivatives 4 and 7. These results emphasize the prominent potential of filamentous fungi associated with the microbiota of medicinal plants as versatile catalysts for singularly useful reactions through their complex enzymatic machinery, as well as the high susceptibility of halimane-diterpenoid substrates. (AU)

• Processo FAPESP: 16/24969-9 - Avaliação de compostos em patógenos bacterianos multirresistentes como parte do Centro de Pesquisa e Inovação em Biodiversidade e Fármacos - CIBFar
• Beneficiário: Gabriela Marinho Righetto
• Linha de fomento: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos
• Beneficiário: Glaucius Oliva
• Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs