Isolation, synthesis and bioactivity studies of phomactin terpenoids

Autor(es):Mostrar menos -

Kuroda, Yusuke ^[1] ; Nicacio, Karen J. ^[2] ; da Silva-, Jr., Ildefonso Alves ^[3] ; Leger, Paul R. ^[1] ; Chang, Stanley ^[1] ; Gubiani, Juliana R. ^[2] ; Deflon, Victor M. ^[2] ; Nagashima, Nozomu ^[1] ; Rode, Alexander ^[1] ; Blackford, Katherine ^[1] ; Ferreira, Antonio G. ^[4] ; Sette, Lara D. ^[5] ; Williams, David E. ^{[6, 7]} ; Andersen, Raymond J. ^{[6, 7]} ; Jancar, Sonia ^[3] ; Berlinck, Roberto G. S. ^[2] ; Sarpong, Richmond ^[1]

Afiliação do(s) autor(es)

^[1] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 - USA

^[2] Univ Sao Paulo, Inst Quim Sao Carlos, Sao Carlos, SP - Brazil

^[3] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, Sao Paulo, SP - Brazil

^[4] Univ Fed Sao Carlos, Dept Quim, Sao Carlos, SP - Brazil

^[5] Univ Estadual Paulista, Inst Biociencias, Dept Bioquim & Microbiol, Campus Rio Claro, Rio Claro, SP - Brazil

^[6] Univ British Columbia, Dept Earth Ocean & Atmospher Sci, Vancouver, BC - Canada

^[7] Univ British Columbia, Dept Chem, Vancouver, BC - Canada

• Tipo de documento: Artigo Científico
• Fonte: NATURE CHEMISTRY; v. 10, n. 9, p. 938-945, SEP 2018.
• Citações Web of Science: 7

Resumo

Studies of secondary metabolites (natural products) that cover their isolation, chemical synthesis and bioactivity investigation present myriad opportunities for discovery. For example, the isolation of novel secondary metabolites can inspire advances in chemical synthesis strategies to achieve their practical preparation for biological evaluation. In the process, chemical synthesis can also provide unambiguous structural characterization of the natural products. Although the isolation, chemical synthesis and bioactivity studies of natural products are mutually beneficial, they are often conducted independently. Here, we demonstrate the benefits of a collaborative study of the phomactins, diterpenoid fungal metabolites that serve as antagonists of the platelet activating factor receptor. Our isolation of novel phomactins has spurred the development of a bioinspired, unified approach that achieves the total syntheses of six congeners. We also demonstrate in vitro the beneficial effects of several phomactins in suppressing the rate of repopulation of tumour cells following gamma radiation therapy. (AU)

• Processo FAPESP: 13/50228-8 - Componentes da biodiversidade, e seus caracteres metabólicos, de ilhas do Brasil - uma abordagem integrada
• Beneficiário: Roberto Gomes de Souza Berlinck
• Linha de fomento: Auxílio à Pesquisa - Programa BIOTA - Temático
• Processo FAPESP: 15/01017-0 - EMU concedido no âmbito do projeto aprovado 2013/50228-8, nome do equipamento: uPLC-HRMS (cromatógrafo líquido de ultra resolução acoplado com espectrômetro de massas de alta resolução)
• Beneficiário: Roberto Gomes de Souza Berlinck
• Linha de fomento: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 17/06014-4 - Novos metabólitos secundários de organismos endofíticos e marinhos inibidores do proteassomo: um alvo validado contra câncer
• Beneficiário: Juliana Regina Gubiani
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado