Mass spectrometric approaches for the identification of anthracycline analogs produced by actinobacteria

Autor(es)

Bauermeister, Anelize ^[1] ; Zucchi, Tiago Domingues ^[2] ; Beraldo Moraes, Luiz Alberto ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim, Mass Spectrometry Appl Nat Prod Lab, BR-14040901 Ribeirao Preto, SP - Brazil

^[2] EMBRAPA Meio Ambiente, Lab Microbiol Ambiental, Rod SP 340 Km 127, 5, Caixa Postal 69, BR-13820000 Jaguariuna - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Mass Spectrometry; v. 51, n. 6, p. 437-445, JUN 2016.
• Citações Web of Science: 3

Resumo

Anthracyclines are a well-known chemical class produced by actinobacteria used effectively in cancer treatment; however, these compounds are usually produced in few amounts because of being toxic against their producers. In this work, we successfully explored the mass spectrometry versatility to detect 18 anthracyclines in microbial crude extract. From collision-induced dissociation and nuclear magnetic resonance spectra, we proposed structures for five new and identified three more anthracyclines already described in the literature, nocardicyclins A and B and nothramicin. One new compound 8 (4-{[}4-(dimethylamino)-5-hydroxy-4,6-dimethyloxan-2-yl]oxy-2,5,7,12-tet rahydroxy-3,10-dimethoxy-2-methyl-3,4-dihydrotetracene-1,6,11-trione) was isolated and had its structure confirmed by H-1 nuclear magnetic resonance. The anthracyclines identified in this work show an interesting aminoglycoside, poorly found in natural products, 3-methyl-rhodosamine and derivatives. This fact encouraged to develop a focused method to identify compounds with aminoglycosides (rhodosamine, m/z 158; 3-methyl-rhodosamine, m/z 172; 4-O-acethyl-3-C-methyl-rhodosamine, m/z 214). This method allowed the detection of four more anthracyclines. This focused method can also be applied in the search of these aminoglycosides in other microbial crude extracts. Additionally, it was observed that nocardicyclin A, nothramicin and compound 8 were able to interact to DNA through a DNA-binding study by mass spectrometry, showing its potential as anticancer drugs. Copyright (c) 2016 John Wiley \& Sons, Ltd. (AU)

• Processo FAPESP: 13/50729-7 - DESI-HP-TLC-Bioautografia: uma nova estratégia para identificação rápida de metabólitos secundários anti-mastítico, produzido por actinobactérias
• Beneficiário: Luiz Alberto Beraldo de Moraes
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Regular