Mass spectrometric approaches for the identification of anthracycline analogs produced by actinobacteria.
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-tetrahydroxy-3,10-dimethoxy-2-methyl-3,4-dihydrotetracene-1,6,11-trione) was isolated and had its structure confirmed by (1) H 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 © 2016 John Wiley & Sons, Ltd.
Mass Spectrometry Applied to Natural Products Laboratory, Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, CEP: 14040-901, Ribeirão Preto, SP, Brazil.
Anelize
A
Bauermeister
Laboratório de Microbiologia Ambiental, Rod SP 340-Km 127, 5, Caixa Postal 69, EMBRAPA Meio Ambiente, 13820-000, Jaguariúna, Brazil.
Tiago Domingues
TD
Zucchi
Mass Spectrometry Applied to Natural Products Laboratory, Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, CEP: 14040-901, Ribeirão Preto, SP, Brazil.
Luiz Alberto Beraldo
LA
Moraes
D039903:Actinobacteria / Q000737:chemistry*; D018943:Anthracyclines / Q000032:analysis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000032:analysis* / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods*
D018943:Anthracyclines; D000970:Antineoplastic Agents; C109702:nocardicyclin A; C109703:nocardicyclin B; C111762:nothramicin; D004247:DNA
actinobacteria; cancer; natural products; nocardicyclin; nothramicin; precursor ion