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

Abstract

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.

Microorganisms as Alternative Sources of New Natural Products

“…Another interesting example of antitumoral compounds is an already known compound that is widely used for breast cancer stage III and IV treatment, which is doxorubicin [71], isolated from a mutant strain of Streptomyces peuceticus. Doxorubicin works as a DNA intercalating agent by inhibiting the activity of topoisomerase II in DNA replication [72].…”

Antimicrobial activity of crude extracts from actinomycetes against mastitis pathogens

“…To obtain crude extracts, actinomycetes named Caat 1-54 and Caat P5-8 were cultivated in 500-mL Erlenmeyer flasks containing 100 mL of potato dextrose medium at 30°C under shaking conditions at 150 rpm for 10 d. Both crude extracts, Caat 1-54 and Caat P5-8, were submitted to the same purification process. The isolate Caat 1-54 was inoculated in 4.5 L of yeast extract-malt extract medium (ISP2) and, after 10 d, the broth fermentation was submitted to liquidliquid extraction with ethyl acetate (Bauermeister et al, 2016). A total of 240 mg of crude extract was puri-fied using a preparative LC with UV detection with a binary pump (Shimadzu Corp., Kyoto, Japan).…”

Natural products in green-detection of cancer cells, cancer therapy, and monitoring of therapeutic and cancer progression: A perspective

“…Moreover, the anthracyclines produced by actinobacteria are used effectively in the treatment of cancer, can be detected their levels in biological samples by using spectroscopic methods such as mass spectrometry. It should be mentioned that, the anthracyclines are toxic to their producers (Bauermeister et al 2016). Thus, the detection of these drugs may be an application of controlling and monitoring the levels of anticancer drugs in surrounding normal cells.…”