Abstract
Lack of new anti-cancer and anti-infective agents directed the pharmaceutical research to natural products' discovery especially from actinomycetes as one of the major sources of bioactive compounds. Metabolomics- and dereplication-guided approach has been used successfully in chemical profiling of bioactive actinomycetes. We aimed to study the metabolomic profile of five bioactive actinomycetes to investigate the interesting metabolites responsible for their antimicrobial and anti-cancer activities. Three actinomycetes, namely, Streptomyces sp. SH8, SH10 and SH13, were found to exhibit broad spectrum of antimicrobial activities, whereas isolate SH4 showed the broadest antimicrobial activity against all tested strains. In addition, isolates SH8, SH10 and SH12 displayed potent cytotoxicity against the breast cancer cell line Michigan Cancer Foundation-7 (MCF-7), whereas isolates SH4 and SH12 exhibited potent anti-cancer activity against the hepatoma cell line hepatoma G2 (HepG2) compared with their weak inhibitory properties on the normal breast cells MCF-10A and normal liver cells transformed human liver epithelial-2 (THLE2), respectively. All bioactive isolates were molecularly identified as Streptomyces sp. via 16S rRNA gene sequencing. Our actinobacterial dereplication analysis revealed putative identification of several bioactive metabolites including tetracycline, oxytetracycline and a macrolide antibiotic, novamethymycin. Together, chemical profiling of bioactive Streptomycetes via dereplication and metabolomics helped in assigning their unique metabolites and predicting the bioactive compounds instigating their diverse bioactivities.
Highlights
Various natural product sources have significantly contributed to medication discovery and development especially in the treatment of different cancers and infections [1,2]
It is noteworthy that isolate SH4 exhibited the broadest spectrum of antimicrobial activity against all the indicator strains tested
The current study highlights the importance of combining dereplication and metabolomics data analysis, including the use of supervised and unsupervised multivariate data analysis (MVA), when chemically profiling Streptomycetes for isolate prioritization and chemical isolation
Summary
Various natural product sources have significantly contributed to medication discovery and development especially in the treatment of different cancers and infections [1,2]. More than 40% of the drugs approved as anti-infective or anti-cancer agents in the period from 1981 to 2014 were based on either natural products or their derivatives [2]. The number of reports of antibiotic-resistant microorganisms in both community and clinical settings is growing with increasing rate of mortality. This increase in number of multi-drug resistant pathogens is the main challenge researchers facing to discover new antimicrobial agents with efficacy against those organisms [3]. There is an increasing interest in discovering new natural products to combat the antibiotic resistance [4]
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