New Capoamycin-Type Antibiotics and Polyene Acids from Marine Streptomyces fradiae PTZ0025

Abstract

Capoamycin-type antibiotics (2–5) and polyene acids (6, 7) were isolated from marine Streptomyces fradiae strain PTZ0025. Their structures were established by extensive nuclear magnetic resonance (NMR) and high resolution electron spray ionization mass spectroscopy (HRESIMS) analyses and chemical degradation. Compounds 3, 4, 6, 7 were found to be new and named as fradimycins A (3) and B (4), and fradic acids A (6) and B (7). Compounds 3–5 showed in vitro antimicrobial activity against Staphylococcus aureus with a minimal inhibitory concentration (MIC) of 2.0 to 6.0 μg/mL. Interestingly, Compounds 3–5 also significantly inhibited cell growth of colon cancer and glioma with IC50 values ranging from 0.13 to 6.46 μM. Fradimycin B (4), the most active compound, was further determined to arrest cell cycle and induce apoptosis in tumor cells. The results indicated that fradimycin B (4) arrested the cell cycle at the G0/G1 phase and induced apoptosis and necrosis in colon cancer and glioma cells. Taken together, the results demonstrated that the marine natural products 3–5, particularly fradimycin B (4), possessed potent antimicrobial and antitumor activities.

A new curvularin glycoside and its cytotoxic and antibacterial analogues from marine actinomycete Pseudonocardia sp. HS7

“…The aglycone and curvularin (5) had a same HPLC retention time and very close negative optical rotation values, suggesting that both compounds had a same configuration at C-15 (Dai et al 2010;Lai et al 1989). Therefore, the aglycone of 3 was proved to be curvularin (5). Further comparison of the NMR data of 3 with those of 3a included that the structural difference between 3 and 3a was their sugar part.…”

“…The activity of compounds 1 -5 and 5a-5c inhibiting the proliferation of six cell lines of glioma C6, U87-MG, SHG-44, U251 and colorectal cancer HCT-15 and SW620 was determined by Sulforhodamine B (SRB) assay (Xin et al 2012;Yu, Ye, Chen et al 2014;Yu et al 2015;Yu, Ye, Xin et al 2014). Doxorubicin (DOX, one of the most potent of the chemotherapeutic drugs) (Tacara et al 2013) was used as positive control.…”

“…There is therefore a need to discover lead compounds for the development of novel anti-glioma drugs. Natural products are highly significant sources of new drug leads (Newman & Cragg 2012 During the course of our ongoing programme for the discovery of novel anti-glioma agents from natural sources (Xin et al 2012;Ye et al 2014;Yu, Ye, Chen et al 2014;Yu et al 2015;Yu, Ye, Xin et al 2014), the cultured broth of marine actinomycete strain HS7 isolated from the cloacal aperture of sea cucumber Holothuria moebii was found to be active against the proliferation of glioma cells. The strain HS7 was identified by 16S rDNA sequence analysis and its top16S rDNA sequence was 100% sequence match to Pseudonocardia antitumoralis strain SCSIO 01299.…”

Nuclear Magnetic Resonance Spectroscopy for Structural Characterization of Bioactive Compounds

“…The correlations observed for both H-12 and 13-CH 2 with H-2, indicated a cis-orientation for H-2 H-12, and C-13, and assigns the (2S*, 3R*, 12R*)-configuration of tryptoquivaline K 29 [31]. The relative stereochemistry of the two heterocyclic rings of the antibacterial and antitumor agent fradimycin A 30 was based on the ROESY correlations of H-1Ј with H-5Ј, H-4Ј with H-6Ј, H-7ЈЈ with H-9ЈЈ, H-8ЈЈ with H-10ЈЈ and H-9ЈЈ with H-13ЈЈ [32]. The (E)-geometry of the two double bonds at C-12 and C-16 of the antibacterial and antitumor agent napyradiomycin A 31 was determined by the ROESY correlations between H-11 with H-12 and 13-CH3-Me and the absence of correlation between H-12 and 13-CH3-Me and also between H-19 with H-16, respectively [33].…”

New Metabolites and Bioactive Actinomycins from Marine-Derived Streptomyces sp. ZZ338

“…During the course of our ongoing project to discover novel antiglioma agents from marine sources [10,11,12,13,14,15], a marine-derived actinomycete strain, ZZ338, was isolated from sea squirts grown on coastal rocks. A crude extract prepared from the culture of this isolated strain ZZ338 in Gause’s liquid medium showed antimicrobial and antiproliferative activities.…”