Lobophorins E and F, new spirotetronate antibiotics from a South China Sea-derived Streptomyces sp. SCSIO 01127

Abstract

The strain SCSIO 01127, isolated from the South China Sea sediment, was identified as a member of Streptomyces by the 16S rDNA sequence analysis. Two new spirotetronate antibiotics lobophorins E (1) and F (2), along with two known analogs lobophorins A (3) and B (4), were isolated from Streptomyces sp. SCSIO 01127. Their structures were elucidated on the basis of detailed IR, NMR and MS spectroscopic analyses. The new compound lobophorin F (2) showed antibacterial activities against Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 with MIC values of 8 mg ml À1 for both the strains, better than that of lobophorin B (4). Lobophorin F (2) also displayed better cytotoxic activities than lobophorin B (4), with IC 50 of 6.82, 2.93 and 3.16 mM against SF-268, MCF-7 and NCI-H460, respectively.

Recent advances in the field of bioactive tetronates

“…SCSIO 01127 isolate from the South China Sea sediment. 99 In 2013, lobophorin G along with the known compounds A and B was isolated from Streptomyces sp. MS100061 (soil sample from the South China Sea).…”

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“…Lobophorins E, F, and CR1−3 were identified in a DMSO extract that could significantly activate a Chop-luciferase reporter but not an XBP1-luciferase reporter ( Figure S1), suggesting that one or more compounds could selectively activate the apoptotic arm of the UPR. Bioassay guided fractionation of extracts prepared from the active strain 7790_N4 allowed for the isolation of the spirotetronate macrolides lobophorin A, B, E, and F (1−4) 12,13 and three new congeners designated CR1 (5), CR2 (6), and CR3 (7) (Figure 2). Lobophorin CR1 (5) 4) showing the same shifts as 1 appeared a new quaternary carbon at δ C 71.5 instead of at δ C 52.4 or 91.0 as in lobophorin A (1) and B (2), respectively.…”

“…These data enabled us to propose the structure of CR2 (see Figure 2), which was supported by a key ROESY cross peak between H-30a (δ H 4.78) and H 2 -16 (δ H16a 1.80 and δ H16b 1.91) (Table S2 and Figures S8−S12). Insufficient CR2 was isolated to obtain reliable 13 C NMR. Lobophorin CR3 (7) 13 C NMR shifts of 7 with those present in 6, only one difference was observed.…”

“…Insufficient CR2 was isolated to obtain reliable 13 C NMR. Lobophorin CR3 (7) 13 C NMR shifts of 7 with those present in 6, only one difference was observed. Carbon C-15 shifted downfield from δ C 67.9 to δ C 81.0, which can only be explained by the presence of a hydroperoxyl group at C-15 instead of the hydroxyl (Figure 2 and Table S3 and Figures S13−S18).…”

“…Experimental procedures for cell culture and reagents, proliferation, and polymerase chain reaction, 13 C and 1 H NMR data for lobophorins CR1−CR3, 1 H NMR spectra of lobophorins CR1−CR3, 13 C NMR spectra of lobophorins CR1−CR3, COSY spectra of lobophorins CR1−CR3, HSQC spectra of lobophorins CR1−CR3, HMBC spectra of lobophorins CR1−CR3, and ROESY spectra of lobophorins CR1−CR3. The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/ acsmedchemlett.5b00127.…”