Lobophorins A and B, new antiinflammatory macrolides produced by a tropical marine bacterium

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

“…10 Compound 4 was determined to be lobophorin B by comparing 1 H, 13 C, 1 H-1 H COSY and HMBC NMR spectral data with those reported in literature (Table 1). 10 The molecular formula of compound 1 was established as C 61 H 89 N 2 O 20 by HR-MS (m/z 1169.5874 [MÀH] À , calcd 1169.6009). The IR spectrum of 1 showed absorption bands characteristic of hydroxyl (3522 and 3439 cm À1 ), methylene (2932 cm À1 ), carboxyl (1734 cm À1 ) and olefinic groups (1627, 1545 and 1454 cm À1 ).…”

“…The 1 H and 13 C NMR spectra of 1 were almost identical to those of lobophorin B (4). 10 The difference between 1 and 4 is that the oxygenated methylene (d H 4.15 (2H, m, H-32) and d C 64.7 (t, C-32)) in 4 was replaced by a methyl singlet (d H 1.80 (3H, s, Me-32) and d C 21.8 (q, Me-32)) in 1, indicating the absence of C-32-OH in 1 (Table 1). Consistently, the HMBC correlations from proton signals of the methyl singlet H 3 -32 to C-21, C-22 and C-23 confirmed the location of this methyl group at C-32 in 1.…”

“…19 A pair of spirotetranate antibiotics lobophorins A (3) and B (4), previously isolated from an alga-associated acintobacterium, were shown to exhibit anti-inflammatory but no antimicrobial activities. 10 Very recently, two C-8 stereoisomers of 3 and 4, named lobophorins C and D, were isolated from a marine spongerelated Streptomyces strain and were shown to have selective cytotoxicities against different cell lines. 20 Interestingly, our study reveals that the absence of the C-32 hydroxyl group in lobophorins E (1) and F (2), when compared with compound 4 (4128 mg ml À1 ), significantly enhances their antimicrobial properties against S. aureus ATCC 29213: 416-fold improvement with 2 (8 mg ml À1 ).…”

“…Two compounds were identified to be novel lobophorin analogues, designated lobophorins E (1) and F (2), and the other two were found to be lobophorins A (3) and B (4). 10 Interestingly, lobophorin F (2) exhibited better cytotoxic activities against three tumor cell lines (SF-268, MCF-7 and NCI-H460) and better antibacterial activities than lobophorin B (4).…”

Novel Lobophorins Inhibit Oral Cancer Cell Growth and Induce Atf4- and Chop-Dependent Cell Death in Murine Fibroblasts

“…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.…”