New Borrelidins from Onchidium sp. Associated Streptomyces olivaceus SCSIO LO13

Abstract

Borrelidins MÀ O (1 -3), along with four previously known family members (4 -7), were isolated from marine pulmonated mollusks Onchidium sp. associated Streptomyces olivaceus SCSIO LO13. The structures of 1-3 were elucidated by extensive spectral analyses of HR-ESI-MS, 1D and 2D NMR data. In addition, the cytotoxic and antibacterial activities of 1-7 were evaluated enabling us to propose some tentative structure-activity relationships (SARs), especially those involving modifications at C(22) and the moieties at C(7) and C(8) of the borrelidin scaffold.

Bacterial pathogens: threat or treat (a review on bioactive natural products from bacterial pathogens)

“…2 and Table S1 †). [91][92][93][94] Borrelidin 1 features an 18-membered macrolide with a nitrile functionality. 95,96 To date, numerous analogues have been discovered including borrelidins B-O, 87,90,91,93,94 acetyl-borrelidin 89 as well as amide containing congeners, borrelidin CR1 and CR2.…”

“…[91][92][93][94] Borrelidin 1 features an 18-membered macrolide with a nitrile functionality. 95,96 To date, numerous analogues have been discovered including borrelidins B-O, 87,90,91,93,94 acetyl-borrelidin 89 as well as amide containing congeners, borrelidin CR1 and CR2. 92,93,97 More than 30 nitrile-containing pharmaceuticals are currently marketed for a wide range of medical indications, including vildagliptin for diabetes and anastrozole for breast cancer treatment.…”

“…95,96 To date, numerous analogues have been discovered including borrelidins B-O, 87,90,91,93,94 acetyl-borrelidin 89 as well as amide containing congeners, borrelidin CR1 and CR2. 92,93,97 More than 30 nitrile-containing pharmaceuticals are currently marketed for a wide range of medical indications, including vildagliptin for diabetes and anastrozole for breast cancer treatment. 98 The nitrile functionality renders the molecule more water-soluble and less susceptible to oxidative metabolism in the liver.…”

“…100 Borrelidin 1 is active against a wide range of bacteria, including Enterococcus faecalis, Micrococcus luteus, Enterococcus faecium, Proteus hauseri, and Klebsiella pneumoniae (MIC ¼ 0.5-65 mM). 90,91,93 Additionally, borrelidin exhibits 3Â potent activity against Salmonella enterica (MIC ¼ 0.51 mM), the causative agent of foodborne salmonellosis than the antibiotic ampicillin (MIC ¼ 1.4 mM). 91 This remarkable activity has received considerable clinical interest in the search for privileged scaffolds that selectively target S. enterica.…”

“…SAR investigation of the borrelidin scaffold has indicated that the vinylic nitrile and the carboxylic acid moieties are essential for the activity. 87,90,93,94,101 4.1.2 Clostrubins. Clostrubin A 5 was rst isolated as a deep purple pigment from the strictly anaerobic bacterium, Clostridium beijerinckii (HKI0724) in 2014 ( Fig.…”