Marinocyanins, cytotoxic bromo-phenazinone meroterpenoids from a marine bacterium from the streptomycete clade MAR4

Abstract

Six cytotoxic and antimicrobial metabolites of a new bromo-phenazinone class, the marinocyanins A-F (1–6), were isolated together with the known bacterial metabolites 2-bromo-1-hydroxyphenazine (7), lavanducyanin (8, WS-9659A) and its chlorinated analog WS-9659B (9). These metabolites were purified by bioassay-guided fractionation of the extracts of our MAR4 marine actinomycete strains CNS-284 and CNY-960. The structures of the new compounds were determined by detailed spectroscopic methods and marinocyanin A (1) was confirmed by crystallographic methods. The marinocyanins represent the first bromo-phenazinones with an N-isoprenoid substituent in the skeleton. Marinocyanins A-F show strong to weak cytotoxicity against HCT-116 human colon carcinoma and possess modest antimicrobial activities against Staphylococcus aureus and amphotericin-resistant Candida albicans.

Anti-Diabetic Activity of 2,3,6-Tribromo-4,5-Dihydroxybenzyl Derivatives from Symphyocladia latiuscula through PTP1B Downregulation and α-Glucosidase Inhibition

“…In response to various ecological pressures, marine organisms such as algae, sponges, and corals produce a wide range of biologically active secondary metabolites, 45% of which are brome-metabolites due to the high bromine concentration in sea water [8,9]. Natural brominated compounds have been reported to exhibit a variety of biological activities including antibacterial, antifungal, antiviral, antioxidant, antitumor, anti-inflammatory, and enzymatic activity through protein kinase and acetyl-cholinesterase inhibition [10,11,12,13]. Secondary metabolites from marine sources have been regarded as an invaluable source of therapeutic agents, and these metabolites have been subsequently modified via semi-synthetic routes to enhance their therapeutic effects.…”

Structural and Mechanistic Insight into Terpene Synthases that Catalyze the Irregular Non‐Head‐to‐Tail Coupling of Prenyl Substrates

“…However, little is known about the biosynthesis of such natural products, and the enzyme, namely, prenyltransferase, responsible for attaching the cyclolavandulyl group remains uncharacterized. Attachment of the cyclolavandulyl group produces a relatively large change in the chemical and biological properties . Some kinds of prenyltransferases often exhibit promiscuity to prenyl acceptors .…”

“…Attachment of the cyclolavandulyl group produces ar elativelyl arge change in the chemical and biological properties. [17] Some kinds of prenyltransferases often exhibit promiscuityt op renyl acceptors. [18,19] Thus,i dentification and characterization of the prenyltransferase for the cyclolavandulyl group should guide the design of modified enzymes that can be used to alter the biological activity of naturalp roducts.…”

Synthesis and Cytotoxic Evaluation of N-Alkyl-2-halophenazin-1-ones

“…and actinomycete strains CNS-284 and CNY-960. 15 , 19 Compounds 2b and 3b inhibited TNF-α-induced NFκB activity (IC 50 values of 4.1 and 24.2 μM, respectively) and LPS-induced nitric oxide production (IC 50 values of >48.6 and 15.1 μM, respectively). 15 They blocked PGE 2 production with greater efficacy (IC 50 values of 7.5 and 0.89 μM, respectively).…”

“… 19 In addition, both these compounds display modest antimicrobial activity against Staphylococcus aureus and the pathogenic yeast Candida albicans . 19 …”