Monacyclinones, New Angucyclinone Metabolites Isolated from Streptomyces sp. M7_15 Associated with the Puerto Rican Sponge Scopalina ruetzleri

Abstract

During an investigation of new actinomycete species from Caribbean sponges for novel bioactive natural products, frigocyclinone (1), dimethyldehydrorabelomycin (3) and six new angucyclinone derivatives were isolated from Streptomyces sp. strain M7_15 associated with the sponge Scopalina ruetzleri. Of these, monacyclinones A–B (4–5) contain the core ring structure of dehydrorabelomycin (2) with the aminodeoxysugar found in frigocyclinone (1). Monacyclinone C (6) is a hydroxylated variant of frigocyclinone (1) and monacyclinone D (7) is a Baeyer Villiger derivative of (6) which also exists as the open chain hydrolysis product monacyclinone E (8). Monacyclinone F (9) contains two unique epoxide rings attached to the angucyclinone moiety and an additional aminodeoxysugar attached through an angular oxygen bond. All structures were confirmed through spectral analyses. Activity against rhabdomycosarcoma cancer cells (SJCRH30) after 48 h of treatment was observed with frigocyclinone (1; EC50 = 5.2 µM), monacyclinone C (6; 160 µM), monacyclinone E (8; 270 µM), and monacyclinone F (9; 0.73 µM). The strongest bioactivity against rhabdomycosarcoma cancer cells and gram-positive bacteria was exhibited by compound 9, suggesting that the extra aminodeoxysugar subunit is important for biological activity.

Microorganisms Associated with the Marine Sponge Scopalina hapalia: A Reservoir of Bioactive Molecules to Slow Down the Aging Process

“…Surprisingly, few bioactive compounds were reported from Scopalina spp. In 2015, Vicente and co-workers reported the isolation of six new angucyclinone (aromatic polyketide) derivatives from a Streptomyces strain associated with S. ruetzleri [ 102 ]. Monacyclinone C ( 7 ) and E ( 8 ) exhibited moderate cytotoxic activities against rhabdomyosarcoma cancer cells, while monacyclinone F ( 9 ) showed the highest cytotoxic activity along with antibacterial property ( Figure 6 ).…”

Isolation, stereochemical study, and racemization of (±)‐pratenone A, the first naturally occurring 3‐(1‐naphthyl)‐2‐benzofuran‐1(3H)‐one polyketide from a marine‐derived actinobacterium

“…Angucyclinones, aromatic polyketides isolated exclusively from actinomycetes, have drawn much attention for their broad biological activities, mainly as antibacterial and anticancer agents . Since the first member tetrangomycin reported in 1965, the angucyclinone family has steadily increased, and more than 200 members have been described to date . Most representatives of this family feature a characteristic tetracyclic benz[ a ]anthracene topology, and less than 20 of them possess ring C‐modified skeleton .…”

“…1 Since the first member tetrangomycin reported in 1965, the angucyclinone family has steadily increased, and more than 200 members have been described to date. [2][3][4][5][6][7][8] Most representatives of this family feature a characteristic tetracyclic benz[a]anthracene topology, and less than 20 of them possess ring C-modified skeleton. [9][10][11] It is striking to see that ring C-modification often generates intriguing chemical scaffolds, for instance, C-ring expansion and cleavage give rise to emycins D−F with unprecedented molecular frameworks plausibly modified by an enzymatic Baeyer-Villiger oxidation from the angucyclinone precursor ochromycinone.…”

Four newScopalinafrom Southern California: the first Scopalinida (Porifera: Demospongiae) from the temperate Eastern Pacific

“…Little has been published on the biology of these genera, though advances have been made on the population genetics and symbiont relationships in several species (Blanquer & Uriz 2008Lee et al 2009;Souza et al 2017). Some Scopalinida have also been found to be sources for novel anti-microbial or anti-tumor compounds, which further motivates efforts to characterize their diversity (Avilés et al 2013;Vicente et al 2015;Wei et al 2007).…”