Bioactive 2(1H)-Pyrazinones and Diketopiperazine Alkaloids from a Tunicate-Derived Actinomycete Streptomyces sp.

Abstract

As a part of our ongoing effort to allocate marine microbial bioactive leads, a tunicate-derived actinomycete, Streptomyces sp. Did-27, was investigated. Three new 2(1H)-pyrazinones derivatives, (2) and (S)-6-(sec-butyl)-3-isobutylpyrazin-2(1H)-one (3), together with the known (1H)-pyrazinones analogues deoxymutaaspergillic acid (4), 3,6-diisobutyl-2(1H)-pyrazinone (5) and 3,6-di-sec-butyl-2(1H)-pyrazinone (6), and the diketopiperazine alkaloids cyclo(6-OH-D-Pro-L-Phe) (7), bacillusamide B (8), cyclo(L-Pro-L-Leu) and cyclo(L-Pro-L-Ile) (10) were isolated from this strain. The structures of the compounds were determined by study of their one-and two-dimensional NMR spectra as well as high-resolution mass spectral determinations. Compound 4 was reported previously as a synthetic product, while compound 6 was reported as 2-hydroxy-3,6-di-sec-butylpyrazine. Herein, we report the complete NMR data for compounds 4 and 6. The compounds were evaluated for their cytotoxic activities against three cell lines. Compound 5 showed potent and selective activity against HCT-116 cell line with IC 50 of 1.5 µg/mL, while 1-10 showed variable cytotoxic activities against these cancer cell lines. These results provide further understanding about the chemistry and bioactivities of the alkylated 2(1H)-pyrazinone derivatives.

Natural Products Repertoire of the Red Sea

“…Did-27, collected from a location near Obhur, Saudi Arabia ( Figure 6). The alkaloid 15 displayed selective cytotoxicity against HCT-116 cell line with IC 50 value of 1.5 µg/mL [52]. The four bioactive metabolites chrysophanol 8-methyl ether (16), asphodelin (17), justicidin B (18) and ayamycin (19) were isolated from the actinomycete Nocardia sp.…”

“…In 1993, a bioassay-guided fractionation of an organic extract of the sponge Toxiclona toxius yielded the hexaprenoid hydroquinones toxiusol (50), shaagrockol C (51), toxicol A (52) and toxicol B (53) ( Figure 11) [73]. In the same year, another study published the isolation of toxiusol (50), toxicol A (52) and toxicol B (53) form the marine sponge Toxiclona toxius [74]. One year earlier, shaagrockol C (51) was also identified and isolated from the sponge Toxiclona toxius [75].…”

Biological and Chemical Diversity of Ascidian-Associated Microorganisms

“…Did-27, which is associated with the Didemnum sp. These compounds exhibited cytotoxic activities against cancer cell lines HCT-116, HepG2 and MCF-7 [ 62 ]. Three new 2(1 H )-pyrazinone derivatives, including ( S )-6-(sec-butyl)-3-isopropylpyrazin-2(1 H )-one ( 90 ), ( S )-3-(sec-butyl)-6-isopropylpyrazin-2(1 H )-one ( 91 ) and ( S )-6-(sec-butyl)-3-isobutylpyrazin-2(1 H )-one ( 92 ), together with the known (1 H )-pyrazinones analogues deoxymutaaspergillic acid ( 93 ), 3,6-diisobutyl-2(1 H )-pyrazinone ( 94 ) and 3,6-disec-butyl-2(1 H )-pyrazinone ( 95 ) were isolated from the actinobacteria Streptomyces sp., which is associated with Didemnum sp.…”

“…Three new 2(1 H )-pyrazinone derivatives, including ( S )-6-(sec-butyl)-3-isopropylpyrazin-2(1 H )-one ( 90 ), ( S )-3-(sec-butyl)-6-isopropylpyrazin-2(1 H )-one ( 91 ) and ( S )-6-(sec-butyl)-3-isobutylpyrazin-2(1 H )-one ( 92 ), together with the known (1 H )-pyrazinones analogues deoxymutaaspergillic acid ( 93 ), 3,6-diisobutyl-2(1 H )-pyrazinone ( 94 ) and 3,6-disec-butyl-2(1 H )-pyrazinone ( 95 ) were isolated from the actinobacteria Streptomyces sp., which is associated with Didemnum sp. Expect for compound 91 , all the other compounds presented cytotoxic activities against cancer cell lines HCT-116, HepG2 and MCF-7 [ 62 ].…”

Cytotoxic and Antimicrobial Compounds from the Marine-Derived Fungus, Penicillium Species

“…Our growing interest in identifying secondary metabolites from marine microbes resulted in the identification of several compounds with different bioactivities [ 13 , 14 , 15 , 16 , 17 ]. The organic extract of the fungus Penicillium sp.…”