title: 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, (S)-6-(sec-butyl)-3-isopropylpyrazin-2(1H)-one (1), (S)-3-(sec-butyl)-6-isopropylpyrazin-2(1H)-one (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 IC50 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.
authors: Natural Products Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia. lshalla@kau.edu.sa.|Suez Canal University Hospital, Suez Canal University, Ismailia 41522, Egypt. lshalla@kau.edu.sa.
authors: Lamiaa A
authors: LA
authors: Shaala
authors: Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia. dyoussef@kau.edu.sa.
authors: Diaa T A
authors: DT
authors: Youssef
authors: Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia. jibrahim@kau.edu.sa.|Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt. jibrahim@kau.edu.sa.
authors: Jihan M
authors: JM
authors: Badr
authors: Special Infectious Agents Unit, Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia. sharakeh@gmail.com.
authors: Steve M
authors: SM
authors: Harakeh
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D054659:Diketopiperazines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D011719:Pyrazines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013302:Streptomyces / Q000737:chemistry* / Q000254:growth & development / Q000302:isolation & purification; D014561:Urochordata / Q000382:microbiology*
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D054659:Diketopiperazines; D011719:Pyrazines
keywords: Red Sea Didemnum sp.; Streptomyces sp. Did-27; alkylated 2(1H)-pyrazinone derivatives; antiproliferative and cytotoxic activities; cancer cell lines; diketopiperazine alkaloids