Preparation and Structure-Activity Relationships of Novel Asterriquinone Derivatives

• Published in: Chemical & pharmaceutical bulletin Vol. 46; no. 8; pp. 1325 - 1329
• Main Authors: KAJI, Akira, KIMURA, Kengo, TERANISHI, Masanori, KIRIYAMA, Noriki, NOMURA, Masaaki, MIYAMOTO, Ken-ichi
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 1998; Maruzen; Japan Science and Technology Agency
• Subjects: Antineoplastic agents; asterriquinone; Biological and medical sciences; cytotoxicity; General aspects; Medical sciences; mouse leukemia P388 cell; partial deacetylation; Pharmacology. Drug treatments; structure-activity relationship; Antineoplastic agent; Nitrogen heterocycle; Quinone; Rodentia; P388-Leukemia; Cytotoxicity; In vitro; Vertebrata; Mammalia; Structure activity relation; Mouse; Animal; Bicyclic compound; Benzenic compound; Aromatic compound; Indole derivatives; Chemical synthesis; Tumor cell
• DOI: 10.1248/cpb.46.1325
• EISSN: 1347-5223
• ISSN: 0009-2363

Asterriquinone (ARQ, 1a) is an antitumor metabolite of Aspergillus terreus IFO 6123. To gain insight into the structure-activity relationships of ARQ, a series of chemically modified derivatives (1-6), the ARQ analogues (b-e) and the 2, 5-dihydroxy-p-bezoquinone analogues (f-h), were prepared, and cytotoxic acitivity against mouse leukemia P388 cells investigated. Results indicated that : 1) at least one hydroxy group or acetoxy group in the p-benzoquinone moiety is important to exhibit cytotoxicity; 2) in the p-benzoquinone moiety, a single methoxy group and/or one aceotxy group substitution showed more potent cytotoxicity than when two hydroxy groups are substituted (1); 3) the indole ring is important for the cytotoxicity of ARQ analogues; 4) the 1, 1-dimethly-2-propenyl group in the indole ring is not important for the cytotoxic activity of ARQ.