title: NAD(P)H quinone oxidoreductase 1 (NQO1)-bioactivated pronqodine A regulates prostaglandin release from human synovial sarcoma cells.
abstract: Natural products have contributed to the elucidation of biological mechanisms as well as drug discovery research. Even now, the expectation for natural products is undiminished. We screened prostaglandin release inhibitors that had no effect on in vitro cyclooxygenase activity derived from natural product sources and discovered pronqodine A. Using spectral analysis and total synthesis, the structure of pronqodine A was shown to be a benzo[d]isothiazole-4,7-dione analogue. Evaluation of the biological activity of pronqodine A revealed that the NAD(P)H dehydrogenase quinone 1 (NQO1) converted pronqodine A into a two-electron reductive form. The reductive form underwent autoxidation and reversed to its native form immediately with the generation of reactive oxygen species. Further investigations proved that pronqodine A inhibited cyclooxygenase enzyme activity only in the presence of NQO1. Pronqodine A acts as a potential bioreductive compound, inhibiting prostaglandin release in selectively activated NQO1-expressing cells.
authors: Institute of Microbial Chemistry (BIKAKEN), 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan. nakaek@bikaken.or.jp
authors: Koichi
authors: K
authors: Nakae
authors: Hayamitsu
authors: H
authors: Adachi
authors: Ryuichi
authors: R
authors: Sawa
authors: Nobuo
authors: N
authors: Hosokawa
authors: Masaki
authors: M
authors: Hatano
authors: Masayuki
authors: M
authors: Igarashi
authors: Yoshio
authors: Y
authors: Nishimura
authors: Yuzuru
authors: Y
authors: Akamatsu
authors: Akio
authors: A
authors: Nomoto
mesh_terms: D016227:Benzoquinones / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D010084:Oxidation-Reduction; D011453:Prostaglandins / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species; D013584:Sarcoma, Synovial / Q000378:metabolism; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D016227:Benzoquinones; D011453:Prostaglandins; D017382:Reactive Oxygen Species; D013844:Thiazoles; C582580:pronqodine A; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human