title: Chemistry of Renieramycins. 15. Synthesis of 22-O-Ester Derivatives of Jorunnamycin A and Their Cytotoxicity against Non-Small-Cell Lung Cancer Cells.
abstract: Eighteen 22-O-ester derivatives of jorunnamycin A (2) were prepared via 2, and their cytotoxicity against human non-small-cell lung cancer (NSCLC) cells was evaluated. Preliminary study of the structure-cytotoxicity relationship revealed that the ester part containing a nitrogen-heterocyclic ring elevated the cytotoxicity of the 22-O-ester derivatives. Among them, 22-O-(4-pyridinecarbonyl) ester 6a is the most potent compound (IC50 1.1 and 1.6 nM), exhibiting 21-fold and 5-fold increases in cytotoxicity against the H292 and H460 NSCLC cell lines, respectively, relative to renieramycin M (1), the major cytotoxic bistetrahydroisoquinolinequinone alkaloid of the Thai blue sponge Xestospongia sp.
authors.forename: Natchanun
authors.initials: N
authors.lastname: Sirimangkalakitti
authors.forename: Supakarn
authors.initials: S
authors.lastname: Chamni
authors.affiliation: Bureau of Drug and Narcotic, Department of Medical Sciences, Ministry of Public Health , Nonthaburi 11000, Thailand.
authors.forename: Kornvika
authors.initials: K
authors.lastname: Charupant
authors.forename: Pithi
authors.initials: P
authors.lastname: Chanvorachote
authors.affiliation: Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University , 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
authors.forename: Nanae
authors.initials: N
authors.lastname: Mori
authors.affiliation: Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University , 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Saito
authors.forename: Khanit
authors.initials: K
authors.lastname: Suwanborirux
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008386:Marine Biology; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013785:Thailand
chemical_list: D000970:Antineoplastic Agents; D007546:Isoquinolines; D015363:Quinolones; D044005:Tetrahydroisoquinolines; C584995:jorunnamycin A; C482478:renieramycin M; D002945:Cisplatin