title: Synthesis of 1-substituted carbazolyl-1,2,3,4-tetrahydro- and carbazolyl-3,4-dihydro-β-carboline analogs as potential antitumor agents.
abstract: A series of 1-substituted carbazolyl-1,2,3,4-tetrahydro- and carbazolyl-3,4-dihydro-β-carboline analogs have been synthesized and evaluated for antitumor activity against human tumor cells including KB, DLD, NCI-H661, Hepa, and HepG2/A2 cell lines. Among these, compounds 2, 6, 7, and 9 exhibited the most potent and selective activity against the tested tumor cells. As for inhibition of topoisomerase II, compounds 1-14 and 18 showed better activity than etoposide. Among them, compounds 3, 4, 7, 9, and 10 exhibited potent activity. The structure and activity relationship (SAR) study revealed correlation between carbon numbers of the side chain and biological activities. The molecular complex with DNA for compound 2 was proposed.
authors.affiliation: School of Pharmacy, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Ya-Ching
authors.initials: YC
authors.lastname: Shen
authors.affiliation: School of Pharmacy, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Yao-To
authors.initials: YT
authors.lastname: Chang
authors.affiliation: School of Pharmacy, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Chun-Ling
authors.initials: CL
authors.lastname: Lin
authors.affiliation: School of Pharmacy, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Chia-Ching
authors.identifier: 0000-0001-5642-4679
authors.initials: CC
authors.lastname: Liaw
authors.affiliation: National Research Institute of Chinese Medicine, Taipei 112, Taiwan.
authors.forename: Yao Haur
authors.initials: YH
authors.lastname: Kuo
authors.affiliation: Institute of Biochemistry, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Lan-Chun
authors.initials: LC
authors.lastname: Tu
authors.affiliation: Institute of Biochemistry, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Sheau Farn
authors.initials: SF
authors.lastname: Yeh
authors.affiliation: School of Pharmacy, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Ji-Wang
authors.initials: JW
authors.lastname: Chern
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002227:Carbazoles / Q000737:chemistry*; D002243:Carbolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D007624:KB Cells; D008958:Models, Molecular; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; D002243:Carbolines