title: Cytotoxicity and topo I targeting activity of substituted 10--nitrogenous heterocyclic aromatic group derivatives of SN-38.
abstract: A series of 10-position substituted nitrogenous heterocyclic aromatic group derivatives of SN-38 were prepared. Most of these compounds possessed lower cytotoxicities than CPT. Compound 13 revealed potent cytotoxicity similar to CPT, and compounds 17, 18, and 19 showed similar cytotoxic activity to topotecan. All of the pyridine salt derivatives (7-16) revealed comparable or superior topo I inhibitory activity in relation to CPT. Ethyl in the 7-position of these compounds can increase the cytotoxicity and inhibitory activity to topo I compared with corresponding pyridine salts CPT derivatives (7a-13a) and simultaneously maintain good water solubility. This result is consistent with the SAR of CPT.
authors.affiliation: Key Laboratory of Forest Plant Ecology (Northeast Forestry University), Ministry of Education, 332# No26 Hexing Road, Harbin city, Heilongjiang Province 150040, PR China. li_qingyong@126.com
authors.forename: Qing-Yong
authors.initials: QY
authors.lastname: Li
authors.forename: Xiao-Qiu
authors.initials: XQ
authors.lastname: Deng
authors.forename: Yuan-Gang
authors.initials: YG
authors.lastname: Zu
authors.forename: Hongyan
authors.initials: H
authors.lastname: Lv
authors.forename: Lin
authors.initials: L
authors.lastname: Su
authors.forename: Liping
authors.initials: L
authors.lastname: Yao
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D000077146:Irinotecan; D009584:Nitrogen / Q000737:chemistry*; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D014867:Water; D000077146:Irinotecan; D004264:DNA Topoisomerases, Type I; D009584:Nitrogen; D002166:Camptothecin