title: Synthesis, in vitro antitumor evaluation and DNA-binding study of novel tetrahydroquinolines and some derived tricyclic and tetracyclic ring systems.
abstract: The synthesis of some new tetrahydroquinolines, tetrahydropyrimido[4,5-b]quinolines, and tetrahydropentaazacyclopenta[a]anthracenes structurally related to some DNA intercalators is described. Fifteen compounds were evaluated for their antitumor activity by the National Cancer Institute (NCI), in vitro disease oriented antitumor screening. The most active tricyclic pyrimido[4,5-b]quinolines 3b, 6b, 7b and 8b were further subjected to DNA-binding investigation in an attempt to rationalize their activity. Compound 8b proved to be the most active member in this study as evidenced from its remarkable growth inhibitory potential against some individual cell lines, and its broad spectrum of antitumor activity (GI50, TGI and LC50 values 46.9, 85.3 and 97.4, respectively), together with a good DNA-binding affinity.
authors.affiliation: Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia.
authors.forename: Hassan M
authors.initials: HM
authors.lastname: Faidallah
authors.forename: Sherif A F
authors.initials: SA
authors.lastname: Rostom
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D018922:HL-60 Cells; D019073:HT29 Cells; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D061986:MCF-7 Cells; D015394:Molecular Structure; D011804:Quinolines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D006575:Heterocyclic Compounds, 3-Ring; D006576:Heterocyclic Compounds, 4 or More Rings; D011804:Quinolines; D004247:DNA; C542964:1,2,3,4-tetrahydroquinoline