Antitumor agents 253. Design, synthesis, and antitumor evaluation of novel 9-substituted phenanthrene-based tylophorine derivatives as potential anticancer agents

CHE-MING TENG2018-09-102018-09-102007http://www.scopus.com/inward/record.url?eid=2-s2.0-34547610794&partnerID=MN8TOARShttp://scholars.lib.ntu.edu.tw/handle/123456789/328305C9-Substituted phenanthrene-based tylophorine derivatives (PBTs) (13-36) were synthesized and evaluated as in vitro anticancer agents against the human A549 lung cancer cell line. Twelve active compounds were further examined against DU-145 (prostate), ZR-751 (breast), KB (nasopharyngeal), and KB-Vin (multidrug resistant KB subline) human cancer cell lines. They showed potent cytotoxic activity against both wild type and matched multidrug resistant KB cell lines, and displayed notable selectivity toward DU-145 (prostate) and ZR-751 (breast) cancer cell lines. The mode of action of this class may be distinctly different from that of other cancer chemotherapeutic compounds. Three PBT analogs were also evaluated in a murine model. Compound 24b showed modest in vivo antitumor activity against human A549 xenograft in nude mice as well as potent in vitro cytotoxic activity, and thus, is a promising anticancer lead compound. ? 2007 American Chemical Society.[SDGs]SDG3n (2,3 methylenedioxy 6 methoxyphenanthr 9 ylmethyl) 4 piperidineethanol; n (2,3 methylenedioxy 6 methoxyphenanthr 9 ylmethyl) 4 piperidinemethanol; n (2,3 methylenedioxy 6 methoxyphenanthr 9 ylmethyl) 6 aminohexanol; phenanthrene derivative; tylophorine; unclassified drug; animal experiment; animal model; animal tissue; antineoplastic activity; article; cancer; cancer cell culture; cancer model; cell strain KB; controlled study; culture medium; drug cytotoxicity; drug design; drug mechanism; drug structure; drug synthesis; evaluation; human; human cell; male; mouse; multidrug resistance; nonhuman; nude mouse; proton nuclear magnetic resonance; reaction analysis; SCID mouse; structure analysis; tumor xenograft; Alkaloids; Animals; Antineoplastic Agents; Cell Line, Tumor; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Humans; Indolizines; Male; Mice; Mice, Nude; Neoplasm Transplantation; Phenanthrenes; Structure-Activity Relationship; Transplantation, HeterologousAntitumor agents 253. Design, synthesis, and antitumor evaluation of novel 9-substituted phenanthrene-based tylophorine derivatives as potential anticancer agentsjournal article10.1021/jm061366a