Antitumor agents 295. E-ring hydroxylated antofine and cryptopleurine analogues as antiproliferative agents: design, synthesis, and mechanistic studies.

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Tytuł:: Antitumor agents 295. E-ring hydroxylated antofine and cryptopleurine analogues as antiproliferative agents: design, synthesis, and mechanistic studies.
Autorzy:: Yang X; Natural Products Research Laboratories and ‡Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina , Chapel Hill, North Carolina 27599-7568, United States.
Shi Q
Lai CY
Chen CY
Ohkoshi E
Yang SC
Wang CY
Bastow KF
Wu TS
Pan SL
Teng CM
Yang PC
Lee KH
Źródło:: Journal of medicinal chemistry [J Med Chem] 2012 Aug 09; Vol. 55 (15), pp. 6751-61. Date of Electronic Publication: 2012 Jul 23.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: Washington Dc : American Chemical Society
Original Publication: [Easton, Pa.] : American Chemical Society, [c1963-
MeSH Terms:: Alkaloids/*chemical synthesis
Antineoplastic Agents/*chemical synthesis
Indoles/*chemical synthesis
Phenanthrolines/*chemical synthesis
Quinolizidines/*chemical synthesis
Adenocarcinoma ; Alkaloids/chemistry ; Alkaloids/pharmacology ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Carcinoma, Non-Small-Cell Lung ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Down-Regulation ; Drug Design ; Drug Screening Assays, Antitumor ; HSP90 Heat-Shock Proteins/biosynthesis ; Humans ; Indoles/chemistry ; Indoles/pharmacology ; Lung Neoplasms ; Phenanthrolines/chemistry ; Phenanthrolines/pharmacology ; Quinolizidines/chemistry ; Quinolizidines/pharmacology ; Stereoisomerism ; Structure-Activity Relationship ; beta Catenin/biosynthesis
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Grant Information:: R01 CA017625 United States CA NCI NIH HHS; CA 17625 United States CA NCI NIH HHS
Substance Nomenclature:: 0 (13-hydroxycryptopleurine)
0 (Alkaloids)
0 (Antineoplastic Agents)
0 (HSP90 Heat-Shock Proteins)
0 (Indoles)
0 (Phenanthrolines)
0 (Quinolizidines)
0 (antofine)
0 (beta Catenin)
3JZK58H75B (cryptopleurine)
Entry Date(s):: Date Created: 20120725 Date Completed: 20121105 Latest Revision: 20211021
Update Code:: 20240104
PubMed Central ID:: PMC3422873
DOI:: 10.1021/jm3001218
PMID:: 22823514
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Various E-ring hydroxylated antofine and cryptopleurine analogues were designed, synthesized, and tested against five human cancer cell lines. Interesting structure-activity relationship (SAR) correlations were found among these new compounds. The most potent compound 13b was further tested against a series of nonsmall cell lung cancer (NSCLC) cell lines in which it showed impressive antiproliferative activity. Mechanistic studies revealed that 13b is able to down-regulate HSP90 and β-catenin in A549 lung adenocarcinoma cells in a dose-dependent manner, suggesting a potential use for treating hedgehog pathway-driven tumorigenesis.

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