title: Antitumor agents 295. E-ring hydroxylated antofine and cryptopleurine analogues as antiproliferative agents: design, synthesis, and mechanistic studies.
abstract: 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.
authors: 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.
authors: Xiaoming
authors: X
authors: Yang
authors: Qian
authors: Q
authors: Shi
authors: Chin-Yu
authors: CY
authors: Lai
authors: Chi-Yuan
authors: CY
authors: Chen
authors: Emika
authors: E
authors: Ohkoshi
authors: Shuenn-Chen
authors: SC
authors: Yang
authors: Chih-Ya
authors: CY
authors: Wang
authors: Kenneth F
authors: KF
authors: Bastow
authors: Tian-Shung
authors: TS
authors: Wu
authors: Shiow-Lin
authors: SL
authors: Pan
authors: Che-Ming
authors: CM
authors: Teng
authors: Pan-Chyr
authors: PC
authors: Yang
authors: Kuo-Hsiung
authors: KH
authors: Lee
mesh_terms: D000230:Adenocarcinoma; D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008175:Lung Neoplasms; D010618:Phenanthrolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D054837:Quinolizidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D051176:beta Catenin / Q000096:biosynthesis
chemical_list: C576044:13-hydroxycryptopleurine; D000470:Alkaloids; D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D007211:Indoles; D010618:Phenanthrolines; D054837:Quinolizidines; C473343:antofine; D051176:beta Catenin; C007160:cryptopleurine