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Your search keyword '"Qian Shi"' showing total 3 results
3 results on '"Qian Shi"'

1. Antitumor Agents 295. E-Ring Hydroxylated Antofine and Cryptopleurine Analogues as Antiproliferative Agents: Design, Synthesis, and Mechanistic Studies

Author

Chin Yu Lai, Shuenn Chen Yang, Qian Shi, Xiaoming Yang, Che-Ming Teng, Shiow Lin Pan, Kuo Hsiung Lee, Kenneth F. Bastow, Chih Ya Wang, Tian Shung Wu, Pan-Chyr Yang, Emika Ohkoshi, and Chi-Yuan Chen

Subjects
Indoles, Lung Neoplasms, Quinolizidines, Stereochemistry, Down-Regulation, Antineoplastic Agents, Stereoisomerism, Adenocarcinoma, medicine.disease_cause, Article, Structure-Activity Relationship, Alkaloids, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Drug Discovery, medicine, Humans, Structure–activity relationship, HSP90 Heat-Shock Proteins, Hedgehog, beta Catenin, Cell Proliferation, biology, Cell growth, Chemistry, medicine.disease, Hsp90, Cell culture, Drug Design, Cancer research, biology.protein, Molecular Medicine, Drug Screening Assays, Antitumor, Carcinogenesis, Phenanthrolines
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.

Published
2012

2. Antitumor Agents 288: Design, Synthesis, SAR, and Biological Studies of Novel Heteroatom-Incorporated Antofine and Cryptopleurine Analogues as Potent and Selective Antitumor Agents

Author

Kenneth F. Bastow, Chi-Yuan Chen, Qian Shi, Kuo Hsiung Lee, Tian Shung Wu, Sung-Liang Yu, Che-Ming Teng, Xiaoming Yang, Pan-Chyr Yang, Susan L. Morris-Natschke, Chin Yu Lai, Shuenn Chen Yang, Pei Chi Wu, Shiow Lin Pan, and Jau Chen Lin

Subjects
DNA Replication, Indoles, Transplantation, Heterologous, Antineoplastic Agents, Pharmacology, Article, S Phase, Mice, Structure-Activity Relationship, Alkaloids, Cell Line, Tumor, Drug Discovery, medicine, Animals, Structure–activity relationship, Cytotoxicity, Cell growth, Chemistry, DNA replication, Stereoisomerism, In vitro, Transplantation, Mechanism of action, Cell culture, Drug Design, Molecular Medicine, Drug Screening Assays, Antitumor, medicine.symptom, Neoplasm Transplantation, Phenanthrolines
Abstract

Novel heteroatom-incorporated antofine and cryptopleurine analogues were designed, synthesized, and tested against a panel of five cancer cell lines. Two new S-13-oxo analogues (11 and 16) exhibited potent cell growth inhibition in vitro (GI(50): 9 nM and 20 nM). Interestingly, both compounds displayed improved selectivity among different cancer cell lines, in contrast to the natural products antofine and cryptopleurine. Mechanism of action (MOA) studies suggested that R-antofine promotes dysregulation of DNA replication during early S phase, while no similar effects were observed for 11 and 15 on corresponding replication initiation complexes. Compound 11 also showed greatly reduced cytotoxicity against normal cells and moderate antitumor activity against HT-29 human colorectal adenocarcinoma xenograft in mice without overt toxicity.

Published
2011

3. Antitumor Agents 286. Design, Synthesis, and Structure−Activity Relationships of 3′R,4′R-Disubstituted-2′,2′-dimethyldihydropyrano[2,3-f]chromone (DSP) Analogues as Potent Chemosensitizers to Overcome Multidrug Resistance

Author

Kenneth F. Bastow, Ting Zhou, Kuo Hsiung Lee, and Qian Shi

Subjects
Stereochemistry, Antineoplastic Agents, Stereoisomerism, Article, Structure-Activity Relationship, chemistry.chemical_compound, Cell Line, Tumor, Drug Discovery, medicine, Humans, Structure–activity relationship, Drug Interactions, ATP Binding Cassette Transporter, Subfamily B, Member 1, Pyrans, P-glycoprotein, biology, Drug Resistance, Multiple, Multiple drug resistance, Design synthesis, chemistry, Mechanism of action, Chromones, Drug Resistance, Neoplasm, Drug Design, Chromone, biology.protein, Molecular Medicine, Drug Screening Assays, Antitumor, medicine.symptom
Abstract

In this study, various 3'R,4'R-disubstituted-2',2'-dimethydihydropyrano[2,3-f]chromone (DSP) derivatives were discovered as potent chemosensitizers in the treatment of multidrug resistant cancer cells. Twenty-four DSP analogues (5-28) were synthesized and evaluated against a multidrug resistant (MDR) cell line (KB-Vin) with and without vincristine (VCR). All DSP analogues exhibited low intrinsic cytotoxicity. However, in combination treatment, most DSPs reversed resistance to VCR and lowered the GI₅₀ value of VCR by 12-349-fold. At a concentration of 1 μg/mL, three compounds, 11, 14, and 21, fully reversed resistance to VCR in KB-Vin cancer cells, a 2-fold increase compared to verapamil, a first-generation chemosensitizer. Detailed structure-activity relationship (SAR) conclusions were established based on 3' and 4' substitutions. Moreover, a preliminary mechanism study indicated that the chemosensitizing activity of DSP analogues results from inhibition of P-glycoprotein (P-gp) overexpressed in MDR cancer cells.

Published
2010

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