Amide-tethered quinoline-resorcinol conjugates as a new class of HSP90 inhibitors suppressing the growth of prostate cancer cells |
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| Institution: | 1. School of Traditional Chinese Materia Medica, Key Laboratory of Computational Chemistry-Based Natural Antitumor drug Research & Development, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, People''s Republic of China;2. Xiamen Institute for Food and Drug Quality Control, Xiamen 361012, People''s Republic of China;3. School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China;1. School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, PR China;2. State Key Laboratory of Non-Food Biomass and Enzyme Technology, National Engineering Research Center for Non-Food Biorefinery, Guangxi Key Laboratory of Biorefinery, Guangxi Academy of Sciences, Nanning 530007, PR China;3. School of Animal Science and Technology, Guangxi University, Nanning 530004, PR China |
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| Abstract: | The study is focused on the design and synthesis of amide tethered quinoline-resorcinol hybrid constructs as a new class of HSP90 inhibitor. In-vitro studies of the synthetic compounds led to the identification of compound 11, which possesses potent cell growth inhibitory effects against HCT116, Hep3B and PC-3 cell lines, exerted through HSP90 inhibition. Compound 11 triggers degradation of HSP90 client proteins along with concomitant induction of HSP70, demonstrates apoptosis inducing ability and causes G2M phase cell cycle arrest in PC-3 cells. Molecular modeling was used to dock compound 11 into the HSP90 active site and key interactions with the amino acid residues of the HSP90 chaperone protein were determined. |
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| Keywords: | Quinoline Resorcinol Chaperone Cancer Apoptosis Heat shock protein |
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