Design,synthesis and biological evaluation of novel antitumor spirodihydrothiopyran-oxindole derivatives |
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| Institution: | 1. Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia;2. Department of Chemistry, School of Physical, Chemical & Applied Sciences, Pondicherry University, R.V. Nagar, Kalapet, Puducherry 605014, India;3. Organic & Bioorganic Chemistry Laboratory, CSIR-Central Leather Research Institute, Chennai 600020, Tamil Nadu, India;4. Department of Fundamental Sciences, Faculty of Engineering, Samsun University, Samsun, 55420, Turkey;5. Department of Physics, Faculty of Arts and Sciences, Ondokuz May?s University, Samsun, 55139, Turkey;6. Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, A.P. 515134, India |
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| Abstract: | Sulfur containing spiroheterocyclic oxindoles are promising privileged scaffolds in medicinal chemistry and drug discovery. Previously, we identified a new class of spirodihydrothiopyran-oxindoles with good in vitro antitumor activity against A549 lung cancer cell line. Herein, various spirooxindole-dihydrothiopyrans with diverse substitutions were synthesized and assayed to investigate the structure-activity relationships. Among the derivatives, compounds 4b, 4i, 4m, 4n and 4q displayed superior or comparable antitumor activity than nutlin-3. Molecular mechanism study revealed this scaffold displayed moderate MDM2 inhibitory activity, significantly induced cancer cell apoptosis and arrested cell cycle at G0/G1 phase, which represented a good lead compound for antitumor drug discovery. |
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| Keywords: | Spirodihydrothiopyran oxindole p53-MDM2 inhibitors Antitumor activity |
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