Synthesis and biological evaluation of farnesylthiosalicylamides as potential anti-tumor agents |
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| Affiliation: | 1. Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah, 21589, Saudi Arabia;2. Nanoscience Research Laboratory, Department of Chemistry, Jamia Millia Islamia (Central University), New Delhi, 110025, India;1. Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan;2. Division of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, Japan;3. Department of Clinical Medicine (Biostatistics), School of Pharmacy, Kitasato University, Tokyo, Japan;1. Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan 602-714, South Korea;2. Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, South Korea;3. Department of Oral Anatomy and Cell Biology, School of Dentistry, Yangsan Campus of Pusan National University, Yangsan 626-870, South Korea;4. Departments of Dental Pharmacology and Biophysics, School of Dentistry and Research Institute for Oral Biotechnology, Yangsan Campus of Pusan National University, Yangsan 626-870, South Korea;1. Technische Universität Chemnitz, Faculty of Natural Sciences, Institute of Chemistry, Inorganic Chemistry, 09107 Chemnitz, Germany |
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| Abstract: | Fourteen hybrids of farnesylthiosalicylic acid (FTS) with various diamines were synthesized and biologically evaluated. It was found that FTS-monoamide molecules (10a–g) displayed strong anti-proliferative activity against seven human cancer cell lines, superior to FTS and FTS-bisamide compounds (11a–g). The mono-amide 10f was the most active, with IC50s of 3.78–7.63 μM against all tested cancer cells, even more potent than sorafenib (9.12–22.9 μM). In addition, 10f induced SMMC-7721 cell apoptosis, down-regulated the expression of Bcl-2 and up-regulated Bax and caspase-3. Furthermore, 10f had the improved aqueous solubility relative to FTS. Finally, treatment with 10f dose-dependently inhibited the Ras-related signaling pathways in SMMC-7721 cells. Collectively, 10f could be a promising candidate for the intervention of human cancers. |
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| Keywords: | Farnesylthiosalicylic acid Diamines Cell apoptosis Ras-related signaling pathway Anti-cancer agents |
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