Novologues containing a benzamide side chain manifest anti-proliferative activity against two breast cancer cell lines |
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| Institution: | 1. N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991, Russia;2. S.N. Winogradsky Institute of Microbiology, Russian Academy of Sciences, Moscow 117312, Russia;1. Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan;2. Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan;3. Department of Biochemistry & Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan;4. Institute of Molecular Sciences & Bioinformatics, Lahore 54000, Pakistan;1. Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;2. Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran;3. School of Cell and Molecular Biology, University of Illinois at Urbana-Champaign, Urbana, United States;4. Department of Molecular Medicine, Golestan University of Medical Sciences, Golestan, Iran;5. Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;6. Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran;7. Department of Medical Parasitology and Mycology, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran;1. University of Maryland, Baltimore, MD, USA;2. McMaster University, Hamilton, Canada;1. Chemical Kinomics Research Center, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea;2. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt;3. Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt;4. Medicinal Chemistry Laboratory, Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea;5. Department of Fundamental Pharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea;6. Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea;7. Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea;8. Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of Korea |
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| Abstract: | Hsp90 represents a promising target for the development of both anti-cancer and neuroprotective agents. Structure–activity relationship studies on novobiocin and novobiocin analogues, led to the development of KU-32 and recently, KU-596, as lead compounds for the potential treatment of neurodegenerative diseases. Similar to KU-32, we have demonstrated that upon replacement of the acetamide side chain present in KU-32 with a benzamide, this neuroprotective agent was transformed into a scaffold that manifests anti-proliferative activity. To assess structure–activity relationships for this new scaffold, a library of benzamide-containing novologues was prepared and evaluated against two breast cancer cell lines. Compound 14a manifested the most potent anti-proliferative activity from these studies and induced Hsp90-dependent client protein degradation in a concentration-dependent manner. |
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| Keywords: | Heat shock protein 90 Hsp90 inhibitors Novobiocin analogues Breast cancer |
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