Search for novel histone deacetylase inhibitors. Part II: Design and synthesis of novel isoferulic acid derivatives |
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| Institution: | 1. Department of Food, Environmental and Nutritional Sciences, Division of Chemistry and Molecular Biology, Università di Milano, Via Celoria 2, 20133 Milano, Italy;2. R&D Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., Via Pontina Km 30,400, I-00040 Pomezia, RM, Italy;3. Molecular Pharmacology Unit, Dept. Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Via Amadeo 42, I-20133 Milan, Italy;1. Institute of Radiation and Irradiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China;2. Department of Medicinal Chemistry, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China;1. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmacy, Shandong University, 44 West Wenhua Rd, Ji’nan 250012, China;2. Shandong Provincial Key Laboratory of Neuroprotective Drug, Shandong Qidu Pharmaceutical Co., Ltd, 250012, China;1. Department of Food, Environmental and Nutritional Sciences, Division of Chemistry and Molecular Biology, University of Milan, via Celoria 2, 20133 Milan, Italy;2. School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, 1211 Geneva 11, Switzerland;3. Fondazione IRCCS Istituto Nazionale Tumori, Via Amadeo 42, 20133 Milano, Italy;4. R&D Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., Via Pontina Km 30,400, I-00071 Pomezia, Roma, Italy;1. School of Pharmaceutical Sciences, Central South University, Changsha 410013, China;2. Drug Discovery Department, Hisun Group, Taizhou 317700, China |
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| Abstract: | Previously, we described the discovery of potent ferulic acid-based histone deacetylase inhibitors (HDACIs) with halogeno-acetanilide as novel surface recognition moiety (SRM). In order to improve the affinity and activity of these HDACIs, twenty seven isoferulic acid derivatives were described herein. The majority of title compounds displayed potent HDAC inhibitory activity. In particular, IF5 and IF6 exhibited significant enzymatic inhibitory activities, with IC50 values of 0.73 ± 0.08 and 0.57 ± 0.16 μM, respectively. Furthermore, these compounds showed moderate antiproliferative activity against human cancer cells. Especially, IF6 displayed promising profile as an antitumor candidate with IC50 value of 3.91 ± 0.97 μM against HeLa cells. The results indicated that these isoferulic acid derivatives could serve as promising lead compounds for further optimization. |
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| Keywords: | Histone deacetylase HDAC inhibitor Isoferulic acid Anticancer |
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