Design,synthesis and biological evaluation of β-boswellic acid based HDAC inhibitors as inducers of cancer cell death |
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| Institution: | 1. Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy;2. Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche “Mario Negri” IRCCS, Milano, Italy;3. ANANAS Nanotech S.r.l., Padova, Italy;4. Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche “Mario Negri” IRCCS, Milano, Italy;5. Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy;6. European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy;7. International Center for Digestive Diseases |
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| Abstract: | The synthesis and bio-evaluation of naturally occurring boswellic acids (BAs) as an alternate CAP for the design of new HDAC inhibitors is described. All the compounds were screened against a panel of human cancer cell lines to identify leads, which were subsequently examined for their potential to inhibit HDACs. The identified lead compound showed IC50 value of 6 μm for HDACs, found to induce G1 cell cycle arrest at significantly low concentration (1 μM) and caused significant loss in mitochondrial membrane potential at 5 and 10 μM. Furthermore, specific interactions of the lead molecule inside the catalytic domain were also studied through in silico molecular modeling. |
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| Keywords: | β-Boswellic acid Anti-cancer HDAC Hydroxamic acid |
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