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Synthesis and proapoptotic activity of oleanolic acid derived amides
Affiliation:1. Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany;2. Victor-Babes-University of Medicine and Pharmacy, Department of Pathophysiology and Department of Pharmacognosy, Eftimie Murgu Sq., 30004, 300173 Timisoara, Romania;3. University of Nizwa, Chair of Oman’s Medicinal Plants and Marine Natural Products, PO Box 33, Birkat Al-Mauz, Nizwa, Oman;1. Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases and State Key Laboratory of Natural Medicines, Center of Drug Discovery, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China;2. Department of Medicinal Chemistry, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China;3. Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China;1. Institute of Experimental Botany AS CR, v.v.i., Isotope Laboratory, Vídeňská 1083, 14220 Prague 4, Czech Republic;2. Institute of Chemical Technology, Faculty of Food and Biochemical Technology, Department of Chemistry of Natural Compounds, Technická 5, 16628 Prague 6, Czech Republic;3. Centre of the Region Haná for Biotechnological and Agricultural Research, Faculty of Science, Palacký University, Šlechtitelů 11, 78371 Olomouc, Czech Republic;4. Department of Microbiology, Faculty of Medicine and Dentistry, Palacký University, Hněvotinská 3, 77515 Olomouc, Czech Republic;5. Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nám. 2, 16610 Prague 6, Czech Republic;1. Departamento de Quimica Organica, Facultad de Ciencias, Universidad de Granada, E-18071 Granada, Spain;2. Departamento de Bioquimica y Biologia Molecular I, Facultad de Ciencias, Universidad de Granada, E-18071 Granada, Spain;3. Institute for Research in Biomedicine and CIBER BBN, Baldiri Reixac 10, 08028 Barcelona, Spain;4. School of Chemistry and Physics, University of KwaZulu-Natal, 4001 Durban, South Africa;1. Ufa Institute of Chemistry UFRC RAS, pr. Octyabrya 71, 450054 Ufa, Russian Federation;2. Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany;1. Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Granada, E-18071, Granada, Spain;2. Departamento de Bioquímica y Biología Molecular I, Facultad de Ciencias, Universidad de Granada, E-18071, Granada, Spain
Abstract:Thirty-one different 3-O-acetyl-OA derived amides have been prepared and screened for their cytotoxic activity. In the SRB assays nearly all the carboxamides displayed good cytotoxicity in the low μM range for several human tumor cell lines. Low EC50 values were obtained especially for the picolinylamides 14–16, for a N-[2-(dimethylamino)-ethyl] derivative 27 and a N-[2-(pyrrolinyl)-ethyl] carboxamide 28. These compounds were submitted to an extensive biological testing and proved compound 15 to act mainly by an arrest of the tumor cells in the S phase of the cell cycle. Cell death occurred by autophagy while compounds 27 and 28 triggered apoptosis.
Keywords:Oleanolic acid  Amides  Tumor cells  Cell-cycle arrest  Apoptosis  Autophagy
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