Azetidinone–retinoid hybrids: Synthesis and differentiative effects

• Published in: European journal of medicinal chemistry Vol. 70; pp. 857 - 863
• Main Authors: Pori, Matteo, Galletti, Paola, Soldati, Roberto, Calzà, Laura, Mangano, Chiara, Giacomini, Daria
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 01.12.2013; Elsevier
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Azetidines - chemistry; Azetidines - pharmacology; Cell differentiation; Cell Differentiation - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Chemistry, Medicinal; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Epigenetic regulation; HDAC inhibitors; Humans; Life Sciences & Biomedicine; Molecular Structure; Pharmacology & Pharmacy; Retinoids; Retinoids - chemistry; Retinoids - pharmacology; Science & Technology; Structure-Activity Relationship; Synthesis; β-Lactams; HDAC inhibitors; Synthesis; Retinoids; Epigenetic regulation; Cell differentiation; β-Lactams; APOPTOSIS; CELLS; ACID; CRYSTAL-STRUCTURE; ANTICANCER BETA-LACTAMS; beta-Lactams; INDUCTION; INHIBITORS; BINDING; DERIVATIVES; EXPRESSION
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2013.09.057

As a part of a systematic investigation on the synthesis and biological activities of new β-lactam compounds, we examined β-lactam candidates 1, 2E and 2Z and their ability to induce cell proliferation or differentiation. Azetidinone 1 was chosen for its activity (previously evaluated) as selective HDAC8 inhibitor, whereas β-lactams 2E and 2Z were designed to have a hybrid retinoid-azetidinone structure, de novo synthesized and fully characterized. Biological activities were determined in cellular assays on neuroblastoma cells SH-SY5Y. Azetidinone 1, 2E and 2Z led to a moderate effect in decreasing SH-SY5Y cell proliferation and β-lactams 2E and 2Z induced an early stage differentiation. The present results uncovered a new role of specifically designed β-lactam compounds in epigenetic regulation. [Display omitted] •Synthesis of new β-lactam retinoid–azetidinone hybrids were reported.•Three azetidinone molecules were evaluated on neuroblastoma cells.•Differentiative effects were evaluated.