Design, synthesis and preliminary in-vitro studies of novel boronated monocarbonyl analogues of Curcumin (BMAC) for antitumor and β-amiloyd disaggregation activity

• Published in: Bioorganic chemistry Vol. 93; p. 103324
• Main Authors: Azzi, Emanuele, Alberti, Diego, Parisotto, Stefano, Oppedisano, Alberto, Protti, Nicoletta, Altieri, Saverio, Geninatti-Crich, Simonetta, Deagostino, Annamaria
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.12.2019; Elsevier
• Subjects: Adenocarcinoma; Alzheimer’s disease; Biochemistry & Molecular Biology; BMAC (Boronated Monocarbonyl Analogues); Chemistry; Chemistry, Organic; Curcumin; Life Sciences & Biomedicine; MAC (Monocarbonyl analogues); Physical Sciences; Science & Technology; Adenocarcinoma; Curcumin; Alzheimer’s disease; MAC (Monocarbonyl analogues); BMAC (Boronated Monocarbonyl Analogues); APOPTOSIS; STABILITY; ENDOPLASMIC-RETICULUM STRESS; CANCER; AMYLOID FIBRILLATION; MEDICINAL CHEMISTRY; NEUTRON-CAPTURE THERAPY; AGENTS; INHIBITORS; Alzheimer's disease; AGGREGATION
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2019.103324

[Display omitted] •Three new boronated monocarbonyl Curcuminoids (BMAC, 6a-c) were designed and prepared.•BMAC antitumor activity against MCF7 and OVCAR-3 cell lines was assessed in vitro and compared to curcumin and MAC.•BMAC 6a-c showed an efficiency comparable to MAC and superior to curcumin.•BMAC 6a-c efficacy in the disaggregation of β-amyloid aggregates was evaluated.•BMAC 6c showed a higher efficiency in the disaggregation of β-amyloids than Curcumin. Curcumin is currently being investigated for its capacity to treat many types of cancer and to prevent the neuron damage that is observed in Alzheimer’s disease (AD). However, its clinical use is limited by its low stability and solubility in aqueous solutions. In this study, we propose a completely new class of boronated monocarbonyl analogues of Curcumin (BMAC, 6a-c), in which a carbonyl group replaces the Curcumin β-diketone functionality, and an ortho-carborane, an icosahedral boron cluster, substitutes one of the two phenolic rings. BMAC antitumor activity against MCF7 and OVCAR-3 cell lines was assessed in vitro and compared to that of Curcumin and the corresponding MAC derivative. BMAC 6a-c showed efficiencies that are comparable to that of MAC and superior to that of Curcumin in both the cell lines. Moreover, the inhibition of the formation of β-amyloid aggregates by BMAC 6a-c was evaluated and it was shown that compound 6c, which contains two OH moieties, has a better efficiency than Curcumin. The presence of a second –OH group can enhance the compound’s binding efficacy with β-amyloid aggregates. For the future, the presence of at least one carborane group means that the BMAC antitumor effect can be coupled with Boron Neutron Capture Therapy.