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

Emanuele Azzi; Diego Alberti; Stefano Parisotto; Alberto Oppedisano; Nicoletta Protti; Saverio Altieri; Simonetta Geninatti-Crich; Annamaria Deagostino

doi:10.1016/j.bioorg.2019.103324

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

Bioorg Chem. 2019 Dec:93:103324. doi: 10.1016/j.bioorg.2019.103324. Epub 2019 Sep 27.

Authors

Emanuele Azzi¹, Diego Alberti², Stefano Parisotto¹, Alberto Oppedisano¹, Nicoletta Protti³, Saverio Altieri³, Simonetta Geninatti-Crich⁴, Annamaria Deagostino⁵

Affiliations

¹ Department of Chemistry, University of Turin, via P. Giuria 7, 10125 Turin, Italy.
² Department of Molecular Biotechnology and Health Sciences, University of Turin, via Nizza 52, 10126 Turin, Italy.
³ Department of Physics, University of Pavia, via Agostino Bassi 6, Pavia 27100, Italy; Nuclear Physics National Institute (INFN), Unit of Pavia, via Agostino Bassi 6, Pavia 27100, Italy.
⁴ Department of Molecular Biotechnology and Health Sciences, University of Turin, via Nizza 52, 10126 Turin, Italy. Electronic address: simonetta.geninatti@unito.it.
⁵ Department of Chemistry, University of Turin, via P. Giuria 7, 10125 Turin, Italy. Electronic address: annamaria.deagostino@unito.it.

PMID: 31585269
DOI: 10.1016/j.bioorg.2019.103324

Abstract

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.

Keywords: Adenocarcinoma; Alzheimer’s disease; BMAC (Boronated Monocarbonyl Analogues); Curcumin; MAC (Monocarbonyl analogues).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyloid beta-Peptides / drug effects*
Antineoplastic Agents / pharmacology*
Boron Compounds / chemical synthesis
Boron Compounds / chemistry*
Boron Compounds / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Curcumin / chemistry*
Curcumin / pharmacology*
Drug Design*
Drug Screening Assays, Antitumor
Humans

Substances

Amyloid beta-Peptides
Antineoplastic Agents
Boron Compounds
Curcumin