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Curcumin-cinnamaldehyde hybrids as antiproliferative agents against women’s cancer cells

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Abstract

Curcumin and cinnamaldehyde are natural products whose antineoplastic activity has been well explored in biological evaluations. However, their poor chemical stability under physiological conditions has been an obstacle to their use as therapeutic agents. Herein, we designed and synthesized two series of curcumin-cinnamaldehyde hybrids by removing reactive functionalities, including β-diketone and aldoxyl moieties. All compounds were evaluated by the MTT assay to determine their antiproliferative activity against women’s cancer cells. Compound 5a (3′-hydroxychalcone) demonstrated potent antiproliferative activity against all cancer cell lines tested, with IC50 values ranging from 2.7 to 36.5 µM. Compound 5a was more active and selective than curcumin and cinnamaldehyde (parent compounds) against the CaSki, SiHa, C33, and A431 cell lines, displaying a higher selectivity index (SI = 8.5) than curcumin (SI = 0.8) toward the non-tumorigenic HaCaT cell line. Clonogenic experiments indicated that compound 5a inhibited A431 colony formation in a concentration-dependent manner. In addition, 5a was more stable than its parent compounds in pH 7.4 at 37 °C. In silico investigations suggested that 5a has good drug-likeness properties. In conclusion, our results indicate the use of curcumin and cinnamaldehyde as parent compounds for the design of hybrids with attractive antiproliferative activity and chemical stability.

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Acknowledgements

The authors gratefully acknowledge financial support from the Coordination for the Improvement of Higher Education Personnel (CAPES, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Finance Code 001), Brazilian Council for Scientific and Technological Development (CNPq, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Grants #471129/2013-5, 306251/2016-7, 429322/2018-6 and 309957/2019-2), and São Paulo Research Foundation (FAPESP, Fundação de Amparo à Pesquisa do Estado de São Paulo, Grants #2014/18330-0 and 2018/15083-2). D.B.A. thanks CAPES (Finance Code 001) for the scholarships granted. All authors thank the Center for Biomolecular Innovation (FAPESP Grant #2009/53989-4), National Institute of Science and Technology – Biodiversity and Natural Products INCT-BioNat (FAPESP #2014/50926-0 and CNPq #465637/2014-0), and National Institute of Science and Genomics Technology for Citrus Improvement INCT-Citrus (FAPESP #2014/50880-0 and CNPq #465440/2014- 2). The authors thank Kerstin Markendorf, a native translator, for English translation and scientific writing contributions.

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Authors and Affiliations

  1. Laboratory of Antibiotics and Chemotherapeutics, Department of Chemistry and Environmental Sciences, Institute of Biosciences, Humanities and Exact Sciences, São Paulo State University (Unesp), São José do Rio Preto, SP, 15054-000, Brazil

    Daiane B. Anselmo, Carlos R. Polaquini, Beatriz C. Marques, Gabriela M. Ayusso, Letícia R. Assis, Guilherme S. Torrezan & Luis O. Regasini

  2. Laboratory of Genomic Studies, Department of Biology, Institute of Biosciences, Humanities and Exact Sciences, São Paulo State University (Unesp), São José do Rio Preto, SP, 15054-000, Brazil

    Paula Rahal & Marília F. Calmon

  3. Laboratory of Molecular Genetics and Bioinformatics, Biotechnology Unit, University of Ribeirão Preto (Unaerp), Ribeirão Preto, SP, 14096-900, Brazil

    Ana L. Fachin & Mozart A. Marins

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  1. Daiane B. Anselmo
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Anselmo, D.B., Polaquini, C.R., Marques, B.C. et al. Curcumin-cinnamaldehyde hybrids as antiproliferative agents against women’s cancer cells. Med Chem Res 30, 2007–2015 (2021). https://doi.org/10.1007/s00044-021-02783-w

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