Dihydroquinoline derivative as a potential anticancer agent: synthesis, crystal structure, and molecular modeling studies


Cancer is one of the leading causes of death worldwide and requires intense and growing research investments from the public and private sectors. This is expected to lead to the development of new medicines. A determining factor in this process is the structural understanding of molecules with potential anticancer properties. Since the major compounds used in cancer therapies fail to encompass every spectrum of this disease, there is a clear need to research new molecules for this purpose. As it follows, we have studied the class of quinolinones that seem effective for such therapy. This paper describes the structural elucidation of a novel dihydroquinoline by single-crystal X-ray diffraction and spectroscopy characterization. Topology studies were carried through Hirshfeld surfaces analysis and molecular electrostatic potential map; electronic stability was evaluated from the calculated energy of frontier molecular orbitals. Additionally, in silico studies by molecular docking indicated that this dihydroquinoline could act as an anticancer agent due to their higher binding affinity with human aldehyde dehydrogenase 1A1 (ALDH 1A1). Tests in vitro were performed for VERO (normal human skin keratinocytes), B16F10 (mouse melanoma), and MDA-MB-231 (metastatic breast adenocarcinoma), and the results certified that compound as a potential anticancer agent.

Graphic abstract

A Dihydroquinoline derivative was tested against three cancer cell lines and the results attest that compound as potential anticancer agent.

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The authors would like to acknowledge the Brazilian agencies Fundação de Amparo à Pesquisa do Estado de Goiás (FAPEG), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for financial support. We would like to thank the Universidade Federal de Juiz de Fora for the X-ray diffraction data collection, OpenEye Scientific Software Inc. (https://www.eyesopen.com/), and ChemAxon (https://chemaxon.com) for providing us with an academic license of their software. CHA and HBN are the researcher’s fellows of CNPq.

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WFV and HBN designed the project. JMFC, GDCO, and CNP performed the synthesis, crystallization, and spectroscopies studies of M-CNP. WFV, HBN, and PSCJ performed crystallography studies. JTMF, BJN, and CHA performed the in silico studies. EPSL performed the in vitro studies. All authors have written, critically reviewed, and approved the manuscript.

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Correspondence to W. F. Vaz.

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Vaz, W.F., Custodio, J.M.F., D’Oliveira, G.D.C. et al. Dihydroquinoline derivative as a potential anticancer agent: synthesis, crystal structure, and molecular modeling studies. Mol Divers 25, 55–66 (2021). https://doi.org/10.1007/s11030-019-10024-x

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  • X-ray diffraction
  • Molecular docking
  • ADMET properties
  • Hirshfeld surface
  • Anticancer activity