Chalcones derived from Croton anisodontus as potential anticancer agents against human cancer cell lines SNB-19 (glioblastoma), HCT-116 (colon), and PC3 (prostate).

Cláudia Pessoa, Henrique Douglas Melo Coutinho, Wandresa Francelino Pereira, Matheus Numes da Rocha, Emanuelle Machado Marinho, Jaiza Maria Lima Dias, Francisco Wagner de Queiroz Almeida-Neto, Guilherme Graziany Camelo de Carvalho, Marcia Machado Márcia, Emmanuel Silva Marinho, Alexandre Magno Rodrigues Teixeira, Hélcio Silva Dos Santos

Journal: Biochemical and biophysical research communications 2025;758():151612

PMID: 40117975

Full Text on Elsevier Science View on PubMed

Abstract

Chalcones are a class of natural or synthetic compounds with an α, β-unsaturated carbonyl system. From a pharmacological standpoint, they are highly promising substances, particularly due to their diverse pharmacological properties, among them anticancer activity. The present study aims to evaluate through in vitro and in silico studies the cytotoxicity of chalcones derived of the natural product 2-hydroxy-3,4,6-trimethoxyacetophenone isolated from Croton anisodontus, in order to identify compounds with greater antitumor activity. Regarding the cytotoxic activity, it was observed that these chalcones exhibited activity in human cancer cells of colon (HCT-116), prostate (PC3) and glioblastoma brain (SNB-19). The results demonstrated that chalcone containing a fluorine atom at the para position in the B-ring displayed more significant activity against tumor cell lines PC-3 (IC = 4.79 ± 0.72 μM), HCT-116 (IC = 3.94 ± 0.4 μM) and SNB-19 (IC = 3.64 ± 0.69 μM). Molecular docking study confirmed that the synthesized chalcones interacted in the same region of the binding site of the AQ4 inhibitor against HCT-116 and the 6VN inhibitor against SNB19, indicating which have a similar action to the co-crystallized inhibitors, in addition to competing with testosterone against PC-3, since they interact with residues of the Ligand Binding Domain (LBD). In silico study of absorption, distribution, metabolism, and excretion (ADME) showed that chalcones have high cellular permeability, are slightly soluble in water and moderately bound to plasma proteins, which are essential characteristics of compounds that present antitumor activity. Thus, the chalcones derived from Croton anisodontus could be promising prototypes for development new anticancer drugs.

Address: Graduate Program in Biotechnology - RENORBIO, State University of Ceará, Fortaleza, CE, Brazil.; Department of Experimental Oncology, Federal University of Ceará, Fortaleza, Ceará, Brazil.; Center for Exact Sciences and Technology - Chemistry Course, Acaraú Valley State University, Sobral, CE, Brazil.; Graduate Program in Natural Science, State University of Ceará, Fortaleza, Ceará, Brazil; Graduate Program in Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil.; Graduate Program in Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil. Electronic address: [email protected].; Department of Experimental Oncology, Federal University of Ceará, Fortaleza, Ceará, Brazil; Medicine Course, Center for Social Sciences, Health and Technology, Federal University of Maranhão, Imperatriz, MA, Brazil.; Center for Exact Sciences and Technology - Chemistry Course, Acaraú Valley State University, Sobral, CE, Brazil; Graduate Program in Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil.; Graduate Program in Natural Science, State University of Ceará, Fortaleza, Ceará, Brazil.; Graduate Program in Biotechnology - RENORBIO, State University of Ceará, Fortaleza, CE, Brazil; Graduate Program in Natural Science, State University of Ceará, Fortaleza, Ceará, Brazil; Graduate Program in Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil; Course of Physics, State University of Ceará, Campus FAFIDAM, Limoeiro do Norte, CE, Brazil.; Graduate Program in Biotechnology - RENORBIO, State University of Ceará, Fortaleza, CE, Brazil; Center for Exact Sciences and Technology - Chemistry Course, Acaraú Valley State University, Sobral, CE, Brazil; Graduate Program in Natural Science, State University of Ceará, Fortaleza, Ceará, Brazil; Graduate Program in Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil. Electronic address: [email protected].

DOI: 10.1016/j.bbrc.2025.151612

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MeSH Terms: Humans, Chalcones, Croton, Molecular Docking Simulation, Antineoplastic Agents, Cell Line, Tumor, Male, HCT116 Cells, Glioblastoma