Systematic screening of synthetic organochalcogen compounds with anticancer activity using human lung adenocarcinoma spheroids
- Jéssica Eduarda Dos Santos Batista 1, Mariele Borkowski Rodrigues 2, Ivi Juliana Bristot 3, Valquíria Silva 3, Silvia Bernardy 2, Oscar Endrigo Dorneles Rodrigues 2, Luciano Dornelles 2, Fabiano Barbosa Carvalho 4, Francisca Joseli Freitas de Sousa 5, Marilda da Cruz Fernandes 4, Geancarlo Zanatta 6, Félix Alexandre Antunes Soares 7, Fábio Klamt 3
- 1Department of Biochemistry and Molecular Biology, Federal University of Santa Maria (UFSM), Santa Maria, RS, 97105-900, Brazil; Laboratory of Cellular Biochemistry, Department of Biochemistry, Institute of Basic Health Sciences (ICBS), Federal University of Rio Grande Do Sul (UFRGS), Porto Alegre, RS, 90035-003, Brazil; National Institutes of Science and Technology-Translational Medicine (INCT-TM), Brazil.
- 2Department of Chemistry, Federal University of Santa Maria (UFSM), Santa Maria, RS, 97105-900, Brazil.
- 3Laboratory of Cellular Biochemistry, Department of Biochemistry, Institute of Basic Health Sciences (ICBS), Federal University of Rio Grande Do Sul (UFRGS), Porto Alegre, RS, 90035-003, Brazil; National Institutes of Science and Technology-Translational Medicine (INCT-TM), Brazil.
- 4Pathology Laboratory, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, RS, 90050-170, Brazil.
- 5Postgraduate Program in Biochemistry at Federal University of Ceará (UFC), Fortaleza, CE, 60440-900, Brazil.
- 6Department of Biophysics, UFRGS, Porto Alegre, RS, 91501-970, Brazil.
- 7Department of Biochemistry and Molecular Biology, Federal University of Santa Maria (UFSM), Santa Maria, RS, 97105-900, Brazil.
- 0Department of Biochemistry and Molecular Biology, Federal University of Santa Maria (UFSM), Santa Maria, RS, 97105-900, Brazil; Laboratory of Cellular Biochemistry, Department of Biochemistry, Institute of Basic Health Sciences (ICBS), Federal University of Rio Grande Do Sul (UFRGS), Porto Alegre, RS, 90035-003, Brazil; National Institutes of Science and Technology-Translational Medicine (INCT-TM), Brazil.
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View abstract on PubMed
Summary
This summary is machine-generated.New organochalcogen compounds show promise in treating lung adenocarcinoma. These novel agents demonstrated superior anticancer activity compared to cisplatin, offering a potential new therapeutic strategy for this deadly cancer.
Area Of Science
- Medicinal Chemistry
- Oncology
- Drug Discovery
Background
- Lung adenocarcinoma is a major cause of cancer mortality with limited treatment options.
- Elevated oxidative stress markers correlate with aggressive cancer traits and poor patient outcomes.
- Targeting aberrant redox biology presents an innovative strategy for lung adenocarcinoma intervention.
Purpose Of The Study
- To screen novel synthetic organochalcogen compounds for anticancer activity.
- To compare the efficacy of these compounds against cisplatin in lung adenocarcinoma models.
- To explore the therapeutic potential of organochalcogens in lung adenocarcinoma treatment.
Main Methods
- Established A549 human lung adenocarcinoma cell line for single tumor spheroid generation.
- Determined optimal spheroid formation (4 days in vitro) and growth (20 days in vitro).
- Conducted toxic dose-response curves for nine organochalcogen compounds and cisplatin after 24 and 48 hours incubation.
Main Results
- At least two synthetic organochalcogen compounds exhibited significant anticancer activity.
- These compounds outperformed cisplatin in terms of lower lethal dose 50 (LD50), larger drug activity area, and maximum effect amplitude.
- In silico analysis predicted favorable physicochemical and ADME properties for selected compounds.
Conclusions
- Synthetic organochalcogen compounds demonstrate superior efficacy compared to cisplatin for lung adenocarcinoma.
- These compounds represent promising candidates for future therapeutic development.
- This research opens new avenues for lung adenocarcinoma treatment by targeting redox biology.
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