resumo
Glioblastoma multiforme (GBM) is an aggressive and treatment-resistant brain tumor. The expansion of a phenolic Mannich base library via the Petasis reaction unexpectedly led to the unsymmetrical tetrahydroquinoline-derived triarylmethanes, confirmed by single-crystal X-ray diffraction. Optimization of reaction conditions revealed the influence of solvent, temperature, and substituent patterns on product yield and regioselectivity. Several of the newly synthesized triarylmethanes demonstrated potent cytotoxicity against human GBM cell lines LN229 and SNB19, with compound 8a ' exhibiting IC50 values (35.3 mu M and 23.5 mu M, respectively) significantly lower than those of the standard chemotherapeutic agent temozolomide (309.7 mu M and 344.4 mu M, respectively). In addition to inhibiting cell proliferation, 8a ' disrupted GBM cell migration in scratch assays, suggesting a strong link between cytotoxicity and impaired motility. The SiRNA experiment confirmed that the specific interaction of 8a ' with EGFR modulates intracellular calcium levels in GBM. These findings highlight the therapeutic potential of triarylmethane scaffolds in GBM treatment via EGFR interaction and underscore the importance of fine-tuning multicomponent reactions to discover biologically active chemotypes.
palavras-chave
QUINONE METHIDES; DERIVATIVES; INHIBITORS; ALKYLATION; WATER; ACIDS
categoria
Biochemistry & Molecular Biology; Pharmacology & Pharmacy
autores
Branco, DSN; Yektaei, ZH; Chandrabose, S; Paz, FAA; Kandhavelu, M; Candeias, NR
nossos autores
Filipe Alexandre Almeida Paz
Investigador PrincipalProjectos
CICECO - Aveiro Institute of Materials (UIDB/50011/2020)
CICECO - Aveiro Institute of Materials (UIDP/50011/2020)
Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)
Collaboratory for Emerging Technologies, CoLab (EMERGING TECHNOLOGIES)
agradecimentos
This work received financial support from PT national funds (FCT/MCTES, Fundac & atilde;o para a Ciencia e Tecnologia and Ministerio da Ciencia, Tecnologia e Ensino Superior) through the projects PTDC/QUI-QOR/1786/2021, UID/50006, UIDB/50011/2020, UIDP/50011/2020, and LA/P/0006/2020. Part of the work was developed within the scope of the project CICECO - Aveiro Institute of Materials, UID/50011/2025 & LA/P/0006/2020 (DOI: https://doi.org/10.54499/LA/P/0006/2020), financed by national funds through the FCT/MCTES (PIDDAC).