Bioinspired thiazolo-[2,3-b] quinazolin-6-one derivatives as potent anti-cancer agents targeting EGFR: their biological evaluations and in silico assessment.
Anti-cancer activity
Apoptosis assay
Molecular modeling
Thiazolo-[2,3-b] quinazolin-6-one derivatives
Journal
Molecular diversity
ISSN: 1573-501X
Titre abrégé: Mol Divers
Pays: Netherlands
ID NLM: 9516534
Informations de publication
Date de publication:
03 Jul 2023
03 Jul 2023
Historique:
received:
27
02
2023
accepted:
25
06
2023
medline:
3
7
2023
pubmed:
3
7
2023
entrez:
3
7
2023
Statut:
aheadofprint
Résumé
Cancer is a challenging and second most deadly disease. The epidermal growth factor receptors (EGFRs) dimerize upon ligand bindings to the extracellular domain that intiates the downstream signaling cascades and activates intracellular kinase domain. Thus, activation of autophosphrylation through kinase domain results in metastasis, cell proliferation, and angiogenesis. In this study, we unravel the binding mechanism of newly synthesized thiazolo-[2,3-b] quinazolin-6-one and evaluate their anti-cancer activity against ovary and prostate carcinoma cell lines (OVCAR-3 and PC-3). Synthesized molecules exhibited promising anti-cancer activity against OVCAR-3 and PC-3 carcinoma cell lines with inhibitory concentrations ranging from 13.4 ± 0.43 to 23.6 ± 1.22 μM and 7.5 ± 0.62 to 67.5 ± 1.24 μM, respectively. These compounds induced apoptosis and resulted in cell cycle arrest at G1 and G2/M transition phases. Next, the nude mice models were taken to investigate the toxicity of the 4bi compound, and in vivo investigations revealed no effects upon examined organs (liver and kidney) treated at different concentrations. Moreover, the combined in silico approaches, molecular docking, molecular dynamics simulations, and MM/PBSA methods were performed to assess the binding affinity and stability of bioinspired synthesized congeners with the epidermal growth factor receptor tyrosine kinase (EGFR-TK). The free binding energy (ΔG
Identifiants
pubmed: 37395840
doi: 10.1007/s11030-023-10688-6
pii: 10.1007/s11030-023-10688-6
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
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