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Bioorg Med Chem ; 81: 117193, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36796126

ABSTRACT

Oral squamous cell carcinoma (OSCC) is the most common malignant epithelial neoplasm, affects the mouth and throat, and accounts for 90 % of oral cancers. Considering the associated morbidity with neck dissections and the limitation of existing therapeutic agents, the discovery and development of new anticancer drugs/drug candidates for oral cancer treatment are of the utmost need. In this context, reported here is the identification of fluorinated 2­styryl 4(3H)-quinazolinone as a promising hit for oral cancer. Preliminary studies indicate that the compound blocks the transition of G1 to S phase, thereby leading to arrest in the G1/S phase. Subsequent RNA-seq analysis revealed that the compound induces the activation of molecular pathways involved in apoptosis (such as TNF signalling through NF-κB, p53 pathways) and cell differentiation and suppresses the pathways of cellular growth and development (such as KRAS signaling) in CAL-27 cancer cells. It is noted that identified hit complies with a favorable range of ADME properties as per the computational analysis.


Subject(s)
Carcinoma, Squamous Cell , Mouth Neoplasms , Humans , Apoptosis , Cell Line, Tumor , Cell Proliferation , Mouth Neoplasms/drug therapy , Mouth Neoplasms/pathology , Signal Transduction
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