Discovery of fluorinated 2‑Styryl 4(3H)-quinazolinone as potential therapeutic hit for oral cancer. (1st March 2023)

• Record Type: Journal Article
• Authors: Parshuram Satpute, Dinesh; Shirwadkar, Urjita; Kumar Tharalla, Anil; Dattatray Shinde, Sangita; Nikhil Vaidya, Gargi; Joshi, Swarali; Patel Vatsa, Priyanka; Jain, Alok; Singh, Abhishek A; Garg, Rachana; Mandoli, Amit; Kumar, Dinesh
• Is Part Of: Bioorganic & medicinal chemistry. Volume 81(2023)
• Publication Date: 2023-03-01
• Subjects: Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2023.117193
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Highlights: ( E )-2-(4-Fluorostyryl)quinazolin-4(3 H )-one was discovered as a promising hit as oral cancer chemotherapeutics. Compound blocks the transition of the G1 to S phase, thereby leading to arrest in the G1/S phase. Compound induces both the activation of molecular pathways involved in regulating cell growth and apoptosis as well as suppresses the pathways of cellular growth. Predicted ADME properties were found favorable. 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 2‑styryl 4(3 H )-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.