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

Bioorg Med Chem. 2023 Mar 1:81:117193. doi: 10.1016/j.bmc.2023.117193.

Dinesh Parshuram Satpute ¹, Urjita Shirwadkar ², Anil Kumar Tharalla ², Sangita Dattatray Shinde ¹, Gargi Nikhil Vaidya ¹, Swarali Joshi ², Priyanka Patel Vatsa ², Alok Jain ³, Abhishek A Singh ⁴, Rachana Garg ⁵, Amit Mandoli ⁶, Dinesh Kumar ⁷

Affiliations

1 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER) - Ahmadabad, Palaj, Gandhinagar-382355, Gujarat, India.
2 Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER) - Ahmadabad, Palaj, Gandhinagar-382355, Gujarat, India.
3 Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER) - Ahmadabad, Palaj, Gandhinagar-382355, Gujarat, India; Department of Bio-engineering and Biotechnology, Birla Institute of Technology, Mesra, Ranchi, India.
4 Department of Molecular Biology, Radboud University, Nijmegen, Netherlands.
5 Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER) - Ahmadabad, Palaj, Gandhinagar-382355, Gujarat, India; Division of Neurosurgery, Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA. Electronic address: rachana.garg@gmail.com.
6 Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER) - Ahmadabad, Palaj, Gandhinagar-382355, Gujarat, India. Electronic address: amitmandoli@niperahm.res.in.
7 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER) - Ahmadabad, Palaj, Gandhinagar-382355, Gujarat, India. Electronic address: dineshk@niperahm.res.in.

PMID: 36796126 DOI: 10.1016/j.bmc.2023.117193

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(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.

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