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: [email protected].
  • 6. Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER) - Ahmadabad, Palaj, Gandhinagar-382355, Gujarat, India. Electronic address: [email protected].
  • 7. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER) - Ahmadabad, Palaj, Gandhinagar-382355, Gujarat, India. Electronic address: [email protected].
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.