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

Autor: Parshuram Satpute D; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER) - Ahmadabad, Palaj, Gandhinagar-382355, Gujarat, India., Shirwadkar U; Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER) - Ahmadabad, Palaj, Gandhinagar-382355, Gujarat, India., Kumar Tharalla A; Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER) - Ahmadabad, Palaj, Gandhinagar-382355, Gujarat, India., Dattatray Shinde S; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER) - Ahmadabad, Palaj, Gandhinagar-382355, Gujarat, India., Nikhil Vaidya G; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER) - Ahmadabad, Palaj, Gandhinagar-382355, Gujarat, India., Joshi S; Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER) - Ahmadabad, Palaj, Gandhinagar-382355, Gujarat, India., Patel Vatsa P; Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER) - Ahmadabad, Palaj, Gandhinagar-382355, Gujarat, India., Jain A; 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., Singh AA; Department of Molecular Biology, Radboud University, Nijmegen, Netherlands., Garg R; 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., Mandoli A; Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER) - Ahmadabad, Palaj, Gandhinagar-382355, Gujarat, India. Electronic address: amitmandoli@niperahm.res.in., Kumar D; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER) - Ahmadabad, Palaj, Gandhinagar-382355, Gujarat, India. Electronic address: dineshk@niperahm.res.in.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2023 Mar 01; Vol. 81, pp. 117193. Date of Electronic Publication: 2023 Feb 03.
DOI: 10.1016/j.bmc.2023.117193
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: