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Background: Head and neck squamous cell carcinoma (HNSCC) is one of the major types of cancer, with 900,000 cases and over 400,000 deaths annually. It constitutes 3-4% of all cancers in Europe and western countries. As early diagnosis is the key to treating the disease, reliable biomarkers play an important role in the precision medicine of HNSCC. Despite treatments, the survival rate of cancer patients remains unchanged, and this is mainly due to the failure to detect the disease early. Thus, the objective of this study is to identify reliable biomarkers for head and neck cancers for better healthcare management. Methods: In this study, all available, curated human genes were screened for their expression against HNSCC TCGA patient samples using genomic and proteomic data by various bioinformatic approaches and datamining. Docking studies were performed using AutoDock or online virtual screening tools for identifying potential ligands. Results: Sixty genes were short-listed, and most of them show a consistently higher expression in head and neck patient samples at both the mRNA and the protein level. Irrespective of human papillomavirus (HPV) status, all of them show a higher expression in cancer samples. The higher expression of 30 genes shows adverse effects on patient survival. Out of the 60 genes, 12 genes have crystal structures and druggable potential. We show that genes such as GTF2H4, HAUS7, MSN, and MNDA could be targets of Pembrolizumab and Nivolumab, which are approved monoclonal antibodies for HNSCC. Conclusion: Sixty genes are identified as potential biomarkers for head and neck cancers based on their consistent and statistically significantly higher expression in patient samples. Four proteins have been identified as potential drug targets based on their crystal structure. However, the utility of these candidate genes has to be further tested using patient samples., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

To discover anticancer drugs with novel structures and expand our research scope, pyrazoline derivatives ( 3a - 3l ) were designed and synthesized through cyclization of chalcones with thiosemicarbazide/semicarbazide in CH 3 COOH as a solvent. All newly synthesized pyrazoline derivatives were fully characterized using several spectroscopic experiments such as 1 H, 13 C NMR, FT-IR spectroscopy, and mass analysis. By HPLC , the purity of all analogs was found above 95% and both lead compounds ( 3a and 3h ) were also validated by HRMS . Anticancer activity of synthesized pyrazoline derivatives ( 3a - 3l ) was investigated by the MTT assay against the human lung cancer cell (A549), human cervical cancer cell (HeLa), and human primary normal lung cells (HFL-1). Staurosporine (STS) was used as a standard drug. The anticancer results showed that two potent analogs 3a and 3h exhibit excellent activity against A549 (IC 50 = 13.49 ± 0.17 and 22.54 ± 0.25 μM) and HeLa cells (IC 50 = 17.52 ± 0.09 and 24.14 ± 0.86 μM) and low toxicity against the HFL-1 (IC 50 = 114.50 ± 0.01 and 173.20 ± 10 μM). The flow cytometry was further used to confirm the anticancer activity of potent derivatives against the A549 cancer cell line. DNA binding interaction of anticancer agents 3a and 3h with Ct-DNA has been carried out by absorption, fluorescence, EtBr (dye displacement assay), circular dichroism, cyclic voltammetry and time-resolved fluorescence, which showed noncovalent binding mode of interaction. Anticancer activity of both lead compounds ( 3a and 3h ) may be attributed to DNA binding. The evaluation of the antioxidant potential of pyrazoline analogs 3a and 3h by 2,2-diphenyl-1-picrylhydrazyl free radical showed promising antioxidant activity with IC 50 values of 0.132 ± 0.012 and 0.215 ± 0.025 μg/mL, respectively. In silico molecular docking of pyrazoline derivatives was also performed using autodock vina software against the DNA hexamer with PDB ID: 1Z3F and ADMET properties to explore their best hits., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

In vivo targeting and visualization of cyclooxygenase-1 (COX-1) using multimodal positron emission tomography/computed tomography imaging represents a unique opportunity for early detection and/or therapeutic evaluation of ovarian cancer because overexpression of COX-1 has been characterized as a pathologic hallmark of the initiation and progression of this disease. The furanone core is a common building block of many synthetic and natural products that exhibit a wide range of biological activities. We hypothesize that furanone-based COX-1 inhibitors can be designed as imaging agents for the early detection, delineation of tumor margin, and evaluation of treatment response of ovarian cancer. We report the discovery of 3-(4-fluorophenyl)-5,5-dimethyl-4-( p -tolyl)furan-2(5 H )-one (FDF), a furanone-based novel COX-1-selective inhibitor that exhibits adequate in vivo stability, plasma half-life, and pharmacokinetic properties for use as an imaging agent. We describe a novel synthetic scheme in which a Lewis acid-catalyzed nucleophilic aromatic deiodo[ 18 F]fluorination reaction is utilized for the radiosynthesis of [ 18 F]FDF. [ 18 F]FDF binds efficiently to COX-1 in vivo and enables sensitive detection of ovarian cancer in subcutaneous and peritoneal xenograft models in mice. These results provide the proof of principle for COX-1-targeted imaging of ovarian cancer and identify [ 18 F]FDF as a promising lead compound for further preclinical and clinical development., Competing Interests: The authors declare no competing financial interest.