Pyrazole-based and N,N-diethylcarbamate functionalized some novel aurone analogs: Design, synthesis, cytotoxic evaluation, docking and SAR studies, against AGS cancer cell line
Ekta Lathwal,
Sanjeev Kumar,
Pranab Kumar Sahoo,
Sushmita Ghosh,
Sutapa Mahata,
Vilas D. Nasare,
Ravikumar Kapavarapu,
Suresh Kumar
Affiliations
Ekta Lathwal
Department of Chemistry, Kurukshetra University, Kurukshetra, 136119, Haryana, India; Govt. College, Tigaon, Faridabad, 121101, Haryana, India
Sanjeev Kumar
Department of Chemistry, Kurukshetra University, Kurukshetra, 136119, Haryana, India; PGT Chemistry, KendriyaVidyalaya Kokrajhar, Assam, 783370, India
Pranab Kumar Sahoo
Department of Pathology and Cancer Screening, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, India
Sushmita Ghosh
Department of Pathology and Cancer Screening, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, India
Sutapa Mahata
Department of Pathology and Cancer Screening, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, India
Vilas D. Nasare
Department of Pathology and Cancer Screening, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, India
Ravikumar Kapavarapu
Department of Pharmaceutical Chemistry and Phytochemistry, Nirmala College of Pharmacy, Atmakur, Mangalagiri, Andhra Pradesh, India
Suresh Kumar
Department of Chemistry, Kurukshetra University, Kurukshetra, 136119, Haryana, India; Corresponding author. Department of Chemistry, Kurukshetra University; Kurukshetra, Haryana, India.
The present study involves the design, synthesis, and biological evaluation of a series of thirty-three, pyrazole-based and N,N-diethylcarbamate functionalized, novel aurone analogs, against AGS cancer cell line. These novel aurone analogs are obtained from the reaction of pyrazole-based 6-hydroxyaurones with diethyl carbamoyl chloride using mild basic reagent. The cytotoxic activities of these compounds were evaluated against a human gastric adenocarcinoma cell line (AGS) and disclosed some potential outcomes as several analogs were found to have cytotoxicity better than the reference drugs Oxaliplatin and Leucovorin. The structure-activity relationship (SAR) study further unveiled the critical role of replacing the hydroxyl group in ring A with a carbamoyl group for cytotoxic activity. Among these aurone analogs, 8e and 8f, with IC50 values of 6.5 ± 0.024 μM and 6.6 ± 0.035 μM, respectively, are identified as the most active compounds. Molecular docking studies were conducted against HER2, a human epidermal growth factor involved in gastric and ovarian cancer, to investigate the binding interactions between the compounds and the protein HER2, where7e and 8e exhibited maximum interactions.
