The College of Pharmacy discussed the PhD dissertation entitled “The Possible Cytotoxic Effects of 2-Thioester-3-Benzoyl-5-Azo Imidazole-4-One against Initiation of Colorectal Cancer in Comparison with 5-Fluorouracil: In Vitro and in Vivo Study” by the student Noor Abdullah Kadhim and the supervisor, Assistant Professor Dr. Ahmed Hamed Jwaid, at the Pharmacology and Toxicology Department.
The study aimed to evaluate the therapeutic efficacy of the compound 2-thioester-3-benzoyl-5-azo-imidazole-4-one against colorectal cancer and compare its effect with that of the drug 5-fluorouracil.
The study included 70 male mice randomly divided into seven groups of 10 and treated as follows: Group I mice received normal saline for nine weeks, followed by 10% DMSO for 14 consecutive days; Group II mice received 20 mg/kg of the carcinogen (1,2-dimethylhydrazine) for 9 weeks, followed by 10% DMSO for 14 consecutive days; Group III mice received normal saline for nine weeks, followed by 400 µg/mL of the test compound (2-thioester-3-benzoyl-5-azo imidazole-4-one) for 14 consecutive days; Group IV mice received 20 mg/kg of the carcinogen for nine weeks, followed by 400 µg/mL of the test compound for 14 consecutive days; Group V mice received 20 mg/kg of the carcinogen for nine weeks, followed by 200 µg/mL of the test compound for 14 consecutive days; Group VI mice received 20 mg/kg of the carcinogen for nine weeks, followed by 50 mg/kg of 5-fluorouracil for 14 consecutive days; Group VII mice received 20 mg/kg of the carcinogen for nine weeks, followed by 50 mg/kg of 5-fluorouracil and 200 µg/mL of the test compound for 14 consecutive days. After that, the mice were sacrificed, and blood and colon tissue samples were collected for histological, biochemical, and gene expression analyses.
The results demonstrated that the 2-thioester-3-benzoyl-5-azo imidazole-4-one compound exhibits potent and selective anticancer activity against colorectal cancer both in vitro and in vivo, with an efficacy comparable to or exceeding that of the standard treatment, 5-fluorouracil. The compound showed high concentration- and time-dependent inhibition of cancer cell proliferation while maintaining an acceptable safety profile toward normal cells. In vivo, it substantially restored normal colonic architecture and reduced elevated tumor marker levels back to baseline. The underlying molecular mechanism involved reversing carcinogenic changes by stimulating apoptotic pathways and enhancing tumor suppressor genes, while concurrently suppressing the Wnt/β-catenin signaling pathway and cytokeratin overexpression, suggesting that it may be a promising therapeutic candidate.
The study recommended elucidating the molecular mechanisms underlying the anticancer activity of the 2-thioester-3-benzoyl-5-azo-imidazole-4-one compound, specifically the Wnt/β-catenin pathway and apoptosis markers, while also conducting comprehensive studies to evaluate its safety, therapeutic window, and pharmacokinetics before proceeding to clinical trials.
