Design, Synthesis and Evaluation of Core Scaffold Pyrazolone Fused Thiazolidinone Derivatives as Anticancer Agents

Background: Cancer is the world's second leading cause of death, accounting for an estimate of more than 10 million deaths annually. The most common type of cancers in women are breast, endometrial, cervical, ovarian, colorectal, lung, and skin cancers.Among these, breast cancer is the most common in women of all ages. Human epidermal growth factor receptor 2 breast cancer is widely seen in women which test positive for the protein HER2. This protein is present in one-fifth of every breast cancer cell, which promotes the growth of cancer cells. There are several compounds available for the treatment of HER2 breast cancer in the market with varying promise in their efficacy and safety on HER2 treatment. Objective: To design synthesis and evaluation of core scaffold pyrazolone fused thiazolidinone derivatives as anticancer agents. Methods: In this study, the core scaffold pyrazolone fused thiazolidinone derivatives were designed, synthesized, and analyzed for the anticancer activity using breast carcinoma cell line (MCF-7), against the standard drug Doxorubicin. Results: Many thiazoles, fused thiazole, and pyrazole derivatives have been found to have anticancer and other properties. In this study, the compound 1-phenyl-3-methyl-5-pyrazolones was allowed to react with diverse benzoyl chloride as well as primary amine derivatives and transformed into 'A series of Pyrazolone fused Thiazolidinone derivatives 4A1-4A10 and 4B1- 4B10. Computational studies by Schrodinger Glide XP using the Protein 3RCD which act on the human epidermal growth factor receptor was performed on the selected scheme initially and further from the docked score data the synthesis of pyrazolone fused thiazolidinone was performed. Conclusion: Among the compounds synthesized, five compounds (4A6 - 3.4 kcal/mol, 4B4 - 3.0 kcal/mol, 4A3 - 2.2 kcal/mol, 4B2 - 1.6 kcal/mol, and 4A9 - 1.3 kcal/mol) shown promising binding affinities against epidermal growth factor receptor kinase. The cytotoxic potential of the compounds was examined using a breast carcinoma cell line (MCF-7), which shown cytotoxicity close to Doxorubicin (standard drug). Our findings are an important step forward in the development of novel anticancer agents.

Automated summary

Breast cancer is among the most common types of cancer in women, with HER2-positive breast cancer being widely seen and requiring effective treatment. In this study, novel core scaffold pyrazolone fused thiazolidinone derivatives were synthesized and showed promising anticancer activity in vitro experiments.