Design, synthesis, and antitumor activity evaluation of novel acyl sulfonamide spirodienones
- Bioorg Med Chem. 2022 Apr 15;60:116626. doi: 10.1016/j.bmc.2022.116626.
- 1. Key Laboratory of Drug-Targeting and Drug-Delivery Systems of the Ministry of Education, Department of Medicinal Chemistry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
- 2. Department of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USA. Electronic address: [email protected].
- 3. Department of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USA. Electronic address: [email protected].
- 4. Laboratory of Gastroenterology and Hepatology, West China Hospital, Sichuan University, No. 1, 4th Keyuan Road, Chengdu 610041, China.
- 5. Department of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USA. Electronic address: [email protected].
- 6. Key Laboratory of Drug-Targeting and Drug-Delivery Systems of the Ministry of Education, Department of Medicinal Chemistry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. Electronic address: [email protected].
Based on the promising results of benzenesulfonamide spirodienones as antineoplastic agents, we have designed and synthesized a series of novel acyl sulfonamides spirodienone for antineoplastic evaluation. Of these, compound 4a exhibited remarkable in vitro antiproliferative activity by arresting the cell cycle and inducing Apoptosis of MDA-MB-231 cells. Acute toxicity study has demonstrated 4a at 100 mg/kg dose caused no obvious toxicity to the major organs of mice. Moreover, compound 4a suppressed the growth of murine 4T1 tumor in vivo. Preliminary enzyme assay showed that 4a was a potential MMP2 inhibitor for Cancer therapy. In all, these results indicate that compound 4a may be a lead compound for the development of Anticancer agents.