Design, synthesis, and antitumor activity evaluation of novel acyl sulfonamide spirodienones

Chen Chen; Yang Luo; Honglu Yin; Qiu Zhong; Shilong Zheng; Rui Liu; Chong Zhao; Guangdi Wang; Ling He

doi:10.1016/j.bmc.2022.116626

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. Epub 2022 Jan 11.

Authors

Chen Chen¹, Yang Luo¹, Honglu Yin¹, Qiu Zhong², Shilong Zheng³, Rui Liu⁴, Chong Zhao⁴, Guangdi Wang⁵, Ling He⁶

Affiliations

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: qzhong@xula.edu.
³ Department of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USA. Electronic address: szheng@xula.edu.
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: gwang@xula.edu.
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: heling2012@scu.edu.cn.

Abstract

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.

Keywords: Acyl sulfonamides spirodienone; Anti-proliferation; Apoptosis; MMP2 inhibitor.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents* / pharmacology
Apoptosis
Cell Line, Tumor
Cell Proliferation
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Mice
Molecular Structure
Structure-Activity Relationship
Sulfonamides* / pharmacology

Substances

Antineoplastic Agents
Sulfonamides

Grants and funding

U54 MD007595/MD/NIMHD NIH HHS/United States