Synthesis, cytotoxicity, and in vivo antitumor activity study of parthenolide semicarbazones and thiosemicarbazones

Xinxin Jia; Qi Liu; Shiyi Wang; Binglin Zeng; Guohua Du; Chen Zhang; Yan Li

doi:10.1016/j.bmc.2020.115557

Synthesis, cytotoxicity, and in vivo antitumor activity study of parthenolide semicarbazones and thiosemicarbazones

Bioorg Med Chem. 2020 Jul 1;28(13):115557. doi: 10.1016/j.bmc.2020.115557. Epub 2020 May 19.

Authors

Xinxin Jia¹, Qi Liu¹, Shiyi Wang¹, Binglin Zeng², Guohua Du², Chen Zhang³, Yan Li⁴

Affiliations

¹ School of Chemical Engineering, Beijing Institute of Petrochemical Technology, Beijing 102617, PR China.
² State Key Laboratory of Bioactive Substance and Function of Natural Medicines and Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
³ School of Chemical Engineering, Beijing Institute of Petrochemical Technology, Beijing 102617, PR China; Beijing Key Laboratory of Enze Biomass Fine Chemicals, Beijing Institute of Petrochemical Technology, Beijing 102617, PR China. Electronic address: zhangc@bipt.edu.cn.
⁴ State Key Laboratory of Bioactive Substance and Function of Natural Medicines and Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China. Electronic address: liyanxiao@imm.ac.cn.

PMID: 32546298
DOI: 10.1016/j.bmc.2020.115557

Abstract

Parthenolide is an important sesquiterpene lactone with potent anticancer activities. In order to further improve its biological activity, a series of parthenolide semicarbazone or thiosemicarbazone derivatives was synthesized and evaluated for their anticancer activity. Derivatives were tested in vitro against 5 human tumor cell lines, and many of these showed higher cytotoxicity than parthenolide. Five compounds were further studied for their antitumor activity in mice. The in vivo result indicated that compound 4d showed both promising antitumor activity against mice colon tumor and small side effects on immune systems. The cell apoptosis and cell cycle distribution of compound 4d were also studied. Molecular docking studies revealed multiple interactions between 4d and NF-κB. Our findings demonstrate the potential of semicarbazones as a promising type of compounds with anticancer activity.

Keywords: Anticancer; In vivo; Parthenolide; Semicarbazone.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / pharmacology
Apoptosis / drug effects
Carbamates / chemistry
Cell Line, Tumor
Cell Survival / drug effects
Drug Screening Assays, Antitumor
Humans
Male
Mice
Mice, Inbred C57BL
Molecular Docking Simulation
NF-kappa B / metabolism
Neoplasms, Experimental
Semicarbazones / chemical synthesis*
Semicarbazones / pharmacology
Sesquiterpenes / chemistry*
Structure-Activity Relationship
Thiosemicarbazones / chemical synthesis*
Thiosemicarbazones / pharmacology

Substances

Antineoplastic Agents
Carbamates
NF-kappa B
Semicarbazones
Sesquiterpenes
Thiosemicarbazones
parthenolide