Design and synthesis of C-12 dithiocarbamate andrographolide analogues as an anticancer agent

Patcharee Arsakhant; Uthaiwan Sirion; Arthit Chairoungdua; Kanoknetr Suksen; Pawinee Piyachaturawat; Apichart Suksamrarn; Rungnapha Saeeng

doi:10.1016/j.bmcl.2020.127263

Design and synthesis of C-12 dithiocarbamate andrographolide analogues as an anticancer agent

Bioorg Med Chem Lett. 2020 Jul 15;30(14):127263. doi: 10.1016/j.bmcl.2020.127263. Epub 2020 May 13.

Authors

Patcharee Arsakhant¹, Uthaiwan Sirion², Arthit Chairoungdua³, Kanoknetr Suksen³, Pawinee Piyachaturawat³, Apichart Suksamrarn⁴, Rungnapha Saeeng⁵

Affiliations

¹ Department of Chemistry and Center for Innovation in Chemistry, Faculty of Science, Burapha University, Chonburi 20131, Thailand.
² Department of Chemistry and Center for Innovation in Chemistry, Faculty of Science, Burapha University, Chonburi 20131, Thailand; The Research Unit in Synthetic Compounds and Synthetic Analogues from Natural Product for Drug Discovery (RSND), Burapha University, Chonburi 20131, Thailand.
³ Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
⁴ Department of Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand.
⁵ Department of Chemistry and Center for Innovation in Chemistry, Faculty of Science, Burapha University, Chonburi 20131, Thailand; The Research Unit in Synthetic Compounds and Synthetic Analogues from Natural Product for Drug Discovery (RSND), Burapha University, Chonburi 20131, Thailand. Electronic address: rungnaph@buu.ac.th.

PMID: 32527561
DOI: 10.1016/j.bmcl.2020.127263

Abstract

A series of 21 new analogues of C-12 dithiocarbamate andrographolide was designed and synthesized from natural andrographolide isolated from a common Thai plant, Andrographis paniculata. The reaction used to manipulate the andrographolide scaffold was conducted in one pot under mild reaction conditions. This avoided toxic catalysts and gave nearly quantitative yields of new analogues, generally without by-products and can be easily scaled -up for industrial processing. All new analogues were evaluated against nine cancer cell lines, some analogues exhibited greater selective cytotoxic activity to MCF-7 cancer cell than that of the parent andrographolide and cancer drugs.

Keywords: Andrographis paniculata; Andrographolide; Cytotoxic activity; Dithiocarbamate.

Publication types

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

MeSH terms

Andrographis / chemistry*
Antineoplastic Agents, Phytogenic / chemical synthesis
Antineoplastic Agents, Phytogenic / chemistry
Antineoplastic Agents, Phytogenic / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Diterpenes / chemical synthesis
Diterpenes / chemistry
Diterpenes / pharmacology*
Dose-Response Relationship, Drug
Drug Design*
Drug Screening Assays, Antitumor
Humans
Molecular Structure
Structure-Activity Relationship

Substances

Antineoplastic Agents, Phytogenic
Diterpenes
andrographolide