Synthesis of 14-deoxy-11,12-didehydroandrographolide analogues as potential cytotoxic agents for cholangiocarcinoma

Sudarat Sombut; Rada Bunthawong; Uthaiwan Sirion; Teerapich Kasemsuk; Pawinee Piyachaturawat; Kanoknetr Suksen; Apichart Suksamrarn; Rungnapha Saeeng

doi:10.1016/j.bmcl.2017.10.063

Synthesis of 14-deoxy-11,12-didehydroandrographolide analogues as potential cytotoxic agents for cholangiocarcinoma

Bioorg Med Chem Lett. 2017 Dec 1;27(23):5139-5143. doi: 10.1016/j.bmcl.2017.10.063. Epub 2017 Oct 30.

Authors

Sudarat Sombut¹, Rada Bunthawong¹, Uthaiwan Sirion¹, Teerapich Kasemsuk², Pawinee Piyachaturawat³, Kanoknetr Suksen³, 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, Faculty of Science and Technology, Rambhai Barni Rajabhat University, Chanthaburi 22000, 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. Electronic address: [email protected].

PMID: 29097170
DOI: 10.1016/j.bmcl.2017.10.063

Abstract

A series of 14-deoxy-11,12-didehydroandrographolide analogues were synthesized from naturally occurring andrographolide and their cytotoxicity evaluated against nine cancer cell lines including cholangiocarcinoma. Analogues 5a and 5b exhibited the most potent cytotoxicity with ED₅₀s of 3.37 and 3.08 μM on KKU-M213 cell lines and 2.93 and 3.27 μM on KKU-100 cell lines, respectively. Selective cytotoxicity on cholangiocarcinoma cell lines identified in this study highlight the importance of structural modification in the development of drugs for this cancer.

Keywords: 12-didehydroandrographolide; 14-Deoxy-11; Andrographis paniculata Nees; Cholangiocarcinoma; Cytotoxic activity.

Publication types

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

MeSH terms

Andrographis / chemistry
Andrographis / metabolism
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / pharmacology
Bile Duct Neoplasms / metabolism
Bile Duct Neoplasms / pathology
Cell Line, Tumor
Cell Survival / drug effects
Cholangiocarcinoma / metabolism
Cholangiocarcinoma / pathology
Diterpenes / chemistry*
Diterpenes / pharmacology
Drug Screening Assays, Antitumor
Humans
Plant Extracts / chemistry
Structure-Activity Relationship

Substances

14-deoxy-11,12-didehydroandrographolide
Antineoplastic Agents
Diterpenes
Plant Extracts