Synthesis and cytotoxic activity of new 7-acetoxy-12-amino-14-deoxy andrographolide analogues

Rada Bunthawong; Uthaiwan Sirion; Arthit Chairoungdua; Kanoknetr Suksen; Pawinee Piyachaturawat; Apichart Suksamrarn; Rungnapha Saeeng

doi:10.1016/j.bmcl.2020.127741

Synthesis and cytotoxic activity of new 7-acetoxy-12-amino-14-deoxy andrographolide analogues

Bioorg Med Chem Lett. 2021 Feb 1:33:127741. doi: 10.1016/j.bmcl.2020.127741. Epub 2020 Dec 13.

Authors

Rada Bunthawong¹, 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, Products 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, Products for Drug Discovery (RSND), Burapha University, Chonburi 20131, Thailand. Electronic address: rungnaph@buu.ac.th.

PMID: 33316411
DOI: 10.1016/j.bmcl.2020.127741

Abstract

Two new series of 19-silylether- and 19-formyl-7-acetyl-12-amino-14-deoxyandrographolide analogues were designed and synthesized from natural andrographolide via key step reactions including allylic hydroxylation, tandem CAE reaction and one pot formylation. Evaluation of their cytotoxicity against eight cancer cells line found 6e exhibited the highest activity on MCF-7 cancer cell (IC₅₀ 2.93) and comparable to the drug elipticin. Replacement of silylether at C-19 with formyl group exhibited selective activity on P-388 cell line. Computational studies revealed the amino group at C-12 and O-acetoxy at C-7 position play significant roles in cytotoxicity against MCF-7 cancer cells. Cytotoxicity of these two series highlights the importance of 12-substituted-14-deoxyandrographolide scaffold and these types of compounds could be employed in future developments against breast cancer.

Keywords: 7-Acetoxy-12-amino-14-deoxyandrographolide derivatives; Andrographis paniculata nees; Andrographolide; Cytotoxic activity.

Publication types

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

MeSH terms

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

Substances

14-deoxyandrographolide
Antineoplastic Agents
Diterpenes