A novel synthetic acanthoic acid analogues and their cytotoxic activity in cholangiocarcinoma cells

Teerapich Kasemsuk; Natthiya Saehlim; Patcharee Arsakhant; Gunya Sittithumcharee; Seiji Okada; Rungnapha Saeeng

doi:10.1016/j.bmc.2020.115886

A novel synthetic acanthoic acid analogues and their cytotoxic activity in cholangiocarcinoma cells

Bioorg Med Chem. 2021 Jan 1:29:115886. doi: 10.1016/j.bmc.2020.115886. Epub 2020 Dec 1.

Authors

Teerapich Kasemsuk¹, Natthiya Saehlim², Patcharee Arsakhant², Gunya Sittithumcharee³, Seiji Okada³, Rungnapha Saeeng⁴

Affiliations

¹ Department of Chemistry, Faculty of Science and Technology, Rambhai Barni Rajabhat University, Chanthaburi 22000, Thailand.
² Department of Chemistry and Center for Innovation in Chemistry, Faculty of Science, Burapha University, Chonburi 20131, Thailand.
³ Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection & Graduate School of Medical Sciences, Kumamoto University, Japan.
⁴ 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: 33290909
DOI: 10.1016/j.bmc.2020.115886

Abstract

A novel series of acanthoic acid analogues containing triazole moiety were synthesized through esterification and CuAAC reaction. Evaluation of their biological activities against four cell lines of cholangiocarcinoma cells showed that 3d exhibited the strongest activity with an IC₅₀ value of 18 µM against KKU-213 cell line, which was 8 fold more potent than acanthoic acid. Interestingly, the triazole ring and nitro group on benzyl ring play very significant role in cytotoxic activity. The computational studies revealed that 3d occupies the binding energy of -12.7 and -10.8 kcal/mol with CDK-2 and EGFR protein kinases, respectively. This result might provide a beginning for the development of acanthoic acid analogues as an anticancer agent.

Keywords: Acanthoic acid; Cholangiocarcinoma; Cytotoxicity; Modification; Triazole.

Publication types

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

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Bile Duct Neoplasms / drug therapy*
Bile Duct Neoplasms / pathology
Cell Line, Tumor
Cell Proliferation / drug effects
Cholangiocarcinoma / drug therapy*
Cholangiocarcinoma / pathology
Diterpenes / chemical synthesis
Diterpenes / chemistry
Diterpenes / pharmacology*
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Models, Molecular
Molecular Structure
Structure-Activity Relationship

Substances

Antineoplastic Agents
Diterpenes
acanthoic acid