3-Oxo-γ-costic acid fungal-transformation generates eudesmane sesquiterpenes with in vitro tumor-inhibitory activity

Mohamed-Elamir F Hegazy; Ahmed A El-Beih; Ahmed R Hamed; Abeer A Abd El Aty; Naglaa S Mohamed; Paul W Paré

doi:10.1016/j.bmcl.2017.06.057

3-Oxo-γ-costic acid fungal-transformation generates eudesmane sesquiterpenes with in vitro tumor-inhibitory activity

Bioorg Med Chem Lett. 2017 Aug 15;27(16):3825-3828. doi: 10.1016/j.bmcl.2017.06.057. Epub 2017 Jun 23.

Authors

Mohamed-Elamir F Hegazy¹, Ahmed A El-Beih², Ahmed R Hamed³, Abeer A Abd El Aty², Naglaa S Mohamed⁴, Paul W Paré⁵

Affiliations

¹ Phytochemistry Department, National Research Centre, El-Tahrir Street, Dokki, Giza 12622, Egypt.
² Chemistry of Natural & Microbial Products, National Research Centre, El-Tahrir Street, Dokki, Giza 12622, Egypt.
³ Phytochemistry Department, National Research Centre, El-Tahrir Street, Dokki, Giza 12622, Egypt; Biology Unit, Central Laboratory for Pharmaceutical and Drug Industries Research Division, Egypt.
⁴ Chemistry Department, Faculty of Science, Aswan University, Aswan, Egypt.
⁵ Department of Chemistry, Texas Tech University, Lubbock, TX 79409, USA. Electronic address: Paul.Pare@ttu.edu.

PMID: 28676273
DOI: 10.1016/j.bmcl.2017.06.057

Abstract

While select eudesmane sesquiterpenes exhibit anti-neoplastic activity, tumor-inhibition for costic-acids has not been established. Here biological activity of 3-oxo-γ-costic acid (1), previously isolated from Chiliadenus montanus, as well as new sesquiterpenes (2-5) and the known derivative, 3-oxoeudesma-1,4,11(13)-trien-7-1061αH-l2-oic acid (6), all produced from 1 by the fungus Athelia rolfsii, are reported. Structures were elucidated using MS and NMR spectroscopy with activity-screening utilizing human colon- and lung-tumor lines, Caco-2 and A549 respectively. Compound 1 exhibited anti-proliferative activity against Caco-2 (IC₅₀ 39µM) and 2 was active against A549 (IC₅₀ 74µM) suggesting therapeutic potential for the original substrate and a bio-transformed product.

Keywords: 3-Oxo-γ-costic acid; Athelia rolfsii; Chiliadenus montanus; Fungal transformation; Tumor inhibition activity.

Publication types

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

MeSH terms

Antineoplastic Agents / chemistry
Antineoplastic Agents / isolation & purification
Antineoplastic Agents / pharmacology*
Basidiomycota / chemistry*
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Molecular Structure
Sesquiterpenes, Eudesmane / chemistry
Sesquiterpenes, Eudesmane / isolation & purification
Sesquiterpenes, Eudesmane / pharmacology*
Structure-Activity Relationship

Substances

3-oxo-gamma-costic acid
Antineoplastic Agents
Sesquiterpenes, Eudesmane