Biotransformation of abietic acid by fungi and biological evaluation of its metabolites


ÖZŞEN BATUR Ö., KIRAN İ., DAĞ İ., ATLI Ö., AKALIN ÇİFTÇİ G., DEMİRCİ F.

PROCESS BIOCHEMISTRY, vol.52, pp.130-140, 2017 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 52
  • Publication Date: 2017
  • Doi Number: 10.1016/j.procbio.2016.09.022
  • Journal Name: PROCESS BIOCHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.130-140
  • Keywords: Abietic acid, Anticancer activity, Antimicrobial activity, Biotransformation, Cytotoxicity, Genotoxicity, DEHYDROABIETIC ACID, ANTIINFLAMMATORY ACTIVITY, ANTICANCER, HYDROXYLATION, DERIVATIVES, DITERPENES, DRUGS
  • Eskisehir Osmangazi University Affiliated: Yes

Abstract

Biotransformation of abietic acid was carried out initially using 28 different microbial strains. Among the evaluated, Mucor ramannianus produced a known metabolite namely 2 alpha-hydroxy-dehydroabietic acid whereas Neurospora crassa yielded two known metabolites of 7 beta-hydroxy-dehydroabietic and 1 beta-hydroxy-dehydroabietic acids in 12.7, 15.5 and 20.1% yields, respectively. The in vitro antimicrobial activities of the metabolites were evaluated against 19 different pathogenic microorganisms, resulting in moderate inhibitory activity when compared to the standards, with MICs >250 mu g/mL. However, in the in vitro anticancer activity studies, 2 alpha-hydroxy-dehydroabietic acid was found to be the most effective derivative against A549 human lung adenocarcinoma cell line with an IC50 value of 320.8 mu g/mL and SI (Selectivity index) of 156, respectively. Using the same assay and conditions, 7 beta-hydroxy-dehydroabietic was found to be the most effective and selective antiproliferative agent against HepG2 cell line with an IC50 value of 196.6 mu g/mL and SI of 187, respectively. Contrary to the antimicrobial activity, the biotransformation metabolites showed promising results suggesting selective toxicity against specific cancer cell line where the genotoxicity of the same derivatives were in a negligible range. Furthermore, DNA synthesis inhibition of metabolites were more promising in the A549 cell line while apoptotic effects were better in HepG2 cell line. (C) 2016 Elsevier Ltd. All rights reserved.