Please cite this article in press as: Ö. Özs ¸ en, et al., Biotransformation of abietic acid by fungi and biological evaluation of its metabolites, Process Biochem (2016), http://dx.doi.org/10.1016/j.procbio.2016.09.022 ARTICLE IN PRESS G Model PRBI-10813; No. of Pages 11 Process Biochemistry xxx (2016) xxx–xxx Contents lists available at ScienceDirect Process Biochemistry journal homepage: www.elsevier.com/locate/procbio Biotransformation of abietic acid by fungi and biological evaluation of its metabolites Özge Özs ¸ en a , ˙ Ismail Kıran a,∗ , ˙ Ilknur Da˘ g b , Özlem Atlı c , Güls ¸ en A. C ¸ iftc ¸ i d , Fatih Demirci e a Department of Chemistry, Eskisehir Osmangazi University, 26480 Eskisehir, Turkey b Vocational Health Services High School, Eskisehir Osmangazi University, 26480, Eskisehir, Turkey c Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir, Turkey d Department of Biochemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir, Turkey e Department of Pharmacognosy, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir, Turkey a r t i c l e i n f o Article history: Received 16 June 2016 Received in revised form 19 September 2016 Accepted 23 September 2016 Available online xxx Keywords: Abietic acid Anticancer activity Antimicrobial activity Biotransformation Cytotoxicity Genotoxicity a b s t r a c t Biotransformation of abietic acid was carried out initially using 28 different microbial strains. Among the evaluated, Mucor ramannianus produced a known metabolite namely 2˛-hydroxy-dehydroabietic acid whereas Neurospora crassa yielded two known metabolites of 7ˇ-hydroxy-dehydroabietic and 1ˇ- 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 g/mL. However, in the in vitro anticancer activity studies, 2˛-hydroxy-dehydroabietic acid was found to be the most effective derivative against A549 human lung adenocarcinoma cell line with an IC 50 value of 320.8 g/mL and SI (Selectivity index) of 156, respectively. Using the same assay and conditions, 7ˇ-hydroxy-dehydroabietic was found to be the most effective and selective antiproliferative agent against HepG2 cell line with an IC 50 value of 196.6 g/mL and SI of 187, respectively. Contrary to the antimicrobial activity, the biotrans- formation 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 syn- thesis inhibition of metabolites were more promising in the A549 cell line while apoptotic effects were better in HepG2 cell line. © 2016 Elsevier Ltd. All rights reserved. 1. Introduction Abietic acid also known as abietinic acid or sylvic acid is a nat- ural compound that occurs widely in trees [1–3]. It belongs to the abietane diterpene group and is the main component of rosin [4–6]. Recent studies have explored diverse biological and pharmaco- logical activities of abietic acid such as antioxidant activity [7,8], anti-inflammatory activity [9–11], cardiovascular activity [2], fibrin modulating and fibrinolytic activity [11], antiacetylcholinesterases activity [8], in vitro testosterone 5˛-reductase inhibitory activity [6], antibacterial activity [7,8,12], antifungal activity [7] and anti- cancer activity [5,9]. Microbial biotransformation is an ecologically and economi- cally viable technology used extensively to modify the structures of various classes of biologically active compounds [13]. It has ∗ Corresponding author. E-mail addresses: ikiran@ogu.edu.tr, ikiran1971@gmail.com ( ˙ I. Kıran). attracted considerable interest in recent decades because it allows not only producing novel compounds not existing in nature but also results in improving pharmacological profiles of natural com- pounds [14]. In this context, the microbiological biotransformation of abietic acid has been carried out by using various fungi. The main reactions observed during microbial biotransformation are hydrox- ylation [1,10,15–23], dehydrogenation [2,19–23], aromatization at C ring [1,16,18–23], carbonyl reduction [1,2] and ketone addition [1,19,21,22]. Considering the previous significant antimicrobial and anti- cancer activities, the present study has been undertaken to obtain abietic acid metabolites through microbial biotransformation and to evaluate the possible antimicrobial, anticancer and cytotoxic activities of its biotransformation metabolites. http://dx.doi.org/10.1016/j.procbio.2016.09.022 1359-5113/© 2016 Elsevier Ltd. All rights reserved.