Biotransformation of bioactive compounds from sonchus arvensis L. and pterocarpus macrocarpus kurz. by Aspergillus niger

Abstract

In recent years, microbial transformation is progressing significantly from a limited interest in the highly active area in green chemistry, including the preparation of pharmaceutical compounds. Many biotransformation studies have been found in a variety of analogous compounds and exhibited more potent pharmacological activities. The objectives of this study are (i) to isolate and identify bioactive compounds from Sonchus arvensis L. and Pterocarpus macrocarpus Kurz., (ii) to transform selected bioactive compounds from S. arvensis L. and P. macrocarpus Kurz. by Aspergillus niger, (iii) to determine bioactivities of selected bioactive compounds from Sonchus arvensis L. and Pterocarpus macrocarpus Kurz. before and after biotransformation. The extracts from S. arvensis L. leaf and P. macrocarpus Kurz. heartwood prepared by successive maceration with n-hexane, ethyl acetate, and ethanol and then subjected to quantitative phytochemical analysis using standard methods. Isolated compound was evaluated by thin-layer chromatography (TLC), gas chromatography-mass spectrophotometry (GC-MS), Fourier transform infrared (FITR) spectroscopy, and nuclear magnetic resonance (NMR). Taraxasterol (S. arvensis L. leaf) and homopterocarpin (P. macrocarpus Kurz. heartwood) were transformed in soy bean meal (SBM) medium by Aspergillus niger. The Peter's 4-day suppressive test model with P. berghei-infected mice was used to evaluate the in vivo antiplasmodial activities, hepatoprotective, nephroprotective, and immunomodulatory (ethyl acetate extract of S. arvensis L.). For all natural products were conducted the in vitro antimalarial activity assay against Plasmodium falciparum 3D7 strain, in silico anti-SARS-CoV-2, in vitro antioxidant against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and antimicrobial disc diffusion method against Candida albicans, Bacillus subtilis, Escherichia coli, and Staphylococcus aureus) activities were established. Hepatocyte-derived cellular carcinoma cell line (Huh7it-1cells) was used for an in vitro cytotoxicity and anticancer assay [3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; MTT]. The n-hexane, ethyl acetate, and ethanolic extract exhibited a good activity on in vitro antiplasmodial activity of S. arvensis L. leaf, with IC50 values were 5.119±3.27, 2.916±2.34, and 8.026±1.23 µg/mL, respectively. Each extract also exhibited high antioxidants with low cytotoxic effects. Furthermore, the ethyl acetate extract showed in vivo antiplasmodial activity with ED50 = 46.31±9.36 mg/kg, body weight, as well as hepatoprotective, nephroprotective, and immunomodulatory activities in mice infected with P. berghei. The ethyl acetate, ethanol, and n-hexane extracts of P. macrocarpus Kurz., as well as homopterocarpin, exhibited antiplasmodial activity at 1.78, 2.21, 7.11, and 0.52 µg/ml, respectively, against P. falciparum 3D7 with low toxicity. A compound identified by GC-MS showed in silico anti-SARS-CoV-2 binding affinity with stigmasterol and SARS-CoV-2 helicase of −8.2 kcal/mol. All extracts exhibited antioxidant activity against DPPH and ABTS. They also demonstrated antimicrobial activity against B. subtilis, the ethanol and ethyl acetate extracts against E. coli and C. albicans, and the ethanol extract against S. aureus. GC-MS analysis of fraction of S. arvensis L. n-hexane extract revealed ß-amyrin, lupeol, α-amyrin, betulin, and taraxasterol. The in silico anti-SARS-CoV-2 assay showed that they were predicted as effective antiviral candidates by having the ability to act as inhibitors of SARS-CoV-2 protein activity. Therefore, the molecular dynamic analysis data strengthen the notion that the interactions resulting from the five compounds of n-hexane fractions of S. arvensis L. leaves were stable and predicted to be effective antiviral candidates by having the ability to act as inhibitors of SARS-CoV-2 protein activity. Biotransformation of homopterocarpin was succeed by Aspergillus niger. Two compounds have been isolated from biotransformation culture extract. They are 6-isopropenyl-4,8a-dimethyl-1,2,3,5,6,7,8,8a-octahydro-naphthalene-2-ol (major compound) and medicarpin. Medicarpin could be predicted transformed from homopterocarpin by demethylation. It showed in vitro antioxidant activity against DPPH (IC50 = 7.49±1.7 µg/mL) and 2,2-azino-bis ABTS (IC50 = 0.61±0.4 µg/mL), in vitro antiplasmodial (0.414 µg/mL), and in vitro anticancer (IC50 =34.96 µg/mL). Overall, this study collectively advances our knowledge of important drug discovery from natural products with a major impact in improving of natural product isolation and biotransformation from Thai and Indonesian medicinal plant and elsewhere around the world.