Biotransformation of medicarpin from homopterocarpin by Aspergillus niger and its biological characterization

Abstract

The objective of this study was to convert homopterocarpin derived from Pterocarpus macrocarpus Kurz. heartwood to medicarpin using Aspergillus niger (strain UI X-172) and assess its antioxidant, antiplasmodial, and anticancer activities in silico and in vitro. This study highlighted biotransformation of homopterocarpin to medicarpin via demethylation. Medicarpin demonstrated antioxidant activity against 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS, IC₅₀ = 0.61 ± 0.05 µg/mL) and 1,1-diphenyl-2-picrylhydrazyl (DPPH, IC₅₀ = 7.50 ± 1.6 µg/mL), antiplasmodial activity against the Plasmodium falciparum strain 3D7 (IC₅₀ = 0.45 ± 0.35 µg/mL), and anticancer efficacy against a hepatocyte-derived carcinoma cell line (Huh7it-1 cells, IC₅₀ = 34.32 ± 5.56 µg/mL). Medicarpin also showed favorable antioxidant, antiplasmodial, and anticancer properties in silico with a binding affinity lower than commercial drugs. These results highlight the green synthesis of medicarpin by microbial transformation using A. niger, which demonstrates promising in vitro and computational activity, however, further studies are required for clinical development.

Keywords: Aspergillus Niger; Biological properties; Biotransformation; Homopterocarpin; Medicarpin.

Fig. 1

Chromatogram profile of the biotransformation culture of homopterocarpin from Pterocarpus macrocarpus Kurz. heartwood by Aspergillus niger. (A) First day of culture, (B) Third day of culture, (C) Fifth day of culture, (D) Seventh day of culture. (1) Glycerine; (2) 4 H-Pyran-4-one,2,3-dihydro-3,5-dihydroxy-6-methyl-; (3) 6-Isopropenyl-4,8a-dimethyl-1,2,3,5,6,7,8,8a-octahy-dronaphthalen-2-ol; (4) 9-Octadecenamide, (Z)-; (5) Medicarpin ((6aR,11aR)-9-methoxy-6a,11a-dihydro-6H-[1]benzofuro[3,2-c]chromen-3-ol).

Fig. 2

Structures of homopterocarpin (1) and medicarpin (2).

Fig. 3

Chromatogram profile of medicarpin. (A) TLC Chromatogram (A1. Homopterocarpin; A2. Biotransforntation extract). (B) GC-MS chromatogram (B1. medicarpin library spectra with retention time; B2. medicarpin (sample) of spectra) (C) NMR Chromatogram (C1. ^HNMR chromatogram; C2. ^CNMR chromatogram).

Fig. 4

Visualization of ligand-protein complexes from docking simulations and molecular interaction as antioxidant candidates. (A1) Medicarpin-Cat, (A2) Homopterocarpin-Cat, (B1) Medicarpin-SOD1, (B2) Homopterocarpin-Cat, Cat  Catalase, and SOD1  Superoxide dismutase 1.

Fig. 5

Visualization of ligand-protein complexes from docking simulations and molecular interaction as anticancer candidates. (A1) Medicarpin-EGFR, (A2) Homopterocarpin-EGFR, (B1) Medicarpin-PDGFR, (B2) Homopterocarpin-PDGFR, (C1) Medicarpin-VEGFR, (C2) Homopterocarpin-VEGFR, (D1) Medicarpin-HER2, (D2) Homopterocarpin-HER2, EGFR = epidermal growth factor receptor, PDGFR = Platelet-derived growth factor receptor, VEGFR = Vascular Endothelial Growth Factor Receptor, and HER2 = human epidermal growth factor receptor 2.

Fig. 6

Visualization of ligand-protein complexes from docking simulations and molecular interaction as antiplasmodial candidate (A1) Medicarpin-PfPMV, (A2) Homopterocarpin-PfPMV, (B1) Medicarpin-PfLDH, (B2) Homopterocarpin-PfLDH.

Fig. 7

Graph of RMSF values ​​from the molecular dynamic simulation results. (A1) Medicarpin-Cat, (A2) Homopterocarpin-Cat, (B1) Medicarpin-SOD1, (B2) Homopterocarpin-SOD1, (C1) Medicarpin-EGFR, (C2) Homopterocarpin-EGFR, (D1) Medicarpin-VEGFR, (D2) Homopterocarpin-VEGFR, (E1) Medicarpin-PDGFR, (E2) Homopterocarpin-PDGFR, (F1) Medicarpin-HER2, (F2) Homopterocarpin-HER2, (G1) Medicarpin-PfPMV, (G2) Homopterocarpin-PfPMV, (H1) Medicarpin-PfLDH, (H2) Homopterocarpin-PfLDH, Cat = Catalase, SOD1 = Superoxide dismutase 1, PDGFR = Platelet-derived growth factor receptor, VEGFR = Vascular Endothelial Growth Factor Receptor, HER2 = human epidermal growth factor receptor 2, PfPMV = P. falciparum plasmepsin V, and PfLDH = P. falciparum lactate dehydrogenase.