In this study, we designed and synthesized eight thiophene chalcone derivatives (1a–h) as tyrosinase inhibitors and evaluated their mushroom tyrosinase inhibitory activities. Of these eight compounds, (E)-3-(2,4-dihydroxyphenyl)-1-(thiophen-2-yl)prop-2-en-1-one (1c) showed strong competitive inhibition activity against mushroom tyrosinase with IC₅₀ values of 0.013 μM for tyrosine hydroxylase and 0.93 μM for dopa oxidase. In addition, we used enzyme kinetics study and docking program to further evaluate the inhibitory mechanism of 1c toward tyrosinase. As an underlying mechanism of 1c mediated anti-melanogenic effect, we investigated the inhibitory activity against melanin contents and cellular tyrosinase in B16F10 melanoma cells. As the results, the enzyme kinetics and docking results supports that 1c highly interacts with tyrosinase residues in the tyrosinase active site and it can directly inhibit tyrosinase as competitive inhibitor. In addition, 1c exhibited dose-dependent inhibitory effects in melanin contents and intracellular tyrosinase on α-MSH and IBMX-induced B16F10 cells. Overall, our results suggested that 1c might be considered potent tyrosinase inhibitor for use in the development of therapeutic agents for diseases associated with hyperpigment disorders.

Three aqueous plant extracts (Artemisia capillaris, Portulaca oleracea, and Prunella vulgaris) were selected for the biofabrication of gold nanoparticles. The antioxidant activities (i.e., free radical scavenging activity, total phenolic content, and reducing power) of the extracts and how these activities affected the biofabrication of gold nanoparticles were investigated. P. vulgaris exerted the highest antioxidant activity, followed by A. capillaris and then P. oleracea. P. vulgaris was the most efficient reducing agent in the biofabrication process. Gold nanoparticles biofabricated by P. vulgaris (PV-AuNPs) had a maximum surface plasmon resonance of 530 nm with diverse shapes. High-resolution X-ray diffraction analysis showed that the PV-AuNPs had a face-centered cubic structure. The reaction yield was estimated to be 99.3% by inductively coupled plasma optical emission spectroscopy. The hydrodynamic size was determined to be 45 ± 2 nm with a zeta potential of − 13.99 mV. The PV-AuNPs exerted a dose-dependent antioxidant activity. Remarkably, the highest cytotoxicity of the PV-AuNPs was observed against human colorectal adenocarcinoma cells in the absence of fetal bovine serum, while for human pancreas ductal adenocarcinoma cells, the highest cytotoxicity was observed in the presence of fetal bovine serum. This result demonstrates that P. vulgaris extract was an efficient reducing agent for biofabrication of gold nanoparticles exerting cytotoxicity against cancer cells.