Synthesis and Biological Evaluation of Thio-Derivatives of 2-Hydroxy-1,4-Naphthoquinone (Lawsone) as Novel Antiplatelet Agents

Abstract

We designed and synthesized in water, using conventional heating and microwave irradiation, new thio-derivatives of 2-hydroxy-1,4-naphthoquinone, a naturally occurring pigment known as lawsone or hennotannic acid, thus improving their antiplatelet activity with relevance to their potential future use in thrombus formation treatment. The structure-activity relationship showed that the thiophenyl moiety enhances the antiplatelet activity. Moreover, the position and nature of the substituent at the phenyl ring have a key effect on the observed biological activity. Compound 4 (2-((4-bromophenyl)thio)-3-hydroxynaphthalene-1,4-dione) was the most active derivative, presenting IC 50 values for platelet aggregation inhibition of 15.03 ± 1.52 µM for TRAP-6, and 5.58 ± 1.01 µM for collagen. Importantly, no cytotoxicity was observed. Finally, we discussed the structure-activity relationships of these new lawsone thio-derivatives on inhibition of TRAP-6-and collagen-induced platelet aggregation.

In Vitro Effect of Mitochondria-Targeted Triphenylphosphonium-Based Compounds (Honokiol, Lonidamine, and Atovaquone) on the Platelet Function and Cytotoxic Activity

“…Briefly, whole blood was obtained with an acid-citrate-dextrose (ACD) solution (proportion 4:1 v/v) and centrifuged at room temperature for 12 min × 200 g to collect platelet-rich plasma (PRP). Then, the PRP was centrifuged for 8 min × 900 g. The platelet pellet was suspended in calcium-free Tyrode’s buffer/ACD (proportion: 5:1 v/v) and this was centrifuged again for 8 min × 900 g; then, the platelets were resuspended t in calcium-free Tyrode’s buffer and adjusted to the assays with a hematological counter (Mindray BC-3000 Plus, Japan) and used within 3 h ( Monroy-Cárdenas et al, 2020 ). The discard of pre-activation of platelets during preparation is shown in Supplementary Figure S1 .…”

An Experimental and Theoretical Study of Dye Properties of Thiophenyl Derivatives of 2-Hydroxy-1,4-naphthoquinone (Lawsone)

“…Compounds 1 – 7 were obtained using an on-water methodology previously described [ 26 ]. 1 H and 13 C NMR spectra were obtained from a spectrometer operating at either 400.13 MHz ( 1 H) or 100.61 MHz ( 13 C) at 300 K. All melting points were uncorrected and were determined using Electrothermal 9100 apparatus (Cole-Parmer, Stone, UK).…”

“…Thus, this study aims to assess the impact of structural modifications on dye characteristics. Lawsone thiophenyl derivatives are easily accessible via a green synthetic methodology and have shown low toxicity in a previous study [ 26 ]. An experimental–theoretical approach was used to carry out a detailed description of the properties of these derivatives as dyes ( Table 1 ), and the potential application in colorimetry and solar cells compared with that of lawsone is discussed.…”

Square-Wave Voltammetric Sensing of Lawsone (2- Hydroxy-1,4-Naphthoquinone) Based on the Enhancement Effect of Cationic Surfactant on Anodically Pretreated Boron-Doped Diamond Electrode

“…All electrochemical experiments were carried out at room temperature using an Autolab PGSTAT128N (Metrohm Autolab B.V., The Netherlands) which was managed by the software GPES 4.9. The counter electrode was platinum wire, the reference electrode was Ag/AgCl electrode and the working electrode was a BDD electrode (3 mm diameter, geometric surface area of 0.07 cm 2 and declared boron doping level of 1000 ppm). Before experiments, the BDD electrode was electrochemically pretreated in an independent electrochemical cell.…”

“…), known as hennotannic acid, is a red-orange dye found in the leaves of the henna plant (Lawsonia inermis) and water hyacinth flower. [1][2][3] Henna extract or its purified compounds exhibit a variety of biological activities such as antimicrobial, cytotoxic, anti-inflammatory, antioxidant, anticancer and analgesic activities. Henna leaves have been used as a cosmetic colorant for centuries and contain a high proportion of lawsone (1.0-1.4%).…”