# Synthesis and Biological Evaluation of Novel Thiadiazole Derivatives as Antiplatelet Agents

## TL;DR

Researchers created new thiadiazole compounds that show strong antiplatelet activity, with one compound showing particular promise as a potential drug for inhibiting platelet aggregation.

## Contribution

The study introduces novel thiadiazole derivatives with potent antiplatelet activity and identifies a promising lead compound for P2Y12 inhibition.

## Key findings

- Compound 3b inhibited ADP-induced platelet aggregation with an IC50 of 39 ± 11 µM.
- Molecular docking showed hydrogen bonding and hydrophobic interactions of compound 3b with the P2Y12 receptor.
- The compounds show potential as lead molecules for developing P2Y12 inhibitors.

## Abstract

A novel series of thiadiazole compounds was synthesized through the reaction of thiosemicarbazone intermediates with 2, 3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The antiplatelet activity of the synthesized compounds was evaluated using an aggregation test with adenosine diphosphate (ADP) and arachidonic acid (AA) as platelet aggregation inducers. Among the synthesized analogs, compound 3b exhibited the most potent inhibition of platelet aggregation induced by ADP (half maximal inhibitory concentration [IC50] = 39 ± 11 µM). Molecular docking studies of 3b revealed hydrogen bonds between the nitrogen of the thiadiazole ring and Lys280. The tolyl ring exhibited hydrophobic interactions with Tyr105, similar to the antagonist co-crystallized with P2Y12 (PDB ID: 4NTJ). These compounds have the potential to serve as lead molecules for designing P2Y12 inhibitors.