# Synthesis, characterization, molecular docking and in vitro anti-arthritic activity of some novel spiro [1,3,4] thiadiazole derivatives based on thioxoacetamides

## TL;DR

Researchers synthesized new spirothiadiazole compounds and found some to be more effective than indomethacin in treating arthritis.

## Contribution

Novel spiro[1,3,4]thiadiazole derivatives with superior anti-arthritic activity compared to standard drugs.

## Key findings

- Compound 9a showed the highest anti-arthritic activity with an IC₅₀ of 29.6 µg/mL.
- Molecular docking revealed strong COX-2 binding affinities for compounds 9a, 10a, and 6a.
- DFT studies confirmed favorable electronic properties comparable to indomethacin.

## Abstract

A new series of spiro[1,3,4]thiadiazole derivatives based on thioxoacetamides were synthesized, characterized, and evaluated for anti-arthritic potential. The structures of all compounds (2a–12a) were confirmed using IR, NMR, and elemental analysis. In vitro anti-arthritic activity was assessed via protein denaturation inhibition and RBC membrane stabilization assays. Compounds 9a, 10a, 6a, 6b, 6c, and 6d showed superior activity compared to the standard drug indomethacin, with 9a being the most potent (IC₅₀ = 29.6 µg/mL for protein denaturation). Molecular docking against COX-2 (PDB: 5IKT) revealed strong binding affinities, especially for 9a (− 8.59 kcal/mol), 10a (− 8.45 kcal/mol), and 6a (− 8.05 kcal/mol). DFT studies indicated favorable electronic properties comparable to indomethacin. These results highlight the promising anti-arthritic potential of the synthesized spirothiadiazole derivatives.

The online version contains supplementary material available at 10.1186/s13065-026-01745-w.