# Exploring the Anticancer Properties of 1,2,3-Triazole-Substituted Andrographolide Derivatives

## TL;DR

Researchers synthesized and tested new andrographolide derivatives with triazole groups, finding some to be effective at stopping cancer cell growth and inducing cell death.

## Contribution

The study introduces novel triazole-substituted andrographolide derivatives with enhanced anticancer activity and explores their mechanisms.

## Key findings

- Compounds 9, 14, 16, and 17 showed improved antiproliferative activity compared to the parent compound.
- Derivative 12 induced G2/M cell cycle arrest and apoptosis in PANC-1 cells.
- Compound 12 reduced cell migration and synergized with 5-fluorouracil in pancreatic cancer cells.

## Abstract

Background/Objectives: The search for new anticancer agents from natural sources remains a key strategy in drug discovery. This study aimed to synthesize and evaluate novel triazole derivatives of the diterpenic lactone andrographolide for their antiproliferative activity against various cancer cell lines. Methods: Twenty-two new triazole derivatives (5–26), of the triacetyl derivative (2) of the diterpenic lactone andrographolide (1), were synthesized via the azide-alkyne “click reaction”. The antiproliferative effects of compounds 1–26 were evaluated using the sulforhodamine B assay against a panel of cancer cell lines and a non-tumorigenic colon cell line. A representative compound, triazole derivative 12, was further evaluated in human pancreatic ductal adenocarcinoma (PANC-1) cells for its effects on the cell cycle, apoptosis, migration, and drug synergy with 5-fluorouracil. Results: Several compounds, specifically, 9, 14, 16, and 17, bearing a phenyl moiety, exhibited improved antiproliferative activity compared to the parental compound 1. Derivative 12, selected for further investigation, induced G2/M cell cycle arrest and apoptosis in a concentration-dependent manner. Additionally, this compound significantly reduced cell migration and demonstrated synergistic effects with 5-fluorouracil in PANC-1 cells. Conclusions: The synthesized andrographolide-based triazole derivatives, particularly compound 12, showed promising antiproliferative activity and mechanisms relevant to cancer therapy. These findings support their potential as lead compounds for further development in anticancer research.