Conversion of the natural product andrographolide to isoandrographolide acetals leads to improvement in anticancer activity

Identifying the Issue

• Chemotherapy is the most commonly used method to cure cancer since the drug used diffuses into the cancerous cell but it comes with a cost of many side effects
• Side effects such as inflammation, immunosuppression, and digestive tract lining disorders.
• So, there is a need for the development of better anticancer drugs with fewer side effects and higher potency.

Objective of the Research

• To semi-synthesize isoandrographolide acetals from the natural product andrographolide and study their anticancer activity

Who should read this?

Faculty, research scholars and students of Medicinal  and Organic chemistry

Solution

Isoandrographolide  and its eighteen acetals  were synthesized and characterized using ¹H-NMR, ¹³C-NMR, mass spectrometry(HRMS), IR, and UV spectroscopy. The compound (3,19)-3,5-difluorobenzylidene-isoandrographolide was characterized using single-crystal X-ray diffraction also. All the compounds were tested for their anti-cancer activity. The compound (3,19)-4-Bromobenzylidene-isoandrographolide (IC₅₀ 3 μM) was more active than tamoxifen (IC₅₀ 12 μM) against MCF-7 and arrested the cell cycle at G1-Phase and was observed to be inducing apoptosis and loss of mitochondrial membrane potential.

Key Features and Benefits

• Compound (3,19)-4-Bromobenzylidene-isoandrographolide (IC₅₀ 3 μM) was more active than tamoxifen (IC₅₀ 12 μM).
• Isoandrographolide acetals can be further explored as potential anticancer leads

Impact

• Potential as leads in the development of anticancer drug

Team

Nitesh Tamang, Yashwanth Inabathina, Sai Kiran Mavileti, Lakshminath Sripada, Srinivas Nanduri, Nageswara Rao Golakoti and Balasubramanyam Karanam

Title of paper: Bromobenzylidene-isoandrographolide Induces Apoptosis and Causes Loss of Mitochondrial Membrane Potential in MCF-7 Breast Cancer cells

Read Paper Here: https://doi.org/10.1002/slct.202302498

Synthesis, Characterization and anti-cancer activity of isoandrographolide acetals.