Triple-negative breast cancer (TNBC) and prostate cancer are aggressive and hard to treat due to limited targeted therapies. This study aims to develop new compounds that show strong anticancer activity and selectivity to cancer cells more than normal cells. Their ability to induce apoptosis and interact with DNA topoisomerase II makes them promising candidates for future cancer drugs. The research was conducted by Vipan Kumar, Department of Chemistry, Guru Nanak Dev University, Punjab, India, and colleagues.
The team designed and developed triazole-tethered bisnaphthalimide-isatin hybrids using copper-promoted azide-alkyne cycloaddition, a reliable and efficient “click chemistry” technique. Each synthesized molecule connects a bisnaphthalimide unit to an isatin core through a 1,2,3-triazole ring. These compounds were tested against TNBC (MDA-MB-231) and prostate cancer (DU-145) cell lines, and the most active candidates underwent further evaluation for their ability to induce apoptosis via caspase assays.
The results showed a potent activity against MDA-MB-231 and DU-145 cell lines, with IC₅₀ values of 4.4 μM and 3.3 μM, respectively. It performed comparably to standard drugs like cisplatin and 5-fluorouracil and had good selectivity indices (2.07–2.76) against normal cells. Molecular docking studies also revealed strong interactions with DNA topoisomerase II, with a notable docking score of –4.894, comparable to the standard anticancer drug doxorubicin.
These hybrids could lead to new anticancer drugs that are more selective and effective, especially for hard-to-treat cancers like TNBC. Future work may involve optimizing these compounds, testing them in animal models, and exploring their potential in combination therapies.
- Design, Synthesis, and Antiproliferative and Apoptotic Assessment of Triazole-Tethered Bisnaphthalimide-Isatin Hybrids on Triple-Negative Breast and Prostate Cancers
Preeti, Asif Raza, Garima Arora, Amit Anand, Arun K. Sharma, Vipan Kumar
ChemMedChem 2025
https://doi.org/10.1002/cmdc.202500415
