Andrology-Open Access
Open Access
ISSN: 2167-0250
+44 1300 500008
ISSN: 2167-0250
+44 1300 500008
Laila A. Jaragh-Alhadad*
In medicinal chemistry, the 1,2,4-triazole scaffold has a wide spectrum of applications. Using this scaffold to synthesize new derivatives as anticancer agents targeting proliferation proteins like HER2 and β-tubulin and delivered by nano-LDL particles to specific sites is an attractive approach. The 1,2,4-triazole derivatives were fully characterized, an x-ray single crystal confirmed the structure of agent 4f and the morphologies were studied to prove the particles’ nano size. The agents were encapsulated into nano-LDL particles, to benefit from the lipid metabolic pathway and the nano-particle size showed an increase after encapsulation. The biological results in the present study showed that 1,2,4-triazole derivatives have anticancer activity toward both breast (MDA468) and prostate (DU145) cancer cell lines. The molecular docking technique was used to predict the potent β-tubulin inhibitor and the scores of eight synthesized compounds were investigated. Biological evaluation and the insilico investigation results were parallel. The results showed that agent 4f was the potent triazole derivative with chlorine substituent that possesses the activity toward both cancer cell lines in the range of 1.23 ± 0.18 and 1.20 ± 0.78 μM, respectively. In the DU145 cell line cancer cell death was through targeting both HER2 receptor and β-tubulin proteins, while in MDA468 the inhibition was through targeting only tubulin as proved in western blot assessment because MDA468 is HER2 negative receptor. In addition, the docking results revealed that the eight agents targeting β-tubulin, specifically agent 4f has an outstanding score of -5.9 kcal/mol compared with doxorubicin (calc. -6.8 kcal/mol). In sum, 1,2,4-triazole derivatives showed potent anticancer activity targeting HER2 receptor protein and β-tubulin cellular protein in one shot.
Published Date: 2025-04-04; Received Date: 2024-02-19