Synthesis and Biological Evaluation of Novel Isoxazole-Amide Analogues as Anticancer and Antioxidant Agents

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Oncology

Background:

• Cancer is a leading global cause of mortality, necessitating the development of novel anticarcinogenic agents with reduced side effects.
• Isoxazole-carboxamide derivatives represent a class of compounds with potential therapeutic applications.

Purpose of the Study:

• To synthesize and evaluate a series of isoxazole-carboxamide derivatives for their cytotoxic and antioxidant activities.
• To identify lead compounds for potential anticancer drug development.

Main Methods:

• Synthesis of isoxazole-carboxamide derivatives (compounds 2a-2g).
• Evaluation of cytotoxic activity against breast (MCF-7), cervical (HeLa), and liver (Hep3B) cancer cell lines using half-maximal inhibitory concentration (IC50) assays.
• Assessment of antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay.

Main Results:

• Compounds 2d and 2e exhibited potent activity against Hep3B cells (IC50 ~23 μg/ml) and 2d against HeLa cells (IC50 15.48 μg/ml).
• Compound 2a showed the highest activity against MCF-7 cells (IC50 39.80 μg/ml).
• Compounds 2d and 2e induced G2/M phase arrest, reduced necrosis, and promoted apoptosis in Hep3B cells, similar to doxorubicin. Compound 2a was the most potent antioxidant (IC50 7.8 ± 1.21 μg/ml).

Conclusions:

• Isoxazole-carboxamide derivatives 2d and 2e demonstrate significant anticancer potential, particularly against liver and cervical cancer.
• Compound 2a exhibits promising antioxidant activity, suggesting dual therapeutic potential.
• These findings support further investigation of these derivatives as novel therapeutic agents for cancer treatment.