Novel 3,19-(N-Phenyl-3-(4-fluorophenyl)-pyrazole) Acetal of Andrographolide Promotes Cell Cycle Arrest and Apoptosis in MDA-MB-231 Breast Cancer Cells
<b>Background:</b> Natural products play a crucial role in cancer treatment due to their ability to selectively target cancer cells. Andrographolide, a major constituent of <i>Andrographis paniculata</i>, exhibits potential anticancer properties. Considering the pharmacologic...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
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| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/18/7/1026 |
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| Summary: | <b>Background:</b> Natural products play a crucial role in cancer treatment due to their ability to selectively target cancer cells. Andrographolide, a major constituent of <i>Andrographis paniculata</i>, exhibits potential anticancer properties. Considering the pharmacological importance of nitrogen-based heteroaromatic scaffolds, particularly pyrazole motifs, this study aimed to integrate the pyrazole pharmacophore with the andrographolide scaffold to develop novel therapeutic candidates. <b>Methods:</b> Twenty novel 3,19-(N-phenyl-3-aryl-pyrazole) acetals of andrographolide and isoandrographolide were synthesized and characterized using UV-Vis, FT-IR, NMR, and HRMS. Initial anticancer screening was conducted by the National Cancer Institute (NCI), USA, against 60 human cancer cell lines. The most promising compound, <b>1f</b> (R = 4-F), was selected for further biological evaluation in the MDA-MB-231 breast cancer cell line. <b>Results:</b> The MTT assay results demonstrated that compound <b>1f</b> exhibited strong, dose-dependent anti-proliferative effects. The apoptosis analysis of <b>1f</b> revealed a time-dependent increase in apoptotic cells, and cell cycle studies indicated S phase arrest in MDA-MB-231 cells. Antioxidant activity via the DPPH assay identified compounds <b>1b</b> (R = 3-NO<sub>2</sub>) and <b>2b</b> (R = 3-NO<sub>2</sub>) as the most effective radical scavengers. The most active compounds were also evaluated for drug-likeness using in silico Lipinski’s rule assessments. <b>Conclusions:</b> The synthesized 3,19-(N-phenyl-3-aryl-pyrazole) acetals of andrographolide and isoandrographolide exhibited promising anticancer and antioxidant properties. Among them, compound <b>1f</b> showed the most significant activity, supporting its potential as a lead candidate for further anticancer drug development. |
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| ISSN: | 1424-8247 |