Related Experiment Video
Updated: Nov 1, 2025
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Pyrazole Substituted 9-Anilinoacridines as HER2 Inhibitors Targeting Breast Cancer - An in-silico approach
Kalirajan Rajagopal1, Vulsi Bodhya Sri1, Gowramma Byran1
1Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research-( Deemed to be University), Ooty 643001, The Nilgiris , Tamil Nadu, India.
Background:
Breast cancer is one of the malignant tumours which mainly affect the female population. 20% of the cases of breast cancer are due to the over-expression of Human epidermal growth factor receptor-2 (HER2), which is the dominant tyrosine kinase receptor. In general, 9-anilinoacridine derivatives play an important role in antitumor activity due to their DNA-intercalating properties.
Objective:
Some novel 9-anilinoacridines substituted with pyrazole moiety (1a-z) were designed and their HER2enzyme (PDB id-3PP0) inhibition activity was performed by molecular docking studies using the Glide module of Schrodinger suite 2019-4.
Methods:
Glide module of the Schrodinger suite was used to perform docking studies; qikprop module was used for in-silico ADMET screening and the Prime-MMGBSA module was used for free binding energy calculations. Based on GLIDE scoring functions, we can determine the binding affinity of ligands (1a-z) towards HER2.
Results:
The inhibitory activity of ligands against HER2 was mainly due to the strong hydrophobic and hydrogen bonding interactions. Almost all the compounds 1a-z exhibited a good binding affinity with Glide scores in the range of -4.9 to -9.75, when compared with the standard drugs CK0403 (-4.105) and Tamoxifen (-3.78). From the results of in-silico ADMET properties, it was evident that most of the compounds fell within the recommended values. MM-GBSA binding calculations of the most potent inhibitors were found to be more favourable.
Conclusion:
The results of in-silico studies provide strong evidence for the potential of valuable ligands in pyrazole substituted 9-anilinoacridines as HER2 inhibitors, and the compounds, 1v,s,r,d,a,o with significant Glide scores may produce significant anti-breast cancer activity.
Insights
Novel pyrazole-substituted 9-anilinoacridines show potential as HER2 inhibitors for breast cancer treatment. Molecular docking and in-silico studies indicate strong binding affinity and favorable properties for these compounds.
Area of Science:
- Medicinal Chemistry
- Computational Drug Discovery
- Oncology
Background:
- Breast cancer affects a significant portion of the female population.
- Human epidermal growth factor receptor-2 (HER2) overexpression occurs in 20% of breast cancer cases.
- 9-anilinoacridine derivatives possess antitumor properties via DNA intercalation.
Purpose of the Study:
- To design novel pyrazole-substituted 9-anilinoacridines (compounds 1a-z).
- To evaluate the HER2 enzyme inhibition activity of these novel compounds.
- To perform molecular docking studies to assess binding affinity.
Main Methods:
- Molecular docking studies using the Glide module of Schrodinger suite.
- In-silico ADMET screening utilizing the qikprop module.
- Free binding energy calculations with the Prime-MMGBSA module.
Main Results:
- Compounds exhibited good binding affinity to HER2, with Glide scores ranging from -4.9 to -9.75.
- Hydrophobic and hydrogen bonding interactions were key to inhibitory activity.
- In-silico ADMET properties for most compounds were within recommended ranges, and MM-GBSA calculations supported favorable binding.
Conclusions:
- Pyrazole-substituted 9-anilinoacridines show promise as HER2 inhibitors.
- Compounds 1v, 1s, 1r, 1d, 1a, and 1o demonstrated significant Glide scores, suggesting potential anti-breast cancer activity.
