Background: Breast cancer is one of the malignant tumours which mainly affect the female population. Total 20% of the cases of breast cancer are due to overexpression of Human epidermal growth factor receptor-2 (HER2), which is the dominant tyrosine kinase receptor. In general, 9-anilinoacridine derivatives play an important role as antitumor agents 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 evaluated 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-MM-GBSA module was used for free binding energy calculations. Using 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 have a good binding affinity with Glide scores in the range of -4.9 to -9.75 compared to the standard drugs CK0403(-4.105) and Tamoxifen (-3.78). From the results of in-silico ADMET properties, most of the compounds fall within the recommended values. MM-GBSA binding calculations of the most potent inhibitors are more favourable. Conclusion: The results of in-silico studies provide strong evidence for the consideration of valuable ligands in pyrazole substituted 9-anilinoacridines as potential HER2 inhibitors, and the compounds, 1v,s,r,d, a,o with significant Glide scores may produce significant anti-breast cancer activity for further development.
Coronavirus Disease 2019 (COVID-19), a life-threatening viral disease affected first in Wuhan, China, and quickly spread to more than 200 countries in the world in the year 2020. So many scientists are trying to discover novel drugs and vaccines for coronavirus and treatment for COVID-19. In the present article, in-silico studies have been performed to explore the binding modes of Thiazine substituted 9-anilinoacridines (1a-z) against SARS CoV 2 main protease (PDB id - 5R82) targeting the coronavirus using Schrodinger suit 2019-4. The molecular docking studies are performed by Glide module, in-silico ADMET screening was performed by Qik prop module, and the binding free energy of ligands was calculated using PRIME MM-GB/SA module of Schrodinger suite 2019-4, Maestro 21.2 version. From the in-silico results, Thiazine substituted 9-anilinoacridines like 1m, 1j, 1s and 1b are significantly active against SARS CoV 2 main protease with Glide score more than -5.4 when compared with the currently recommended drug for COVID19, Hydroxychloroquine (G score -5.47). The docking results of the Thiazine substituted 9-anilinoacridines exhibited similar mode of interactions with COVID19 and the residues GLN19, THR24, THR25, THR26, LEU27, HIE41, SER46, MET49, ASN142, GLN143, HIE164, MET165, ASP187, ARG188 and GLN189, play a crucial role in binding with ligands.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.