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Synthesis of Fused Isoxazoles of Iodoquinol as in vitro EGFR Aiming Anticancer Agents

Karthik Bokkala, Ashok Kumar Bapuram, Narasimha Swamy Thirukovela, Satheesh Kumar Nukala

2024ChemistrySelect10 citationsDOIOpen Access PDF

Abstract

Abstract We have presented the synthesis of some new quinoline linked fused isoxazoles via copper (I) catalyzed azide alkyne cycloaddition (CuAAC) followed by intramolecular C−H arylation of isoxazole ring using PdCl 2 (PPh 3 ) 2 catalyst. All the synthesized compounds were investigated for anticancer activity against three human breast cancer cell lines such as MCF‐7, MDA‐MB‐468 and MDA‐MB‐231 using MTT assay and 5‐fluorouracil (5‐FU) was used as a standard drug. In this study, three compounds were exhibited greater activity than reference drug 5‐FU against three cell lines which further screened for in vitro tyrosine kinase EGFR inhibition and molecular docking studies by taking EGFR protein as the target. Finally, insilico pharmacokinetic profile of the same compounds was obtained using SWISSADME where two compounds following Lipinski, Ghose, Veber, Egan, and Muegge rules.

Topics & Concepts

ChemistryLipinski's rule of fiveClick chemistryIn vitroDocking (animal)MTT assayIsoxazoleCombinatorial chemistryTyrosine kinaseStereochemistryCycloadditionIn silicoPharmacologyBiochemistryCatalysisReceptorBiologyMedicineGeneNursingClick Chemistry and ApplicationsComputational Drug Discovery MethodsProtein Degradation and Inhibitors