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Novel 4-thiophenyl-pyrazole, pyridine, and pyrimidine derivatives as potential antitumor candidates targeting both EGFR and VEGFR-2; design, synthesis, biological evaluations, and<i>in silico</i>studies

Samia M. Al-Muntaser, Ahmed A. Al‐Karmalawy, Abeer M. El‐Naggar, Ali Kh. Khalil, Nour E. A. Abd El‐Sattar, Eslam M. Abbass

2023RSC Advances51 citationsDOIOpen Access PDF

Abstract

strains. The findings of the antimicrobial tests revealed that most of the investigated compounds exhibited strong to moderate antibacterial and antifungal effects. Furthermore, to understand the pattern by which the investigated compounds bound to the active site, all the newly synthesized candidates were subjected to two different docking processes into the EGFR and VEGFR-2 binding sites. Besides, we tried to correlate compound 10b and the reference drugs (erlotinib and sorafenib) through DFT calculations. Finally, following the biological data of the new pyrazole, pyridine, and pyrimidine derivatives as anticancer and antimicrobial candidates, we concluded a very interesting SAR for further optimization.

Topics & Concepts

PyrazolePyrimidineIn silicoPyridineChemistryCombinatorial chemistryStereochemistryBiochemistryMedicinal chemistryGeneSynthesis and biological activityBioactive Compounds and Antitumor AgentsMulticomponent Synthesis of Heterocycles