Pyrazine-Linked 1,2,3-Triazole Derivatives: Synthesis, Characterization, In Vitro Antimicrobial Evaluation, and Docking Study
摘要
1,2,3-Triazoles are well-known five-membered heterocycles and are more significant in synthetic chemistry and medicinal chemistry due to their large spectrum of biological activities. Pyrazine derivatives are an important class of pharmacophores and possess diverse biological activities. The pyrazine ring is the basic skeleton in several pharmaceutical compounds specifies that pyrazine derivatives are important lead molecules in drug design/development. Keeping in mind the biological importance of triazoles and pyrazine derivatives, in the present work we synthesized a new series of pyrazine–1,2,3-pyrazole hybrids—tert-butyl N-[(1-aryl-1H-[1,2,3]triazol-4-yl)methyl]-N-(pyrazin-2-yl)carbamates—and characterized the products by IR and NMR (1H and 13C) spectroscopy and ESI mass spectrometry. The synthesized compounds were tested for antimicrobial activity against three gram-positive (Bacillus subtilis, Bacillus sphaericus and Staphylococcus aureus) and three gram-negative (Pseudomonas aeruginosa, Klebsiella aerogenes, and Chromobacterim violaceum), as well as for antifungal activity against four fungi: Candida albicans, Aspergillus fumigatus, Trichophyton rubrum, and Trichophyton mentagrophyte. Derivatives with 2-chloro-, 4-chloro-, 4-cyano-, 2-methyl-, and 3-acetylphenyl substituents at the 1-position of the triazole ring demonstrated potent antimicrobial and antifungal activities, comparable to the standard drugs streptomycin and amphotericin B, respectively. Molecular docking studies against the VEGFR2 kinase domain (PDB ID: 4ASD) predicted high binding affinities for most of the novel pyrazine-linked 1,2,3-triazoles, relative to the standard anticancer drug doxorubicin. Taken together, our experimental and in silico results indicate that the novel pyrazine–1,2,3-triazole hybrids represent promising scaffolds for both antimicrobial and anticancer drug design.