Potential antimicrobial agents from triazole-functionalized 2H-benzo[b][1, 4]oxazin-3(4H)-ones. Issue 23 (1st December 2017)

• Record Type: Journal Article
• Authors: Bollu, Rajitha; Banu, Saleha; Bantu, Rajashaker; Reddy, A. Gopi; Nagarapu, Lingaiah; Sirisha, K.; Kumar, C. Ganesh; Gunda, Shravan Kumar; Shaik, Kamal
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 23(2017)
• Page Start: 5158
• Page End: 5162
• Publication Date: 2017-12-01
• Subjects: 1, 4-Benzoxazine -- 1, 2, 3 Triazoles -- Antimicrobial activity -- Molecular docking -- Dehydrosqualene synthase; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.10.061
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: A series of substituted triazole-functionalized 2 H -benzo[ b ][1, 4]oxazin-3(4 H )-ones were synthesized and compounds were screened for their in vitro antimicrobial activity against Gram positive and Gram negative strains using Miconazole and Ciprofloxacin as standard drugs. Highlights: A series of novel triazole-functionalized 2 H -benzo[ b ][1, 4]oxazin-3(4 H )-ones (8a –h and9a –h )were efficiently synthesized. Evaluated for their in vitro antimicrobial activity;9c, 9d and9e showed promising activity. Compounds8a, 8c, 8d, 8h, 9c and9f showed good docking with Lys273. Compound9f exhibited highest binding energy of −7.04 kcal/mol. Abstract: A series of substituted triazole functionalized 2 H -benzo[ b ][1, 4]oxazin-3(4 H )-ones were synthesized by employing click chemistry and further characterized based on 1 H NMR, 13 C NMR, IR and mass spectral studies. All the synthesized derivatives were screened for their in vitro antimicrobial activities. Further, molecular docking studies were accomplished to explore the binding interactions between 1, 2, 3-triazol-4-yl-2 H -benzo[ b ][1, 4]oxazin-3(4 H )-one and the active site of Staphylococcus aureus (CrtM) dehydrosqualene synthase (PDB ID:2ZCS ). These docking studies revealed that the synthesized derivatives showed high binding energies and strong H-bond interactions with the dehydrosqualene synthase validating the observed antimicrobial activity data. Based on antimicrobial activity and docking studies, the compounds9c, 9d and9e were identified as promising antimicrobial leads.