Synthesis and Biological Activity of Peptide Derivatives of Iodoquinazolinones/Nitroimidazoles

摘要

Two substituted quinazolinyl/imidazolyl-salicylic acids >5, >6 were synthesized by the reaction of 6-iodo-2-methylbenzoxazin-4-one/5-nitroimidazole with 5-aminosalicylic acid (5-ASA). Coupling of compounds >5 and >6 with different amino acid ester hydrochlorides, dipeptide and tripeptide methyl esters yielded novel quinazolino/imidazolopeptide derivatives >5a-f and >6a-g. The chemical structures of all newly synthesized compounds were confirmed by means of FT-IR, ¹H- and ¹³C-NMR, MS and elemental analysis. Selected peptide ester derivatives were further hydrolyzed by using lithium hydroxide (LiOH) to afford the corresponding acid derivatives >5ba-da and >6ea-ga. All peptide derivatives were assayed for antimicrobial and anthelmintic activities against eight pathogenic microbes and three earthworm species. Among the tested compounds, >5e, >5d, >6e and their hydrolyzed analogs >5da and >6ea exhibited higher antimicrobial activity against Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida albicans, and >5a, >6g and >6ga displayed better antifungal activity against the dermatophytes Trichophyton mentagrophytes and Microsporum audouinii. Moreover, >6f and its hydrolyzed derivative >6fa showed good anthelmintic activity against Megascoplex konkanensis, Pontoscotex corethruses and Eudrilus eugeniea at dose of 2 mg mL^–1.