Synthesis and Biological Activity of Peptide Derivatives of Iodoquinazolinones/Nitroimidazoles

Abstract: Two substituted quinazolinyl/imidazolyl-salicylic acids 5, 6 were synthesized bythe reaction of 6-iodo-2-methylbenzoxazin-4-one/5-nitroimidazole with 5-aminosalicylicacid (5-ASA). Coupling of compounds 5 and 6 with different amino acid esterhydrochlorides, dipeptide and tripeptide methyl esters yielded novelquinazolino/imidazolopeptide derivatives 5a-f and 6a-g. The chemical structures of allnewly synthesized compounds were confirmed by means of FT-IR, ¹H- and ¹³C-NMR, MSand elemental analysis. Selected peptide ester derivatives were further hydrolyzed by usinglithium hydroxide (LiOH) to afford the corresponding acid derivatives 5ba-da and 6e_a-g_a.All peptide derivatives were assayed for antimicrobial and anthelmintic activities againsteight pathogenic microbes and three earthworm species. Among the tested compounds, 5e,5d, 6e and their hydrolyzed analogs 5d_a and 6e_a exhibited higher antimicrobial activityagainst Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida albicans, and 5_a,6g and 6g_a displayed better antifungal activity against the dermatophytes Trichophytonmentagrophytes and Microsporum audouinii. Moreover, 6f and its hydrolyzed derivative6f_a showed good anthelmintic activity against Megascoplex konkanensis, Pontoscotexcorethruses and Eudrilus eugeniea at dose of 2 mg mL^–1.