Dahiya Rajiv, Kumar Anil, Yadav Rakesh
Department of Pharmaceutical Chemistry, Rajiv Academy for Pharmacy, Mathura-281001 (UP), India.
Molecules. 2008 Apr 24;13(4):958-76. doi: 10.3390/molecules13040958.
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, (1)H- and (13)C-NMR, MSand elemental analysis. Selected peptide ester derivatives were further hydrolyzed by using lithium 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 against eight 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 activity against Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida albicans, and 5(a),6g and 6g(a) displayed better antifungal activity against the dermatophytes Trichophyton mentagrophytes and Microsporum audouinii. Moreover, 6f and its hydrolyzed derivative6f(a) showed good anthelmintic activity against Megascoplex konkanensis, Pontoscotex corethruses and Eudrilus eugeniea at dose of 2 mg mL(-1).
通过6-碘-2-甲基苯并恶嗪-4-酮/5-硝基咪唑与5-氨基水杨酸（5-ASA）反应合成了两种取代喹唑啉基/咪唑基水杨酸5和6。化合物5和6与不同的氨基酸酯盐酸盐、二肽和三肽甲酯偶联，得到了新型喹唑啉/咪唑肽衍生物5a-f和6a-g。通过傅里叶变换红外光谱（FT-IR）、氢核磁共振（¹H-NMR）、碳核磁共振（¹³C-NMR）、质谱（MS）和元素分析确定了所有新合成化合物的化学结构。选用的肽酯衍生物用氢氧化锂（LiOH）进一步水解，得到相应的酸衍生物5ba-da和6e(a)-g(a)。对所有肽衍生物进行了针对8种致病微生物和3种蚯蚓的抗菌和驱虫活性测定。在测试的化合物中，5e、5d、6e及其水解类似物5d(a)和6e(a)对铜绿假单胞菌、肺炎克雷伯菌和白色念珠菌表现出较高的抗菌活性，5(a)、6g和6g(a)对须癣毛癣菌和奥杜盎小孢子菌等皮肤癣菌表现出较好的抗真菌活性。此外，6f及其水解衍生物6f(a)在2 mg mL⁻¹剂量下对康卡纳巨蚓、科氏环毛蚓和赤子爱胜蚓表现出良好的驱虫活性。
