Alafeefy Ahmed M, Bakht Mohammed A, Ganaie Majid A, Ansarie Mohd N, El-Sayed Nahed N, Awaad Amani S
Department of Pharmaceutical Chemistry, College of Pharmacy, Salman Bin Abdulaziz University, PO Box 173, Alkharj 11942, Saudi Arabia.
Department of Pharmaceutical Chemistry, College of Pharmacy, Salman Bin Abdulaziz University, PO Box 173, Alkharj 11942, Saudi Arabia.
Bioorg Med Chem Lett. 2015 Jan 15;25(2):179-83. doi: 10.1016/j.bmcl.2014.11.088. Epub 2014 Dec 6.
A series of certain novel Schiff bases as fenamate isosteres (VI:a-k) were synthesized to locate analgesic, anti-inflammatory agent with minimal ulcerogenic potential. The structures of the newly synthesized compounds were elucidated on the basis of their elemental analysis as well as IR, and NMR and mass spectroscopic data. All the compounds were evaluated for their anti-inflammatory activity by carrageenan induced paw oedema method. The compounds possessing good anti-inflammatory activity were further tested for analgesic, ulcerogenic, lipid peroxidation potentials and liver toxicity. Compounds (VI-c), (VI-f), (VI-h) and (VI-i) showed the best anti-inflammatory and significant analgesic activities at doses comparable to that of the standard drug Indomethacin. However, compounds (VI-c) and (VI-f) could be considered the most potent anti-inflammatory and analgesic molecules with maximum reduction in gastro-intestinal ulceration with no hepatocyte necrosis or liver degeneration.
合成了一系列作为芬那酸盐类似物的新型席夫碱（VI:a-k），以寻找具有最小致溃疡潜力的镇痛、抗炎剂。根据元素分析以及红外、核磁共振和质谱数据阐明了新合成化合物的结构。通过角叉菜胶诱导的爪肿胀法评估所有化合物的抗炎活性。对具有良好抗炎活性的化合物进一步测试其镇痛、致溃疡、脂质过氧化潜力和肝毒性。化合物（VI-c）、（VI-f）、（VI-h）和（VI-i）在与标准药物吲哚美辛相当的剂量下表现出最佳的抗炎和显著的镇痛活性。然而，化合物（VI-c）和（VI-f）可被认为是最有效的抗炎和镇痛分子，能最大程度减少胃肠道溃疡，且无肝细胞坏死或肝变性。
