Shoaib Mohammad, Shah Syed Wadood Ali, Ali Niaz, Umar Naveed, Shah Ismail, - Shafiullah, Tahir Muhammad Nawaz
Department of Pharmacy, University of Malakand, Chakdara, Dir Lower, KPK, Pakistan.
Department of Pharmacology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, KPK, Pakistan.
Pak J Pharm Sci. 2019 May;32(3):911-917.
Flavonoids are phenolic compounds that have always attracted pharmaceutical researchers and food manufacturers. Nature has indirectly provided us flavones in our daily diet i.e. tea, fruits, juices and vegetables. Flavones have got special position in research field of natural and synthetic organic chemistry due to their biological capabilities. Three substituted flavone derivatives have been synthesized from substituted O-hydroxy acetophenones and 4-trifluoromethyl benzaldehyde in good yield. The structures have been established by different spectroscopic techniques like HNMR CNMR, IR spectroscopy. The compounds were then screened for their enzyme inhibition potential and antinociceptive response in mice models with writhings induced by acetic acid, tail immersion and formalin-induced nociception assay procedures and structure activity relationship was established. The effects following pretreatment with naloxone were also studied to reveal the involvement of opioid receptors in the antinociceptive action. The flavone derivatives showed moderate to weak inhibition against LOX. Moreover, significant to moderate decrease in the number of abdominal constrictions, increase in paw-licking response time in both phases and a significant raise in latency time in nociception models. Moreover, the antinociceptive response was significantly attenuated by pretreatment with opioid receptor antagonist suggesting the involvement of opioidergic system in the analgesic action. The flavone derivatives showed analgesic response in all models of nociception suggesting the possible involvement of opioidergic system in the antinociceptive action.
黄酮类化合物是一类酚类化合物,一直吸引着药物研究人员和食品制造商。大自然在我们的日常饮食中,如茶、水果、果汁和蔬菜中,间接地为我们提供了黄酮。由于黄酮的生物学特性,它们在天然和合成有机化学研究领域中占据着特殊的地位。由取代的邻羟基苯乙酮和4-三氟甲基苯甲醛合成了三种取代黄酮衍生物,产率良好。通过不同的光谱技术,如核磁共振氢谱(HNMR)、核磁共振碳谱(CNMR)、红外光谱(IR)确定了其结构。然后在小鼠模型中,通过乙酸诱导扭体、尾部浸入和福尔马林诱导疼痛测定程序,对这些化合物的酶抑制潜力和抗伤害感受反应进行筛选,并建立了构效关系。还研究了用纳洛酮预处理后的效果,以揭示阿片受体在抗伤害感受作用中的参与情况。黄酮衍生物对脂氧合酶(LOX)表现出中度至弱的抑制作用。此外,在伤害感受模型中,腹部收缩次数显著减少至中度减少,两个阶段的舔爪反应时间增加,潜伏期时间显著延长。此外,阿片受体拮抗剂预处理可显著减弱抗伤害感受反应,表明阿片能系统参与了镇痛作用。黄酮衍生物在所有伤害感受模型中均表现出镇痛反应,表明阿片能系统可能参与了抗伤害感受作用。