Khobragade C N, Bodade Ragini G, Shinde M S, Jaju Deepa R, Bhosle R B, Dawane B S
School of Life Sciences, Biochemistry Research Laboratory, Swami Ramanand Teerth Marathawada University, Nanded, India.
J Enzyme Inhib Med Chem. 2008 Jun;23(3):341-6. doi: 10.1080/14756360701608585.
Xanthine dehydrogenase (XDH) is responsible for the pathological condition called Gout. In the present study different flavones synthesized from chalcone were evaluated in vitro for their inhibitory activity. Inhibitory activity of flavones on XDH was determined in terms of inhibition of uric acid synthesis from Xanthine. The enzymatic activity was found maximum at pH 7.5 and temperature 40 degrees C. The flavones 6-chloro-2-[3-(4-hydroxy-phenyl)-1-phenyl-1-H-pyrazol-4-yl]-chromen-4-one (F(1)) and 6-chloro-7methyl-2-[3-(4-chloro-phenyl)-1-phenyl-1-H-pyrazol-4-yl]-chromen-4-one(F(2)),were noncompetitive and competitive inhibitor with Ki values 1.1 and 0.22 respectively. The flavones (F(1)), (F(2)), 6-chloro-2-[3-(4-chloro-phenyl)-1phenyl-1-H-pyrazol-4-yl]-chromen-4-one(F(3)), 8-bromo-6-chloro-2-[3-(4-chloro-phenyl)-1-phenyl-1-H-pyrazol-4-yl]-chromen-4-one (F(4)), 2-[3-(4-hydroxy-phenyl)-1-phenyl-1-H-pyrazol-4-yl]-chromen-4-one (F(5)) and 6-methyl-2-[3-(4-hydroxy-phenyl)-1-phenyl-1-H-pyrazol-4-yl]-chromen-4-one (F(6)) were also screened for their antimicrobial activity, measured in terms of zone of inhibition. A broad spectrum antifungal activity was obtained against Trichoderma viridae, Candida albicans, Microsporum cannis, Penicillium chrysogenum and Fusarium moniliformae. In case of Aspergillus niger and Aspergillus flavous only spore formation was affected, while antibacterial activity was observed against Staphylococcus aureus, Bacillus subtilis and Serratia marsecens only. The flavones were further analyzed for quantitative structural activity relationship study (QSAR) by using PASS, online software to determine their Pa value. Toxicity and drug relevant properties were revealed by PALLAS software in terms of their molecular weight. Log P values were also studied. The result showed both the F(1) and F(2) flavones as antigout and therefore supports the development of novel drugs for the treatment of gout.
黄嘌呤脱氢酶（XDH）是导致痛风这种病理状况的原因。在本研究中，对从查尔酮合成的不同黄酮类化合物进行了体外抑制活性评估。黄酮类化合物对XDH的抑制活性通过抑制黄嘌呤合成尿酸来测定。酶活性在pH 7.5和温度40摄氏度时最高。黄酮类化合物6-氯-2-[3-(4-羟基苯基)-1-苯基-1-H-吡唑-4-基]-色原酮-4-酮（F(1)）和6-氯-7-甲基-2-[3-(4-氯苯基)-1-苯基-1-H-吡唑-4-基]-色原酮-4-酮（F(2)）分别为非竞争性和竞争性抑制剂，其抑制常数（Ki）值分别为1.1和0.22。还对黄酮类化合物（F(1)）、（F(2)）、6-氯-2-[3-(4-氯苯基)-1-苯基-1-H-吡唑-4-基]-色原酮-4-酮（F(3)）、8-溴-6-氯-2-[3-(4-氯苯基)-1-苯基-1-H-吡唑-4-基]-色原酮-4-酮（F(4)）、2-[3-(4-羟基苯基)-1-苯基-1-H-吡唑-4-基]-色原酮-4-酮（F(5)）和6-甲基-2-[3-(4-羟基苯基)-1-苯基-1-H-吡唑-4-基]-色原酮-4-酮（F(6)）的抗菌活性进行了筛选，通过抑菌圈进行测定。对绿色木霉、白色念珠菌、犬小孢子菌、产黄青霉和串珠镰刀菌具有广谱抗真菌活性。对于黑曲霉和黄曲霉，仅孢子形成受到影响，而仅观察到对金黄色葡萄球菌、枯草芽孢杆菌和粘质沙雷氏菌的抗菌活性。通过使用在线软件PASS对黄酮类化合物进行进一步的定量构效关系研究（QSAR）以确定其预测活性值（Pa值）。通过PALLAS软件根据其分子量揭示了毒性和与药物相关的性质。还研究了脂水分配系数（Log P）值。结果表明F(1)和F(2)这两种黄酮类化合物具有抗痛风作用，因此支持开发用于治疗痛风的新型药物。
