新型双吡唑啉酮作为活性氧抑制的潜在先导化合物；环境友好的绿色合成、结构表征及体外研究
New Bis-Pyrazolones as Potential Leads for ROS Inhibition; Environment Friendly Green Synthesis, Structural Characterization, and In Vitro Studies.
作者信息
Yousuf Sahar, Khan Khalid M, Salar Uzma, Jabeen Almas, Ahmed Shakil, Muhammad Munira T, Faheem Aisha, Perveen Shahnaz
机构信息
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.
Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia.
出版信息
Med Chem. 2018;14(5):536-548. doi: 10.2174/1573406414666180112122001.
BACKGROUND
Pyrazolones have identified as significant antioxidant agents and many marketed and clinically prescribed NSAIDs have pyrazolone ring as main scaffold.
METHOD
Keeping in consideration the antioxidant potential of pyrazolone scaffold, new bispyrazolones 3-30 were synthesized by a green and enviroment friendly reaction route, in which two equivalents of 1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-ol were treated with one equivalent of benzaldehyde derivatives without any catalyst. All compounds were structurally characterzied by 1H-NMR and FAB analysis. 13C-NMR of selected compounds was also recorded. All compounds gave satisfactory elemental analyses and found in good agreement with calculated values.
RESULTS
Synthetic bis-pyrazolones 3-30 were evaluated for their oxidative burst inhibitory effect of zymosan stimulated whole blood phagocytes by using luminol enhanced chemilluminescence technique. All molecules demonstrated the potent ROS inhibition activity in the range of IC50 = 1.2 ± 0.1-48.8 ± 3.9 µM as compared to the standard ibuprofen (IC50 = 54.2 ± 9.2 μM). The purity of active compounds was checked by HPLC.
CONCLUSION
This study has identified a number of non-acidic lead molecules for future research on ROS inhibitors.
背景
吡唑啉酮已被确认为重要的抗氧化剂，许多上市的和临床处方的非甾体抗炎药都以吡唑啉酮环作为主要骨架。
方法
考虑到吡唑啉酮骨架的抗氧化潜力，通过绿色环保的反应路线合成了新型双吡唑啉酮3 - 30，即两当量的1 - (4 - 氯苯基)-3 - 甲基-1H - 吡唑 - 5 - 醇与一当量的苯甲醛衍生物在无任何催化剂的情况下反应。所有化合物通过1H - NMR和FAB分析进行结构表征。还记录了所选化合物的13C - NMR。所有化合物的元素分析结果令人满意，与计算值吻合良好。
结果
采用鲁米诺增强化学发光技术，对合成的双吡唑啉酮3 - 30进行了对酵母聚糖刺激的全血吞噬细胞氧化爆发抑制作用的评估。与标准布洛芬（IC50 = 54.2 ± 9.2 μM）相比，所有分子均表现出强大的ROS抑制活性，IC50范围为1.2 ± 0.1 - 48.8 ± 3.9 μM。通过HPLC检查活性化合物的纯度。
结论
本研究确定了一些非酸性先导分子，用于未来对ROS抑制剂的研究。
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