Reddy M V Ramana, Billa Vinay K, Pallela Venkat R, Mallireddigari Muralidhar R, Boominathan Rengasamy, Gabriel Jerome L, Reddy E Premkumar
Fels Institute for Cancer Research, Temple University School of Medicine, 3307 North Broad Street, Philadelphia, PA 19140-5101, USA.
Bioorg Med Chem. 2008 Apr 1;16(7):3907-16. doi: 10.1016/j.bmc.2008.01.047. Epub 2008 Jan 30.
A series of 20 novel 1-(4-sulfamylphenyl)-3-trifluoromethyl-5-indolyl pyrazolines were designed, synthesized, and screened in vitro for anti-inflammatory activity. These compounds were designed for evaluation as dual inhibitors of cyclooxygenases (COX-1 and COX-2) and lipoxygenases (LOX-5, LOX-12, and LOX-15) that are responsible for inflammation and pain. All pyrazoline molecules prepared are optically active and compounds that are more potent in COX-2 inhibitory activity (5a and 5f) were resolved by chiral column and each enantiomer was tested for cyclooxygenase inhibitory activity. Molecular modeling and comparison of molecular models of 5a enantiomers with that of celecoxib model shows that 5a (enantiomer-1) and 5a (enantiomer-2) have more hydrogen bonding interactions in the catalytic domain of COX-2 enzyme than celecoxib. Compounds 5a, 5e, and 5f showed moderate to good LOX-5 and LOX-15 inhibitory activity and this is comparable to that of celecoxib and more potent than rofecoxib.
设计、合成了一系列20种新型的1-(4-氨磺酰苯基)-3-三氟甲基-5-吲哚基吡唑啉，并对其进行体外抗炎活性筛选。这些化合物被设计用于评估作为环氧化酶（COX-1和COX-2）和脂氧合酶（LOX-5、LOX-12和LOX-15）的双重抑制剂，这些酶与炎症和疼痛有关。所制备的所有吡唑啉分子均具有光学活性，对COX-2抑制活性更强的化合物（5a和5f）通过手性柱拆分，每种对映体均进行环氧化酶抑制活性测试。5a对映体的分子模型与塞来昔布模型的分子模型进行分子建模和比较表明，5a（对映体-1）和5a（对映体-2）在COX-2酶的催化结构域中比塞来昔布具有更多的氢键相互作用。化合物5a、5e和5f表现出中度至良好的LOX-5和LOX-15抑制活性，这与塞来昔布相当，且比罗非昔布更有效。
