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Functionalized spirooxindole-indolizine hybrids: Stereoselective green synthesis and evaluation of anti-inflammatory effect involving TNF-α and nitrite inhibition
European Journal of Medicinal Chemistry ( IF 6.7 ) Pub Date : 2018-05-03
Raju Suresh Kumar, Paulrayer Antonisamy, Abdulrahman I. Almansour, Natarajan Arumugam, Govindasami Periyasami, Mohammad Altaf, Ha-Rim Kim, Kang-Beom Kwon

Stereoselective synthesis of a small library of novel spiroheterocyclic hybrids including indolizine, oxindole, and substituted piperidine units has been accomplished in [bmim]Br using a [3 + 2] cycloaddition strategy in good yield and were tested for their anti-inflammatory activities. The effects compounds (4a-o) against inflammation were studied using carrageenan-induced hind paw oedema, croton oil-induced ear oedema, and cotton pellet-induced granuloma models. Among the heterocyclic hybrids, compounds 4d, 4g, and 4o showed significant anti-inflammatory activities against acute and chronic inflammatory models. These compounds also showed significant inhibition of PGE2, TNF-α, and nitrite levels in carrageenan-induced hind paw oedema. Thus it is evident from our study that these novel spiroheterocyclic hybrids 4d, 4g, and 4o displayed significant anti-inflammatory effects that involve the reduction of PGE2, TNF-α, and nitrite levels.



中文翻译:

功能化螺虫吲哚-吲哚嗪混合物:立体选择性绿色合成和涉及TNF-α和亚硝酸盐抑制作用的抗炎作用评估

使用[3 + 2]环加成策略,在[bmim] Br中完成了一个新颖的螺杂环混合物(包括吲哚利嗪,羟吲哚和取代的哌啶单元)的小型文库的立体选择性合成,并获得了良好的收率,并对其抗炎活性进行了测试。使用角叉菜胶诱导的后爪水肿,巴豆油诱导的耳部水肿和棉丸诱导的肉芽肿模型研究了化合物(4a-o)对炎症的影响。在杂环杂种中,化合物4d4g4o对急性和慢性炎症模型表现出显着的抗炎活性。这些化合物还显示出对PGE 2的显着抑制作用角叉菜胶诱发的后爪水肿中的TNF,α和亚硝酸盐水平。因此,从我们的研究中可以明显看出,这些新型螺杂环杂种4d4g4o表现出显着的抗炎作用,涉及降低PGE 2,TNF-α和亚硝酸盐水平。

更新日期:2018-05-03
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