Synthesis and characterization of new isatin hybrids based on isatin-coumarin hybrid as potent antioxidant, anti-inflammatory and antimicrobial agents

Iisatin hybrids have emerged as effective weapons against diseases. In this context, chalcone tethered isatin-coumarin hybrid 3 was synthesized and used as a building block for the preparation of a new series of isatin-pyrazole, isatin-bridged dibenzo-diazonin and isatin-coumarin hybrids 4–10 by reaction with ammonium acetate or primary aromatic amines. The hybrids 4–10 were linked with bioactive linkers named ethene, furan, pyrrole or its derivatives. Through another reaction route, the polyfused pyrano-indoles 11–13 were synthesized by one pot reaction of isatin - coumarin hybrid 3 with some primary amines having electron donating substituents. The chemical structures of the synthesized compounds were evaluated by infrared, nuclear magnetic resonance, MS and elemental analyses. The synthesized compounds were screened for their antioxidant, anti-inflammatory and antimicrobial effects. The results revealed that all the compounds have high antioxidant activity and some of these compounds provide anti-inflammatory effects close to that of indomethacin. While the antimicrobial effects were studied against both Gram - positive and Gram-negative bacteria, greater activity for compounds 3 and 6 was observed against Gram-positive bacteria (B. Subtilis). While compounds 3, 4, 6, 9 and 10 were active against Gram-negative bacteria (E. coli).靛红（Isatin）类杂合物已被证实为对抗疾病的有效制剂。在此研究背景下，课题组以查尔酮连接的靛红-香豆素杂合物3为构筑砌块，通过其与乙酸铵或芳香伯胺的反应，制备得到一系列新型靛红-吡唑、靛红桥联二苯并二氮杂卓以及靛红-香豆素类杂合物4~10。杂合物4~10通过乙烯、呋喃、吡咯及其衍生物这类生物活性连接臂进行连接。 通过另一合成路径，以靛红-香豆素杂合物3与若干带有给电子取代基的芳香伯胺为原料，经一锅法反应合成了多稠合吡喃并吲哚类化合物11~13。 通过红外光谱、核磁共振波谱、质谱以及元素分析对所合成化合物的化学结构进行了表征鉴定。随后对所有合成化合物开展了抗氧化、抗炎以及抗菌活性筛选实验。 实验结果表明，所有受试化合物均表现出优异的抗氧化活性，其中部分化合物的抗炎活性可媲美吲哚美辛（indomethacin）。针对抗菌活性的研究覆盖革兰氏阳性菌与革兰氏阴性菌两类：化合物3与6对革兰氏阳性菌枯草芽孢杆菌（B. Subtilis）表现出更为突出的抑制活性；化合物3、4、6、9与10则对革兰氏阴性菌大肠杆菌（E. coli）具有抑制活性。