当前位置：
X-MOL 学术
›
RSC Med. Chem.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Design, synthesis and preliminary antimicrobial evaluation of N-alkyl chain-tethered C-5 functionalized bis-isatins
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2017-09-19 00:00:00 , DOI: 10.1039/c7md00434f Amandeep Singh 1, 2, 3, 4 , Nisha Nisha 1, 2, 3, 4 , Trpta Bains 5, 6, 7, 8, 9 , Hye Jee Hahn 5, 6, 7, 8, 9 , Nicole Liu 9, 10, 11, 12 , Christina Tam 9, 13, 14, 15, 16 , Luisa W. Cheng 9, 13, 14, 15, 16 , Jong Kim 9, 13, 14, 15, 16 , Anjan Debnath 5, 6, 7, 8, 9 , Kirkwood M. Land 9, 10, 11, 12 , Vipan Kumar 1, 2, 3, 4
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2017-09-19 00:00:00 , DOI: 10.1039/c7md00434f Amandeep Singh 1, 2, 3, 4 , Nisha Nisha 1, 2, 3, 4 , Trpta Bains 5, 6, 7, 8, 9 , Hye Jee Hahn 5, 6, 7, 8, 9 , Nicole Liu 9, 10, 11, 12 , Christina Tam 9, 13, 14, 15, 16 , Luisa W. Cheng 9, 13, 14, 15, 16 , Jong Kim 9, 13, 14, 15, 16 , Anjan Debnath 5, 6, 7, 8, 9 , Kirkwood M. Land 9, 10, 11, 12 , Vipan Kumar 1, 2, 3, 4
Affiliation
|
A series of N-alkyl-tethered C-5 functionalized bis-isatins were synthesized and evaluated for their antimicrobial activity against pathogenic microorganisms. The preliminary evaluation studies revealed compound 4t, with an optimal combination of a bromo substituent at the C-5 position of the isatin ring and a propyl chain linker, being the most active among the synthesized series exhibiting an IC50 value of 3.72 μM against Trichomonas vaginalis while 4j exhibited an IC50 value of 14.8 μM against Naegleria fowleri, more effective than the standard drug miltefosine. Compound 3f with an octyl spacer length was the most potent among the series against Giardia lamblia with an IC50 of 18.4 μM while 3d exhibited an IC50 of 23 μM against Entamoeba histolytica. This library was also screened against the fungal pathogen Aspergillus parasiticus. A number of the compounds demonstrated potency against this fungus, illustrating a possible broad-spectrum activity. Furthermore, an evaluation of these synthesized compounds against a panel of normal flora bacteria revealed them to be non-cytotoxic, demonstrating the selectivity of these compounds. This observation, in combination with previous studies that found isatin to be non-toxic to humans, presents a new possible scaffold for drug discovery against these important protozoal pathogens of humans and animals.
中文翻译：
N烷基链连接的C-5官能化双伊斯廷汀的设计，合成和初步抗菌评估
合成了一系列的N-烷基束缚的C-5官能化的双-isatins，并评估了它们对病原微生物的抗菌活性。初步评估研究表明，化合物4t具有最佳的组合，该化合物在isatin环的C-5位置具有一个溴取代基和一个丙基链接头，是合成的系列中活性最高的化合物，其抗滴虫的IC 50值为3.72μM而4j的阴道菌对家禽（Naegleria fowleri）的IC 50值为14.8μM，比标准药物miltefosine更有效。化合物3f具有辛基间隔长度的是对抗贾第鞭毛虫的系列中最有力的，IC 50为18.4μM，而3d对溶血变形杆菌的IC 50为23μM。还针对真菌病原体寄生曲霉筛选了该文库。许多化合物显示出对这种真菌的效力，说明了可能的广谱活性。此外，针对一组正常的菌群细菌对这些合成的化合物进行了评估，结果表明它们具有非细胞毒性，证明了这些化合物的选择性。这项发现与先前发现伊斯兰汀对人类无毒的研究相结合，为针对人类和动物这些重要原生动物病原体的药物发现提供了一种新的可能支架。
更新日期：2017-10-18
中文翻译：
N烷基链连接的C-5官能化双伊斯廷汀的设计，合成和初步抗菌评估
合成了一系列的N-烷基束缚的C-5官能化的双-isatins，并评估了它们对病原微生物的抗菌活性。初步评估研究表明，化合物4t具有最佳的组合，该化合物在isatin环的C-5位置具有一个溴取代基和一个丙基链接头，是合成的系列中活性最高的化合物，其抗滴虫的IC 50值为3.72μM而4j的阴道菌对家禽（Naegleria fowleri）的IC 50值为14.8μM，比标准药物miltefosine更有效。化合物3f具有辛基间隔长度的是对抗贾第鞭毛虫的系列中最有力的，IC 50为18.4μM，而3d对溶血变形杆菌的IC 50为23μM。还针对真菌病原体寄生曲霉筛选了该文库。许多化合物显示出对这种真菌的效力，说明了可能的广谱活性。此外，针对一组正常的菌群细菌对这些合成的化合物进行了评估，结果表明它们具有非细胞毒性，证明了这些化合物的选择性。这项发现与先前发现伊斯兰汀对人类无毒的研究相结合，为针对人类和动物这些重要原生动物病原体的药物发现提供了一种新的可能支架。
京公网安备 11010802027423号