Chinese Journal of Organic Chemistry >
Synthesis, Antibacterial and Antifungal Evaluation of Rhodanine Derivatives Bearing Quinoxalinyl Imidazole Moiety as ALK5 Inhibitors
Received date: 2021-06-07
Revised date: 2021-07-12
Online published: 2021-08-10
Supported by
National Natural Science Foundation of China(8206023)
Transforming growth factor-β (TGF-β) is overexpressed in many diseases, and is an important target for treating tumors. Two series of 3-substituted-5-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methylene)-2-thioxo- thiazolidin-4-ones (12, 13a~13e, and 14a~14h) were synthesized and evaluated for their activin receptor-like kinase 5 (ALK5) inhibition activity. Among these compounds, (Z)-6-(5-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol- 2-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl)hexanoic acid (13e) showed the highest activity (IC50=0.451 µmol•L–1) against ALK5 kinase, which had a good selectivity index of >22 against p38α MAP kinase, with 5.0-fold more selectivity than the clinical candidate of LY-2157299. These rhodanine compounds showed good antifungal activity and high selectivity against both Gram-positive and Gram-negative bacteria. These compounds showed similar or higher antifungal activity (MIC=0.5 or 1 µg/mL) to the positive control compound fluconazole (MIC=1 µg/mL).
Key words: rhodanine; TGF-β; quinoxalinyl imidazole; ALK5 inhibitor; antimicrobial; antifungal
Lizhuo Han , Limin Zhao , Huimin Wang , Tong Dou , Fangyan Guo , Junda Qi , Wenbo Xu , Lianxun Piao , Xuejun Jin , Fen'er Chen , Huri Piao , Changji Zheng , Chenghua Jin . Synthesis, Antibacterial and Antifungal Evaluation of Rhodanine Derivatives Bearing Quinoxalinyl Imidazole Moiety as ALK5 Inhibitors[J]. Chinese Journal of Organic Chemistry, 2021 , 41(11) : 4428 -4436 . DOI: 10.6023/cjoc202106015
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