Chinese Journal of Organic Chemistry >
Synthesis and Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity Evaluation of Novel N-Acylhydrazone Derivatives Containing Carbazole and Aromatic Ring/Aromatic Fused Heterocycle
Received date: 2021-05-17
Revised date: 2021-06-21
Online published: 2021-07-13
Supported by
Natural Science Foundation of Liaoning Province(20102126)
In order to find more efficient and low toxicity protein tyrosine phosphatase 1B (PTP1B) inhibitors, a series of novel N-acylhydrazone derivatives containing carbazole and aromatic ring/aromatic fused heterocycle 6~8 and 11 were designed and synthesized. Their structures and configurations were confirmed by IR, 1H NMR, 13C NMR, two-dimensional NMR spectra (including 1H-1H COSY and NOESY) and elemental analysis. The inhibitory activities of all the target compounds against PTP1B were evaluated. The experimental results indicated that all the target compounds had potent inhibitory activity against PTP1B, and the activities were higher than the control drug oleanolic acid except for N'-[9-(2-chlorothiazole-5-methyl)carbazole-3-methylene]-2-phenylaminoacethydrazide (6a), N'-[9-(2-chlorothiazole-5-methyl)carbazole-3-methylene]- 2-(4-methylphenylamino)acethydrazide (6b), N'-[9-(2-chlorothiazole-5-methyl)carbazole-3-methylene]-2-(3-nitrophenylamino)acethydrazide (6g) and N'-[9-(2-chlorothiazole-5-methyl)carbazole-3-methylene)-2-(4-nitrophenylamino) acethydrazide (6h). Among them, N,N'-[(9-butylcarbazolyl)-3,6-dimethylene]-2,2'-[di(4-nitrophenylamino)]bisacetohydrazide (11b) had the highest inhibitory activity against PTP1B with IC50 of (0.89±0.06) μmol/L. Molecular docking was used to study the bind of the representative target compounds N'-[9-(2-chlorothiazole-5-methyl)carbazole-3-methylene]-2-(4-bromophenylamino)acethydrazide (6d), N'-[9-(2-chlorothiazole-5-methyl)carbazole-3-methylene)-2-((2-(1-naphthyloxy)methyl)benzimidazol-1-yl)- acethydrazide (7f) and 11b with PTP1B enzyme, respectively.
Key words： PTP1B inhibitor; carbazole; N-actylhydrazone; synthesis; molecular docking
Yingjun Li , Ledi Lin , Jihong Liu , Lixin Gao , Li Sheng , Kun Jin , Xuejie Liu , Hongjing Yang , Jia Li . Synthesis and Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity Evaluation of Novel N-Acylhydrazone Derivatives Containing Carbazole and Aromatic Ring/Aromatic Fused Heterocycle[J]. Chinese Journal of Organic Chemistry, 2021 , 41(9) : 3593 -3607 . DOI: 10.6023/cjoc202105032
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