新型非细胞毒性脲酶抑制剂——酮砜衍生物的合成
Synthesis of -Ketosulfone Derivatives As New Non-Cytotoxic Urease Inhibitors .
作者信息
Iqbal Sarosh, Khan Ajmal, Nazir Rashid, Kiran Shumaila, Perveen Shahnaz, Khan Khalid M, Choudhary Muhammad I
机构信息
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.
Department of Applied Chemistry, Government College University, Faisalabad-38000, Faisalabad, Pakistan.
出版信息
Med Chem. 2020;16(2):244-255. doi: 10.2174/1573406415666190415163309.
BACKGROUND
Peptic ulcer and urolithiasis are largely due to infection caused by ureaseproducing bacteria. Therefore, the discovery of urease inhibitors is an important area of medicinal chemistry research.
OBJECTIVE
The main aim of the work was to identify novel urease inhibitors with no cytotoxicity.
METHODS
During the current study, a series of β-ketosulfones 1-26 was synthesized in two steps and evaluated for their in vitro urease inhibition potential.
RESULTS
Out of twenty-six compounds, seventeen have shown good to significant urease inhibitory activity with IC50 values ranging between 49.93-351.46 µM, in comparison to standard thiourea (IC50 = 21 ± 0.11 µM). Moreover, all compounds found to be non-cytotoxic against normal 3T3 cell line.
CONCLUSION
This study has identified β-ketosulfones as novel and non-cytotoxic urease inhibitors.
背景
消化性溃疡和尿路结石很大程度上是由产脲酶细菌感染引起的。因此，脲酶抑制剂的发现是药物化学研究的一个重要领域。
目的
这项工作的主要目的是鉴定无细胞毒性的新型脲酶抑制剂。
方法
在本研究中，通过两步合成了一系列β-酮砜1-26，并评估了它们的体外脲酶抑制潜力。
结果
在26种化合物中，17种表现出良好至显著的脲酶抑制活性，IC50值在49.93-351.46μM之间，与标准硫脲（IC50 = 21±0.11μM）相比。此外，所有化合物对正常3T3细胞系均无细胞毒性。
结论
本研究已确定β-酮砜为新型无细胞毒性的脲酶抑制剂。
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