当前位置：
X-MOL 学术
›
Chem. Bio. Drug Des.
›
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.)
Synthesis, molecular modeling, and biological evaluation of 4‐[5‐aryl‐3‐(thiophen‐2‐yl)‐4,5‐dihydro‐1H‐pyrazol‐1‐yl] benzenesulfonamides toward acetylcholinesterase, carbonic anhydrase I and II enzymes
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2017-12-04 , DOI: 10.1111/cbdd.13149 Cem Yamali 1 , Halise Inci Gul 1 , Abdulilah Ece 2 , Parham Taslimi 3 , Ilhami Gulcin 3
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2017-12-04 , DOI: 10.1111/cbdd.13149 Cem Yamali 1 , Halise Inci Gul 1 , Abdulilah Ece 2 , Parham Taslimi 3 , Ilhami Gulcin 3
Affiliation
|
In this study, 4‐[5‐aryl‐3‐(thiophen‐2‐yl)‐4,5‐dihydro‐1H‐pyrazol‐1‐yl] benzenesulfonamides were synthesized, and inhibition effects on AChE, hCA I, and hCA II were evaluated. Ki values of the compounds toward hCA I were in the range of 24.2 ± 4.6‐49.8 ± 12.8 nm, while they were in the range of 37.3 ± 9.0‐65.3 ± 16.7 nm toward hCA II. Ki values of the acetazolamide were 282.1 ± 19.7 nm and 103.60 ± 27.6 nm toward both isoenzymes, respectively. The compounds inhibited AChE with Ki in the range of 22.7 ± 10.3‐109.1 ± 27.0 nm, whereas the tacrine had Ki value of 66.5 ± 13.8 nm. Electronic structure calculations at M06‐L/6‐31 + G(d,p)//AM1 level and molecular docking studies were also performed to enlighten inhibition mechanism and to support experimental findings. Results obtained from calculations of molecular properties showed that the compounds obey drug‐likeness properties. The experimental and computational findings obtained in this study might be useful in the design of novel inhibitors against hCA I, hCA II, and AChE.
中文翻译：
4-[5-芳基-3-(噻吩-2-基)-4,5-二氢-1H-吡唑-1-基]苯磺酰胺对乙酰胆碱酯酶、碳酸酐酶 I 和 II 的合成、分子建模和生物学评价
本研究合成了4-[5-芳基-3-(噻吩-2-基)-4,5-二氢-1H-吡唑-1-基]苯磺酰胺类化合物，并对AChE、hCA I和对 hCA II 进行了评估。化合物对 hCA I 的K i 值在 24.2 ± 4.6‐49.8 ± 12.8 nm范围内，而对 hCA II 的 K i值在 37.3 ± 9.0‐65.3 ± 16.7 nm范围内。两种同工酶的乙酰唑酰胺的K i值分别为 282.1 ± 19.7 nm和 103.60 ± 27.6 nm 。这些化合物抑制 AChE 的K i范围为 22.7 ± 10.3‐109.1 ± 27.0 nm ，而他克林的K i值为 66.5 ± 13.8 nm 。还进行了 M06-L/6-31 + G(d,p)//AM1 水平的电子结构计算和分子对接研究，以启发抑制机制并支持实验结果。分子性质的计算结果表明，这些化合物具有药物相似性。本研究中获得的实验和计算结果可能有助于设计新型 hCA I、hCA II 和 AChE 抑制剂。
更新日期：2017-12-04
中文翻译：
4-[5-芳基-3-(噻吩-2-基)-4,5-二氢-1H-吡唑-1-基]苯磺酰胺对乙酰胆碱酯酶、碳酸酐酶 I 和 II 的合成、分子建模和生物学评价
本研究合成了4-[5-芳基-3-(噻吩-2-基)-4,5-二氢-1H-吡唑-1-基]苯磺酰胺类化合物，并对AChE、hCA I和对 hCA II 进行了评估。化合物对 hCA I 的K i 值在 24.2 ± 4.6‐49.8 ± 12.8 nm范围内，而对 hCA II 的 K i值在 37.3 ± 9.0‐65.3 ± 16.7 nm范围内。两种同工酶的乙酰唑酰胺的K i值分别为 282.1 ± 19.7 nm和 103.60 ± 27.6 nm 。这些化合物抑制 AChE 的K i范围为 22.7 ± 10.3‐109.1 ± 27.0 nm ，而他克林的K i值为 66.5 ± 13.8 nm 。还进行了 M06-L/6-31 + G(d,p)//AM1 水平的电子结构计算和分子对接研究，以启发抑制机制并支持实验结果。分子性质的计算结果表明，这些化合物具有药物相似性。本研究中获得的实验和计算结果可能有助于设计新型 hCA I、hCA II 和 AChE 抑制剂。
京公网安备 11010802027423号