基于 3-功能化苯磺酰胺的 1,3,4-噁二唑类化合物作为选择性碳酸酐酶 XIII 抑制剂的设计、合成与生物评价。
3-Functionalised benzenesulphonamide based 1,3,4-oxadiazoles as selective carbonic anhydrase XIII inhibitors: Design, synthesis and biological evaluation.
机构信息
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad 500037, India.
Università degli Studi di Firenze, Neurofarba Dept., Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
出版信息
Bioorg Med Chem Lett. 2021 Apr 1;37:127856. doi: 10.1016/j.bmcl.2021.127856. Epub 2021 Feb 18.
A new series of benzenesulphonamide linked-1,3,4-oxadiazole hybrids (6a-s) has been synthesized and tested for their carbonic anhydrase inhibition against human (h) carbonic anhydrase (CA) isoforms hCA I, II, IX, and XIII. Fluorescence properties of some of the synthesized molecules were studied. Most of the molecules exhibited significant inhibitory power, comparable or better than the standard drug acetazolamide (AAZ) on hCA XIII. Out of 19 tested molecules, compound 6e (75.8 nM) was 3 times more potent than AAZ (250.0 nM) against hCA I, whereas compound 6e (15.4 nM), 6g (16.2 nM), 6h (16.4 nM) and 6i (17.0 nM) were found to be more potent than AAZ (17.0 nM) against isoform hCA XIII. It is anticipated that these compounds could be taken as the potential leads for the development of selective hCA XIII isoform inhibitors with improved potency.
已合成了一系列新的苯磺酰胺连接 1,3,4-噁二唑杂合化合物（6a-s），并对其进行了碳酸酐酶抑制活性测试，以评估其对人源碳酸酐酶（hCA）同工型 hCA I、II、IX 和 XIII 的抑制作用。研究了部分合成分子的荧光性质。大多数分子表现出显著的抑制能力，与标准药物乙酰唑胺（AAZ）相比，对 hCA XIII 的抑制作用相当或更好。在所测试的 19 种分子中，化合物 6e（75.8 nM）对 hCA I 的抑制活性比 AAZ（250.0 nM）强 3 倍，而化合物 6e（15.4 nM）、6g（16.2 nM）、6h（16.4 nM）和 6i（17.0 nM）对 hCA XIII 的抑制活性则优于 AAZ（17.0 nM）。这些化合物有望成为开发具有更高活性的选择性 hCA XIII 同工型抑制剂的潜在先导化合物。
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