Synthesis and Biological Evaluation of Carbonic Anhydrase III and IX Inhibitors using Gas Chromatography with Modified pH Sensitive Pellets

Q3 Pharmacology, Toxicology and Pharmaceutics

Jordan Journal of Pharmaceutical Sciences Pub Date : 2023-07-24 DOI:10.35516/jjps.v16i2.1470

Buthaina Hussein, Laurance M S Bourghli, Muhammed Alzweiri, Y. Al-Hiari, Mohammad Abu Sini, Soraya Alnabulsi, Batool Al-Ghwairi

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引用次数: 0

Abstract

Fifteen compounds were synthesized and tested as potential carbonic anhydrase III (CAIII) and carbonic anhydrase IX (CAIX) inhibitors, six of which are novel. Amides (a1-4), hydroxamic acids (b1-2), and imines (c1-9) derivatives were evaluated for their inhibitory activity against CAII and CAIX using gas chromatography with modified pH-sensitive pellets. The derivatives showed inhibition percentages between 12-56% for CAIII and 44-59% for CAIX, compared to 49% and 63% for captopril (the positive control), respectively. Imines showed the best inhibition of CAIII, while all derivatives showed comparable activity against CAIX. It is hypothesized that the nitrogen atom in imine, amide, or hydroxamic acid moieties in the vicinity of an ionizable group is in coordination with the zinc ion in the active site. Furthermore, the candidates were tested for their antimicrobial and antifungal activity. Generally, they showed low to zero activity against some gram-positive and negative bacteria. This supports the theory of their ability to bind to human carbonic anhydrase but not to bacterial one. These compounds could serve as useful scaffolds to develop more potent and selective carbonic anhydrase inhibitors as anti-obesity and anticancer candidates.

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改性pH敏感颗粒气相色谱法合成碳酸酐酶III和IX抑制剂及其生物学评价

合成并测试了15种化合物作为潜在的碳酸酐酶III（CAII）和碳酸酐酶IX（CAIX）抑制剂，其中6种是新的。酰胺（a1-4）、异羟肟酸（b1-2）和亚胺（c1-9）衍生物使用具有改性pH敏感颗粒的气相色谱法评估其对CAII和CAIX的抑制活性。衍生物对CAII的抑制率在12-56%和CAIX的抑制率为44-59%之间，而对卡托普利（阳性对照）的抑制率分别为49%和63%。亚胺对CAII表现出最好的抑制作用，而所有衍生物对CAIX都表现出相当的活性。假设可离子化基团附近的亚胺、酰胺或异羟肟酸部分中的氮原子与活性位点中的锌离子配位。此外，对候选药物的抗菌和抗真菌活性进行了测试。一般来说，它们对一些革兰氏阳性和阴性细菌显示出低至零的活性。这支持了它们与人类碳酸酐酶结合而不与细菌碳酸酐酶连接的理论。这些化合物可以作为有用的支架，开发更有效和选择性的碳酸酐酶抑制剂，作为抗肥胖和抗癌的候选药物。

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来源期刊

Jordan Journal of Pharmaceutical Sciences Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

CiteScore

1.70

自引率

0.00%

发文量

期刊介绍： The Jordan Journal of Pharmaceutical Sciences (JJPS) is a scientific, bi-annual, peer-reviewed publication that will focus on current topics of interest to the pharmaceutical community at large. Although the JJPS is intended to be of interest to pharmaceutical scientists, other healthy workers, and manufacturing processors will also find it most interesting and informative. Papers will cover basic pharmaceutical and applied research, scientific commentaries, as well as views, reviews. Topics on products will include manufacturing process, quality control, pharmaceutical engineering, pharmaceutical technology, and philosophies on all aspects of pharmaceutical sciences. The editorial advisory board would like to place an emphasis on new and innovative methods, technologies, and techniques for the pharmaceutical industry. The reader will find a broad range of important topics in this first issue.