Some pyrroles as inhibitors of the pentose phosphate pathways enzymes: An in vitro and molecular docking study

IF 2.3 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Molecular Recognition Pub Date : 2024-03-21 DOI:10.1002/jmr.3083

Muhammet Serhat Özaslan

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引用次数: 0

Abstract

Glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) are pentose phosphate pathway enzymes. Compounds with a heterocyclic pyrrole ring system containing this atom can be derivatized with various functional groups into highly effective bioactive agents. In this study, pyrrole derivatives on these enzyme's activity were investigated. The IC₅₀ values of different concentrations of pyrrole derivatives for G6PD were found in the range of 0.022–0.221 mM K_i values 0.021 ± 0.003–0.177 ± 0.021 and for 6PGD IC₅₀ values 0.020–0.147, mM K_i values 0.013 ± 0.002–0.113 ± 0.030 mM. The 2-acetyl-1-methylpyrrole (1g) showed the best inhibition value for G6PD and 6PGD enzymes. In addition, in silico molecular docking experiments were performed to elucidate how these pyrrole derivatives (1a–g) interact with the binding sites of the target enzymes. The study's findings on pyrrole derivatives could be used to create innovative therapeutics that could be a treatment for many diseases, especially cancer manifestations.

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一些吡咯类化合物作为磷酸戊糖途径酶的抑制剂：体外和分子对接研究。

葡萄糖-6-磷酸脱氢酶（G6PD）和葡萄糖-6-磷酸脱氢酶（6PGD）是磷酸戊糖途径酶。含有该原子的杂环吡咯环系统化合物可以用各种官能团衍生成高效的生物活性剂。本研究调查了吡咯衍生物对这些酶活性的影响。不同浓度的吡咯衍生物对 G6PD 的 IC50 值范围为 0.022-0.221 mM Ki 值为 0.021 ± 0.003-0.177 ± 0.021，对 6PGD 的 IC50 值为 0.020-0.147 mM Ki 值为 0.013 ± 0.002-0.113 ± 0.030 mM。2-acetyl-1-methylpyrrole (1g) 对 G6PD 和 6PGD 酶的抑制值最佳。此外，还进行了硅学分子对接实验，以阐明这些吡咯衍生物（1a-g）如何与目标酶的结合位点相互作用。这项关于吡咯衍生物的研究成果可用于开发创新疗法，治疗多种疾病，尤其是癌症。

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来源期刊

Journal of Molecular Recognition 生物-生化与分子生物学

CiteScore

4.60

自引率

3.70%

发文量

审稿时长

2.7 months

期刊介绍： Journal of Molecular Recognition (JMR) publishes original research papers and reviews describing substantial advances in our understanding of molecular recognition phenomena in life sciences, covering all aspects from biochemistry, molecular biology, medicine, and biophysics. The research may employ experimental, theoretical and/or computational approaches. The focus of the journal is on recognition phenomena involving biomolecules and their biological / biochemical partners rather than on the recognition of metal ions or inorganic compounds. Molecular recognition involves non-covalent specific interactions between two or more biological molecules, molecular aggregates, cellular modules or organelles, as exemplified by receptor-ligand, antigen-antibody, nucleic acid-protein, sugar-lectin, to mention just a few of the possible interactions. The journal invites manuscripts that aim to achieve a complete description of molecular recognition mechanisms between well-characterized biomolecules in terms of structure, dynamics and biological activity. Such studies may help the future development of new drugs and vaccines, although the experimental testing of new drugs and vaccines falls outside the scope of the journal. Manuscripts that describe the application of standard approaches and techniques to design or model new molecular entities or to describe interactions between biomolecules, but do not provide new insights into molecular recognition processes will not be considered. Similarly, manuscripts involving biomolecules uncharacterized at the sequence level (e.g. calf thymus DNA) will not be considered.