黄连木类黄酮2-(3,4-二羟基苯基)-7,8-二羟基-3-甲氧基铬-4-酮抑制外核苷酸焦磷酸酶/磷酸二酯酶1 (ENPP1)的研究

Q3 Chemistry Chemistry Pub Date : 2023-09-30 DOI:10.3390/chemistry5040142
Abdur Rauf, Zuneera Akram, Muhammad Naveed, Najla AlMasoud, Taghrid S. Alomar, Muhammad Saleem, Abdul Waheed, Giovanni Ribaudo
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引用次数: 0

摘要

外核苷酸焦磷酸酶/磷酸二酯酶1 (ENPP1)通过水解核苷酸三磷酸和环核苷酸调节骨骼和软组织矿化,并参与免疫系统的调节。事实上,ENPP1降解了2 ',3 ' -环GMP-AMP二核苷酸(2 ',3 ' -cGAMP),后者是干扰素基因表面受体刺激剂(STING)的激动剂,从而下调免疫反应。因此,ENPP1抑制剂正在被研究作为感染和癌症的佐剂。黄连木是一种具有多种生物活性和传统用途的药用植物。在本研究中,我们报道了从中国紫杉树树皮甲醇提取物中分离到transilitin(2-(3,4-二羟基苯基)-7,8-二羟基-3-甲氧基铬-4-one)并对其作为ENPP1抑制剂的活性进行了研究。该化合物对与ENPP1结构相关的蛇毒磷酸二酯酶具有剂量依赖性抑制作用。此外,利用分子模型研究评估了transilitin与大分子靶标的结合基序。我们的研究结果通过揭示其生物学作用的机制,支持了紫荆及其提取物的传统医学应用。
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Studies on the Inhibition of Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1) by 2-(3,4-Dihydroxyphenyl)-7,8-dihydroxy-3-methoxychromen-4-one, a Flavonoid from Pistacia chinensis
Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) regulates skeletal and soft tissue mineralization by hydrolyzing nucleotide triphosphates and cyclic nucleotides, and is involved in the modulation of immune system. In fact, ENPP1 degrades 2′,3′-cyclic GMP-AMP dinucleotide (2′,3′-cGAMP), which is an agonist of surface receptor stimulator of interferon genes (STING), thus downregulating immune response. Consequently, ENPP1 inhibitors are being studied as adjuvant agents in infections and cancer. Pistacia chinensis is a medicinal plant endowed with several biological activities and traditional uses. In the current study, we report the isolation of transilitin (2-(3,4-dihydroxyphenyl)-7,8-dihydroxy-3-methoxychromen-4-one) from the methanolic extract of P. chinensis barks and the investigation of its activity as ENPP1 inhibitor. The compound was tested in vitro against snake venom phosphodiesterase, which is structurally related to ENPP1, and dose-dependently inhibited the enzyme. Moreover, molecular modeling studies were employed to assess the binding motif of the transilitin with the macromolecular target. Our findings support the traditional medical application of P. chinensis and its extracts by shedding new light on the mechanisms underlying their biological action.
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CiteScore
2.50
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11 weeks
期刊介绍: Chemistry—A European Journal is a truly international journal with top quality contributions (2017 ISI Impact Factor: 5.16). It publishes a wide range of outstanding Reviews, Minireviews, Concepts, Full Papers, and Communications from all areas of chemistry and related fields.
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