Asymmetric Synthesis and Biological Evaluation of Both Enantiomers of 5- and 6-Boronotryptophan as Potential Boron Delivery Agents for Boron Neutron Capture Therapy

IF 3.5 3区 医学 Q2 CHEMISTRY, MEDICINAL
Michele Retini, Juulia Järvinen, Katayun Bahrami, Janne Tampio, Francesca Bartoccini, Petri Riihelä, Henna Pehkonen, Arina Värä, Tuomo Laitinen, Kristiina M. Huttunen, Jarkko Rautio, Giovanni Piersanti and Juri M. Timonen*, 
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引用次数: 0

Abstract

This research investigates boronated tryptophans as potential boron delivery agents for boron neutron capture therapy (BNCT) of cancer. We synthesized both enantiomers of 5- and 6-boronotryptophans (1a and 1b) using simple and inexpensive methods. Their uptake was assessed in two human cancer cell lines, CAL27 (head and neck cancer) and U87-MG (brain cancer), and compared to l-p-boronophenylalanine (l-BPA) as a reference. To determine whether these tryptophan derivatives are substrates for large amino acid transporter 1, we performed molecular dynamics simulations to explore their transport mechanism. Our findings reveal differences in boron compound accumulation between the cancer cell lines, indicating that tryptophan derivatives could serve as effective boron carriers when the clinically used boron carrier, BPA, is ineffective.

5-和6-硼色氨酸对映体作为硼中子俘获治疗硼递送剂的不对称合成和生物学评价
本研究探讨硼化色氨酸作为硼中子俘获治疗(BNCT)的潜在硼递送剂。我们用简单和廉价的方法合成了5-和6-硼色氨酸对映体(1a和1b)。在两种人类癌细胞系CAL27(头颈癌)和U87-MG(脑癌)中评估了它们的摄取情况,并将其与l-对硼苯丙氨酸(l-BPA)作为对照。为了确定这些色氨酸衍生物是否是大氨基酸转运体1的底物,我们进行了分子动力学模拟来探索它们的转运机制。我们的研究结果揭示了不同癌细胞系之间硼化合物积累的差异,表明色氨酸衍生物可以作为有效的硼载体,而临床上使用的硼载体BPA无效。
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来源期刊
ACS Medicinal Chemistry Letters
ACS Medicinal Chemistry Letters CHEMISTRY, MEDICINAL-
CiteScore
7.30
自引率
2.40%
发文量
328
审稿时长
1 months
期刊介绍: ACS Medicinal Chemistry Letters is interested in receiving manuscripts that discuss various aspects of medicinal chemistry. The journal will publish studies that pertain to a broad range of subject matter, including compound design and optimization, biological evaluation, drug delivery, imaging agents, and pharmacology of both small and large bioactive molecules. Specific areas include but are not limited to: Identification, synthesis, and optimization of lead biologically active molecules and drugs (small molecules and biologics) Biological characterization of new molecular entities in the context of drug discovery Computational, cheminformatics, and structural studies for the identification or SAR analysis of bioactive molecules, ligands and their targets, etc. Novel and improved methodologies, including radiation biochemistry, with broad application to medicinal chemistry Discovery technologies for biologically active molecules from both synthetic and natural (plant and other) sources Pharmacokinetic/pharmacodynamic studies that address mechanisms underlying drug disposition and response Pharmacogenetic and pharmacogenomic studies used to enhance drug design and the translation of medicinal chemistry into the clinic Mechanistic drug metabolism and regulation of metabolic enzyme gene expression Chemistry patents relevant to the medicinal chemistry field.
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