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

ACS Medicinal Chemistry Letters Pub Date : 2024-11-11 DOI:10.1021/acsmedchemlett.4c0024110.1021/acsmedchemlett.4c00241

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.

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来源期刊

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.