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

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 ( and ) 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--boronophenylalanine (l-BPA) as a reference.

Specific transport of temozolomide does not override DNA repair-mediated chemoresistance.

Temozolomide (TMZ) a DNA alkylating agent, is the standard-of-care for brain tumors, such as glioblastoma multiforme (GBM). Although the physicochemical and pharmacokinetic properties of TMZ, such as chemical stability and the ability to cross the blood-brain barrier (BBB), have been questioned in the past, the acquired chemoresistance has been the main limiting factor of long-term clinical use of TMZ. In the present study, an L-type amino acid transporter 1 (LAT1)-utilizing prodrug of TMZ (TMZ-AA, 6) was prepared and studied for its cellular accumulation and cytotoxic properties in human squamous cell carcinoma, UT-SCC-28 and UT-SCC-42B cells, and TMZ-sensitive human glioma, U-87MG cells that expressed functional LAT1.

Sweet Battle of the Epimers─Continued Exploration of Monosaccharide-Derived Delivery Agents for Boron Neutron Capture Therapy.

Boron neutron capture therapy (BNCT) is a cancer therapy in which boron delivery agents play a crucial role. In theory, delivery agents with high tumor targeting capabilities can lead to selective eradication of tumor cells without causing harmful side effects. We have been working on a GLUT1-targeting strategy to BNCT for a number of years and found multiple promising hit compounds which outperform the clinically employed boron delivery agents in vitro.

Structural Features Affecting the Interactions and Transportability of LAT1-Targeted Phenylalanine Drug Conjugates.

L-type amino acid transporter 1 (LAT1) transfers essential amino acids across cell membranes. Owing to its predominant expression in the blood-brain barrier and tumor cells, LAT1 has been exploited for drug delivery and targeting to the central nervous system (CNS) and various cancers. Although the interactions of amino acids and their mimicking compounds with LAT1 have been extensively investigated, the specific structural features for an optimal drug scaffold have not yet been determined.

Development of Sesamol Carbamate-L-Phenylalanine Prodrug Targeting L-Type Amino Acid Transporter1 (LAT1) as a Potential Antiproliferative Agent against Melanoma.

Sesamol is a compound reported to have anti-melanogenesis and anti-melanoma actions. Sesamol, however, has low intracellular drug concentration and fast excretion, which can limit its benefits in the clinic. To overcome this drawback and increase intracellular delivery of sesamol into the target melanoma, research has focused on L-type amino acid transporter 1 (LAT1)-mediated prodrug delivery into melanoma cells.