Retini Michele, Järvinen Juulia, Bahrami Katayun, Tampio Janne, Bartoccini Francesca, Riihelä Petri, Pehkonen Henna, Värä Arina, Laitinen Tuomo, Huttunen Kristiina M, Rautio Jarkko, Piersanti Giovanni, Timonen Juri M
Department of Biomolecular Sciences, University of Urbino Carlo Bo, Piazza Rinascimento 6, 61029 Urbino, Italy.
School of Pharmacy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
ACS Med Chem Lett. 2024 Nov 11;15(12):2121-2128. doi: 10.1021/acsmedchemlett.4c00241. eCollection 2024 Dec 12.
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. 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.
本研究调查了硼化色氨酸作为癌症硼中子俘获疗法（BNCT）潜在硼递送剂的情况。我们采用简单且廉价的方法合成了5-和6-硼化色氨酸（ 和 ）的两种对映体。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，并与作为参考的L-硼代苯丙氨酸（L-BPA）进行了比较。为了确定这些色氨酸衍生物是否是大中性氨基酸转运蛋白1的底物，我们进行了分子动力学模拟以探索其转运机制。我们的研究结果揭示了癌细胞系之间硼化合物积累的差异，表明当临床使用的硼载体BPA无效时，色氨酸衍生物可作为有效的硼载体。
