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 (<b>1a</b> and <b>1b</b>) 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-<i>p</i>-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.
Authors
- Kristiina M. Huttunen (ORCID: https://orcid.org/0000-0002-1175-8517)
- Henna Pehkonen (ORCID: https://orcid.org/0000-0002-9615-384X)
- Michele Retini (ORCID: https://orcid.org/0000-0003-0218-8505)
- Francesca Bartoccini (ORCID: https://orcid.org/0000-0003-0400-7771)
- Juri M. Timonen
- Jarkko Rautio (ORCID: https://orcid.org/0000-0003-2172-3980)
- Katayun Bahrami (ORCID: https://orcid.org/0000-0002-3028-5663)
- Tuomo Laitinen (ORCID: https://orcid.org/0000-0003-1539-2142)
- Giovanni Piersanti (ORCID: https://orcid.org/0000-0003-0418-7143)
- Janne Tampio (ORCID: https://orcid.org/0000-0002-7526-0419)
- Juulia Järvinen (ORCID: https://orcid.org/0000-0002-5828-9367)
- Petri Riihelä
- Arina Värä
Institutions
- University of Helsinki (FI)
- University of Eastern Finland (FI)
- University of Urbino (IT)
Publication Details
- Journal
- ACS Medicinal Chemistry Letters
- Published
- 2024-11-11
- DOI
- https://doi.org/10.1021/acsmedchemlett.4c00241
- Citations
- 3
- Primary Topic
- Boron Compounds in Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 1.21
Funders
- European Commission
- Academy of Finland
- Suomen Kulttuurirahasto
- Päivikki ja Sakari Sohlbergin Säätiö
- China Scholarship Council
- Università degli Studi di Urbino Carlo Bo
- Biocenter Finland
- Suomalainen Konkordia-liitto
- Ministero dell'Università e della Ricerca
- European Social Fund