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Carborane-Containing Hydroxamate MMP Ligands for the Treatment of Tumors Using Boron Neutron Capture Therapy (BNCT): Efficacy without Tumor Cell Entry.
Flieger, Sebastian; Takagaki, Mao; Kondo, Natsuko; Lutz, Marlon R; Gupta, Yash; Ueda, Hiroki; Sakurai, Yoshinori; Moran, Graham; Kempaiah, Prakasha; Hosmane, Narayan; Suzuki, Minoru; Becker, Daniel P.
Afiliación
  • Flieger S; Department of Chemistry and Biochemistry, Loyola University Chicago, Chicago, IL 60660, USA.
  • Takagaki M; Research Center for Nuclear Physics, Osaka University, 10-1 Mihoga-oka, Ibaraki-City 567-0047, Osaka, Japan.
  • Kondo N; Particle Radiation Oncology Research Center, Institute for Integrated Radiation and Nuclear Science, Kyoto University, 2-1010 Asashiro-Nishi, Kumatori, Sennan-gun 590-0494, Osaka, Japan.
  • Lutz MR; Department of Chemistry and Biochemistry, Loyola University Chicago, Chicago, IL 60660, USA.
  • Gupta Y; Department of Medicine, Infectious Diseases, Mayo Clinic, Jacksonville, FL 32224, USA.
  • Ueda H; Particle Radiation Oncology Research Center, Institute for Integrated Radiation and Nuclear Science, Kyoto University, 2-1010 Asashiro-Nishi, Kumatori, Sennan-gun 590-0494, Osaka, Japan.
  • Sakurai Y; Particle Radiation Oncology Research Center, Institute for Integrated Radiation and Nuclear Science, Kyoto University, 2-1010 Asashiro-Nishi, Kumatori, Sennan-gun 590-0494, Osaka, Japan.
  • Moran G; Department of Chemistry and Biochemistry, Loyola University Chicago, Chicago, IL 60660, USA.
  • Kempaiah P; Department of Medicine, Infectious Diseases, Mayo Clinic, Jacksonville, FL 32224, USA.
  • Hosmane N; Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, IL 60115, USA.
  • Suzuki M; Particle Radiation Oncology Research Center, Institute for Integrated Radiation and Nuclear Science, Kyoto University, 2-1010 Asashiro-Nishi, Kumatori, Sennan-gun 590-0494, Osaka, Japan.
  • Becker DP; Department of Chemistry and Biochemistry, Loyola University Chicago, Chicago, IL 60660, USA.
Int J Mol Sci ; 24(8)2023 Apr 09.
Article en En | MEDLINE | ID: mdl-37108137
New carborane-bearing hydroxamate matrix metalloproteinase (MMP) ligands have been synthesized for boron neutron capture therapy (BNCT) with nanomolar potency against MMP-2, -9 and -13. New analogs are based on MMP inhibitor CGS-23023A, and two previously reported MMP ligands 1 (B1) and 2 (B2) were studied in vitro for BNCT activity. The boronated MMP ligands 1 and 2 showed high in vitro tumoricidal effects in an in vitro BNCT assay, exhibiting IC50 values for 1 and 2 of 2.04 × 10-2 mg/mL and 2.67 × 10-2 mg/mL, respectively. The relative killing effect of 1 to L-boronophenylalanine (BPA) is 0.82/0.27 = 3.0, and that of 2 is 0.82/0.32 = 2.6, whereas the relative killing effect of 4 is comparable to boronophenylalanine (BPA). The survival fraction of 1 and 2 in a pre-incubation boron concentration at 0.143 ppm 10B and 0.101 ppm 10B, respectively, were similar, and these results suggest that 1 and 2 are actively accumulated through attachment to the Squamous cell carcinoma (SCC)VII cells. Compounds 1 and 2 very effectively killed glioma U87 delta EGFR cells after BNCT. This study is noteworthy in demonstrating BNCT efficacy through binding to MMP enzymes overexpressed at the surface of the tumor cell without tumor cell penetration.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia por Captura de Neutrón de Boro / Glioma Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia por Captura de Neutrón de Boro / Glioma Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza