Design of the New Closo-Dodecarborate-Containing Gemcitabine Analogue for the Albumin-Based Theranostics Composition.

Content Provider	Europe PMC
Author	Raskolupova, Valeria I. Wang, Meiling Dymova, Maya A. Petrov, Gleb O. Shchudlo, Ivan M. Taskaev, Sergey Yu. Abramova, Tatyana V. Godovikova, Tatyana S. Silnikov, Vladimir N. Popova, Tatyana V.
Editor	da Silva, Fernando de Carvalho Ferreira, Vitor Francisco Forezi, Luana Da Silva Magalhães
Copyright Year	2023
Abstract	Combination therapy is becoming an increasingly important treatment strategy because multi-drugs can maximize therapeutic effect and overcome potential mechanisms of drug resistance. A new albumin-based theranostic containing gemcitabine closo-dodecaborate analogue has been developed for combining boron neutron capture therapy (BNCT) and chemotheraphy. An exo-heterocyclic amino group of gemcitabine was used to introduce closo-dodecaborate, and a 5'-hydroxy group was used to tether maleimide moiety through an acid-labile phosphamide linker. The N-trifluoroacylated homocysteine thiolactone was used to attach the gemcitabine analogue to human serum albumin (HSA) bearing Cy5 or Cy7 fluorescent dyes. The half-maximal inhibitory concentration (IC50) of the designed theranostic relative to T98G cells was 0.47 mM with the correlation coefficient R = 0.82. BNCT experiments resulted in a decrease in the viability of T98G cells, and the survival fraction was ≈ 0.4.
Journal	Molecules
Volume Number	28
DOI	10.3390/molecules28062672
PubMed Central reference number	PMC10056911
Issue Number	6
PubMed reference number	36985644
e-ISSN	14203049
Language	English
Publisher	Molecular Diversity Preservation International (MDPI)
Publisher Date	2023-03-15
Access Restriction	Open
Subject Keyword	boron neutron capture therapy boron delivery agents gemcitabine analogue boronated albumin theranostic conjugate cell viability and proliferation clonogenic assay
Content Type	Text
Resource Type	Article
Subject	Physical and Theoretical Chemistry Medicine Chemistry Drug Discovery Pharmaceutical Science Analytical Chemistry Molecular Medicine Organic Chemistry