58006-32-9Relevant articles and documents
Exploring the Biochemical Foundations of a Successful GLUT1-Targeting Strategy to BNCT: Chemical Synthesis and in Vitro Evaluation of the Entire Positional Isomer Library of ortho-Carboranylmethyl-Bearing Glucoconjugates
Matovi?, Jelena,J?rvinen, Juulia,Sokka, Iris K.,Imlimthan, Surachet,Raitanen, Jan-Erik,Montaser, Ahmed,Maaheimo, Hannu,Huttunen, Kristiina M.,Per?niemi, Sirpa,Airaksinen, Anu J.,Sarparanta, Mirkka,Johansson, Mikael P.,Rautio, Jarkko,Ekholm, Filip S.
, p. 285 - 304 (2020/12/21)
Boron neutron capture therapy (BNCT) is a noninvasive binary therapeutic modality applicable to the treatment of cancers. While BNCT offers a tumor-targeting selectivity that is difficult to match by other means, the last obstacles preventing the full har
Synthesis of Bradyrhizose from d -Glucose
Ngoje, Philemon,Crich, David
supporting information, p. 523 - 527 (2020/01/21)
We describe the synthesis of the unusual bicyclic sugar bradyrhizose in 14 steps and a 6% overall yield from d-glucose. The synthesis involves the elaboration of a trans-fused carbocyclic ring onto the preexisting glucopyranose framework followed by adjus
Chemical Approach to Positional Isomers of Glucose-Platinum Conjugates Reveals Specific Cancer Targeting through Glucose-Transporter-Mediated Uptake in Vitro and in Vivo
Patra, Malay,Awuah, Samuel G.,Lippard, Stephen J.
supporting information, p. 12541 - 12551 (2016/10/07)
Glycoconjugation is a promising strategy for specific targeting of cancer. In this study, we investigated the effect of d-glucose substitution position on the biological activity of glucose-platinum conjugates (Glc-Pts). We synthesized and characterized all possible positional isomers (C1α, C1β, C2, C3, C4, and C6) of a Glc-Pt. The synthetic routes presented here could, in principle, be extended to prepare glucose conjugates with different active ingredients, other than platinum. The biological activities of the compounds were evaluated both in vitro and in vivo. We discovered that varying the position of substitution of d-glucose alters not only the cellular uptake and cytotoxicity profile but also the GLUT1 specificity of resulting glycoconjugates, where GLUT1 is glucose transporter 1. The C1α- and C2-substituted Glc-Pts (1α and 2) accumulate in cancer cells most efficiently compared to the others, whereas the C3-Glc-Pt (3) is taken up least efficiently. Compounds 1α and 2 are more potent compared to 3 in DU145 cells. The α- and β-anomers of the C1-Glc-Pt also differ significantly in their cellular uptake and activity profiles. No significant differences in uptake of the Glc-Pts were observed in non-cancerous RWPE2 cells. The GLUT1 specificity of the Glc-Pts was evaluated by determining the cellular uptake in the absence and in the presence of the GLUT1 inhibitor cytochalasin B, and by comparing their anticancer activity in DU145 cells and a GLUT1 knockdown cell line. The results reveal that C2-substituted Glc-Pt 2 has the highest GLUT1-specific internalization, which also reflects the best cancer-targeting ability. In a syngeneic breast cancer mouse model overexpressing GLUT1, compound 2 showed antitumor efficacy and selective uptake in tumors with no observable toxicity. This study thus reveals the synthesis of all positional isomers of d-glucose substitution for platinum warheads with detailed glycotargeting characterization in cancer.
