Tachihara, Yoshihiro published the artcileMechanically interlocked molecular architectures of valinomycin as cancer targeted prodrugs, Category: catalysis-chemistry, the publication is Nano Select (2022), 3(8), 1242-1251, database is CAplus.
Macrocyclic drugs are promising agents for treating a variety of diseases. However, these compounds usually present delivery limitations, such as low tissue selectivity and poor cellular uptake, which may impair efficacy and clin. translation. Here, we propose a mol. machine approach for delivering macrocyclic drugs based on their assembly into bioactive rotaxanes. To prove this concept, we use the extremely toxic macrocycle valinomycin (Val) as the host mol., and identify dihydralazine (Dihyd) as a guest mol. after screening several guest compounds The Val-Dihyd complex is mech. interlocked by capping one hydrazide group in Dihyd with fluorescein isothiocyanate (FITC) and the other with a Y-shape branched poly(ethylene glycol) (PEG) via a pH-sensitive hydrazone bond. Thus, the Val-loaded rotaxanes (Vrot) are stable at physiol. pH, but release Val at mild acidic conditions mimicking intratumoral and endosomal environments. In vitro studies revealed Vrot is less cytotoxic than free Val in pancreatic cancer cells, while modifying Vrot with cyclic arginine-glycine-aspartic acid (cRGD) peptides promotes the cytotoxicity by enhancing cellular uptake. These results indicate the potential of rotaxanes of macrocyclic drugs for generating cancer targeted prodrugs.
Nano Select published new progress about 1395786-30-7. 1395786-30-7 belongs to catalysis-chemistry, auxiliary class Inhibitor, name is Dbco-maleimide, and the molecular formula is C4Br2N2O4S, Category: catalysis-chemistry.
Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia