We examined the concept of a novel prodrug strategy in which anticancer drug can be locally released by visible/near IR light, taking advantage of the photodynamic process and photo-unclick chemistry. Our most recently formulated prodrug of combretastatin A-4, Pc-(L-CA4)2, showed multifunctionality for fluorescence imaging, light-activated drug release, and the combined effects of PDT and local...

The peptidyl prodrug (1S,2S,5R,6S)-2-[(2'S)-(2-Amino)propionyl]a-minobicyclo[3.1.0.]hexen-2,6-dicarboxylic acid, also known as LY544344, was discovered to improve the oral bioavailability of the parent drug (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740), a potent group II metabotropic glutamate receptor agonist. This prodrug has been shown to deliver high plasma concentrations...

Intoroduction Prodrug approach deals with chemical biotransformation or enzymatic conversion or involves inactive or less active bio-reversible derivatives of active drug molecules. They have to pass through enzymatic or chemical biotransformation before eliciting their pharmacological action. Methods & Materials The two different pharmacophores combine to give synergistic activity or may hel...

In antibody-directed enzyme prodrug therapy, an enzyme conjugated to an antitumor antibody is given i.v. and localizes in the tumor. A prodrug is then given, which is converted to a cytotoxic drug selectively in the tumor. Ten patients with colorectal carcinoma expressing carcinoembryonic antigen received antibody-directed enzyme prodrug therapy with A5B7 F(ab*)2 antibody to carcinoembryonic an...

DFT calculation results for intramolecular proton transfer reactions in Kirby's enzyme models 1-7 reveal that the reaction rate is quite responsive to geometric disposition, especially to distance between the two reactive centers, r (GM), and the angle of attack, α (the hydrogen bonding angle). Hence, the study on the systems reported herein could provide a good basis for designing aza nucleosi...

Theoretically, prodrugs are relatively noncytotoxic molecules, capable of being converted to cytotoxic species only at the site of the tumor, affording enhanced antitumor selectivity. One approach aimed at enhancing the selectivity of cancer chemotherapy for solid tumors relies on the application of prodrug-activating systems in suicide gene therapy. Enzyme-activating prodrug therapy, also know...

Bisphosphonates are used clinically to treat disorders of calcium metabolism and malignant bone disease and are known to inhibit cancer cell growth, adhesion, and invasion. However, clinical use of these agents for the treatment of extraskeletal disease is limited because of low cell permeability. We recently described a bisphosphonamidate prodrug strategy for efficient intracellular release of...

It is estimated that about 10% of the drugs approved worldwide can be classified as prodrugs. Prodrugs, which have no or poor biological activity, are chemically modified versions of a pharmacologically active agent, which must undergo transformation in vivo to release the active drug. They are designed in order to improve the physicochemical, biopharmaceutical and/or pharmacokinetic properties...

We developed the novel polymeric prodrugs synthesized by mechanochemical solid-state copolymerization of glucose-based polysaccharides (dextran orglycogen) and the methacryloyloxy derivative of 5-fluorouracil (5-FU). The copolymerization proceededreadily and each polymeric prodrug was quantitatively obtained within8 h reaction. The number average molecular weight (Mn) and polydispersity (H) of ...

Background Prodrug-activator gene therapy with Toca 511, a tumor-selective retroviral replicating vector (RRV) encoding yeast cytosine deaminase, is being evaluated in recurrent high-grade glioma patients. Nonlytic retroviral infection leads to permanent integration of RRV into the cancer cell genome, converting infected cancer cell and progeny into stable vector producer cells, enabling ongoin...