An activatable prodrug for the treatment of metastatic tumors.

Metastatic cancers have historically been difficult to treat. However, metastatic tumors have been found to have high levels of reactive oxygen species such as hydrogen peroxide (H2O2), supporting the hypothesis that a prodrug could be activated by intracellular H2O2 and lead to a potential antimetastatic therapy. In this study, prodrug 7 was designed to be activated by H2O2-mediated boronate oxidation, resulting in activation of the fluorophore for detection and release of the therapeutic agent, SN-38.

An activatable theranostic for targeted cancer therapy and imaging.

A new theranostic strategy is described. It is based on the use of an "all in one" prodrug, namely the biotinylated piperazine-rhodol conjugate 4 a. This conjugate, which incorporates the anticancer drug SN-38, undergoes self-immolative cleavage when exposed to biological thiols.

Rational design of biotin-disulfide-coumarin conjugates: a cancer targeted thiol probe and bioimaging.

Biotin-disulfide-coumarin conjugates are designed and synthesized as novel fluorescent sensors for cancer targeted intracellular thiol imaging in living organisms. In vitro experiments disclose that probe 6 is preferentially taken up by biotin receptor-positive A549 tumor cells through receptor mediated endocytosis.

A fluorescence off-on reporter for real time monitoring of gemcitabine delivery to the cancer cells.

We present the design, synthesis, optical properties and in vitro biological assessments of the theranostic prodrug in which a near IR fluorophore is conjugated with a cancer cell-directing biotin unit; further it is linked with the anti-cancer drug gemcitabine via a self-immolative spacer, a disulfide bond. The prodrug is able to monitor drug delivery and cellular imaging.

Gemcitabine-coumarin-biotin conjugates: a target specific theranostic anticancer prodrug.

We present here, the design, synthesis, spectroscopic characterization, and in vitro biological assessment of a gemcitabine-coumarin-biotin conjugate (5). Probe 5 is a multifunctional molecule composed of a thiol-specific cleavable disulfide bond, a coumarin moiety as a fluorescent reporter, gemcitabine (GMC) as a model active drug, and biotin as a cancer-targeting unit. Upon addition of free thiols that are relatively abundant in tumor cells, disulfide bond cleavage occurs as well as active drug GMC release and concomitantly fluorescence intensity increases.

Iron-catalyzed synthesis of functionalized 2H-chromenes via intramolecular alkyne-carbonyl metathesis.

An iron-catalyzed intramolecular alkyne-aldehyde metathesis strategy of the alkynyl ether of salicylaldehyde derivatives has been developed which works under mild reaction conditions to produce the functionalized 2H-chromene derivatives. This protocol is compatible toward a wide range of functional groups, such as methoxy, fluoro, chloro, bromo, and phenyl groups. This method provides an atom-economical and environmentally friendly approach for the synthesis of a series of substituted 2H-chromenes.

Iron(III)-catalyzed four-component coupling reaction of 1,3-dicarbonyl compounds, amines, aldehydes, and nitroalkanes: a simple and direct synthesis of functionalized pyrroles.

A simple, convenient, and multicomponent coupling strategy for the synthesis of highly functionalized pyrroles catalyzed by iron(III) salts has been developed. This strategy demonstrated four-component coupling reactions of 1,3-dicarbonyl compounds, amines, aromatic aldehydes, and nitroalkanes without an inert atmosphere. This methodology provides an alternative approach for easy access of highly substituted pyrroles in moderate to very good yields using four simple and readily available building blocks via one-pot tandem reaction.