Xiaoping Tang

Glycosylated diazeniumdiolates: a novel class of enzyme-activated nitric oxide donors

Abstract Synthetic procedures have been developed to attach the nitric oxide releasing diazeniumdiolate functional groups [N(O)NO] − to a carbohydrate unit. These glycosylated diazeniumdiolates exhibited significantly improved stability as compared to their parent diazeniumdiolate salts, yet they could readily release nitric oxide upon activation by glycosidases. Preliminary antitumor screen assay demonstrated that this class of compounds had antitumor activity.

Synthesis of peptide-diazeniumdiolate conjugates: towards enzyme activated antitumor agents

Abstract The development of NO donors with site-specific and time-controlled properties is of great interest. We have designed a novel prodrug class as possible agents against metastatic prostate cancer by coupling a diazeniumdiolate to the terminal carboxyl groups of amino acids or peptides, such as Ser-Ser-Tyr-Tyr, Ser-Ser-Phe-Tyr, and Gly-Ile-Ser-Ser-Phe-Tyr. These prodrugs can be activated by α-chymotrypsin or prostate specific antigen and are potentially potent compounds for prostatic cancer.

Synthesis of beta-Lactamase activated nitric oxide donors

In order to achieve site specific delivery of NO, we designed conjugates of cephalosporin with NO donors. NO donors such as cupferron and SIN-1 were evaluated as potential choices for conjugates. Cephalosporin conjugated with SIN-1 demonstrated promising beta-lactamase dependent NO releasing ability.

N-hydroxyl derivatives of guanidine based drugs as enzymatic NO donors.

Recent research suggests that NO may play a role in the physiological effects of some guanidine-containing drugs. In this report, three guanidine-containing drugs (guanadrel, guanoxan, and guanethidine) together with their N-hydroxyl derivatives were synthesized and their NO-releasing abilities catalyzed by nitric oxide synthases (NOSs) and horseradish peroxidase were evaluated. The guanidine containing compounds could not release NO in the presence of NOS or peroxidase. The corresponding N-hydroxyl compounds exhibited weak NO-releasing ability under the catalyzed of NOS and good NO-releasing ability under the oxidation by horseradish peroxidase in the presence of H(2)O(2). These compounds also displayed vasodilatory activity.

Synthesis and cytotoxicities of mannose conjugated S-Nitroso-N-acetylpenicillamine (SNAP)

A series of mannose conjugated S-nitroso-N-acetylpenicillamines (SNAPs) has been synthesized, and their cytotoxicities were assessed for DU 145 human prostate cancer cells and Hela R cancer cells.