Bioreductive prodrugs for cancer therapy springerlink. A novel design strategy for stable metal complexes of. This article also describes novel approaches where hapbased. These hypoxiaactivated prodrugs can target and kill hypoxic cells, and their effect can extend to include sterilization of surrounding tumor cells when the activated metabolites are sufficiently stable to diffuse beyond their primary site of action.
Clinical advances of hypoxiaactivated prodrugs in combination. Pdf clinical advances of hypoxiaactivated prodrugs in. Bioreductive drugs are targeted to the underoxygenated region of the tumor through activation by specific reductases associated with hypoxia 71. Reduction to a less stable complex can free the active drug. Apaziquone odac briefing book 6 figure 19 odds ratios 95% ci for 2year recurrence rate and hazard ratios 95%.
Many solid tumours are inefficient in the development of their own blood supply, resulting in hypoxic regions within the tumour cell population. Most drugs fit into one or more of the following categories. Pdf with the increasing incidence of cancer worldwide, the need for specific. Bioreductive drugs, as an adjunct to any cancer treatment, could potentially fulfil this need. Pdf in designing of prodrugs, targeting can be achieved in two ways. Polyamine mustards are candidates for conversion into hypoxiaselective prodrugs via complexation with metals. Therefore, the combination of radiotherapy and bioreductive drugs presents an. A bioreductive prodrug of cucurbitacin b significantly. Synthesis of novel paclitaxel prodrugs designed for.
This bioreductive prodrug could be cleaved rapidly releasing the ptxdipeptide, and then degraded to liberate ptx as a final cleavage product within a few hours in prostate tumor tissue. Pdf therapeutic potential of prodrugs towards targeted drug. Nitrogen mustard drugs are cytotoxic, but usually unselective. It has been reported that nitrophenylacetic acid compounds can be used as triggers for producing bioreductive prodrugs 10, 12, 2829.
Bioreductive, prodrug, tumor hypoxia, clinical trial, oxidoreductase. However, the synthetic process of this bioreductive prodrug is more complex and the antitumor activity of this bioreative prodrug is comparable with ptx. Embedded with a bioreductive delivery and cleavable system in cancer tissues, cucurbitacin bbased prodrugs 1, 2, and 3 were synthesized and evaluated by in vitro and in vivo experiments. Synthesis of novel paclitaxel prodrugs designed for bioreductive activation in hypoxic tumour tissue. The prodrug predrug, proagent term was introduced for the first time by albert as a. In most cases, prodrugs contain a promoiety linker that is removed by enzymatic or chemical reactions, while other prodrugs release their active drugs after molecular modi. Drugs and their modifying effects on the human body ryan d. It can be exploited to produce drug selectivity, offering a reductaserich environment for prodrug activation. Targeting the hypoxic fraction of tumours using hypoxiaactivated. Narcotics hallucinogens depressants stimulants types of drugs. Integrating tumor hypoxic stress in novel and more adaptable strategies for.
Browse pdr s full list of drug information alphabetically by choosing the first letter of the drug you are tying to locate. Synthesis and biological properties of bioreductively targeted. Preferential killing of cancer cells can occur in one of two ways or via of the combination of the two. In this work, several bioreductive prodrugs of cub were designed to reduce toxicity to normal cells while maintaining the cytotoxic effect to cancer cells. We also describe the curre nt knowledge o f how each pro drug class is activated an d detail the c linical. These socalled bioreductive prodrugs are constructed in such a way that metabolic reduction leads to the production of a cytotoxic species which can then damage and kill the malignant cells. Bioreductive prodrugs can be designed for selective activation under low oxygen conditions typical of many solid tumors. Hypoxiaactivated prodrugs haps could target radiationresistant hypoxic cells in tumors.