Mechanism based, anticancer agents

A recent review [51] focuses mainly on the applications of click reaction in the synthesis of agents with mechanism-based anticancer activity, which are divided into four groups Topoisomerase 11 inhibitors, HDAC inhibitors, protein tyrosine kinase (PTK) inhibitors, and antimicrotubule agents. 

Mechanism-based inactivation of CYP450 (or suicide inhibition) occurs when a non-toxic drug is metabolised by CYP450 to generate a metabolite that can bind irreversibly with the enzyme. The mechanism of inhibition usually involves free-radical alkylation or acylation of the active site and results in destruction of enzyme activity. Examples of drugs that act in this way include the antibiotic chloramphenicol and the anticancer agent cyclophosphamide. 

Anthracycline antibiotics represented by daunomycin and adriamycin are weU known as anticancer agents and their reaction mechanisms with DNA have been extensively studied. However, an approach to understand the mechanism of drug action based on organic synthesis is still open. 

Some of the clinically important drugs that have been identified to be mechanism-based CYP3A4 inhibitors include antibiotics (e g., erythromycin), anticancer drugs (e.g., irinotecan), antidepressants (e g., fluoxetine and paroxetine), anti-FIIV agents (e.g., ritonavir and... 

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