Evolution of Nitrogen-Based Alkylating Anticancer Agents

Ingredient-Metal Based Anticancer Agents

2-Sulfonylpyrimidines: Mild alkylating agents with anticancer activity toward p53-compromised cells.

The tumor suppressor p53 has the most frequently mutated gene in human cancers. Many of p53's oncogenic mutants are just destabilized and rapidly aggregate, and are targets for stabilization by drugs. We found certain 2-sulfonylpyrimidines, including one named PK11007, to be mild thiol alkylators with anticancer activity in several cell lines, especially those with mutationally compromised p53....

The Mechanism of Action of Alkylating Agents.

The term “alkylating agent― has been defined and a detailed discussion made of the mechanisms (Sni and Sn@) by which they interact with nucleophilic centers. The various nucleophiles likely to be encountered in vivo are discussed in terms of their relative reactivities toward alkylating agents. With regard to Sn@ reactors it was possible to group them into four sections on the basis of thei...

Inhalation carcinogenesis of various alkylating agents.

A series of earlier studies showed that inhalation exposures of rats to three water-reactive electrophilic compounds produced brisk yields of nasal cancer even when the animals were exposed for only 30 days (6 hr/day X 5 day/wk). In addition, carcinogenic potencies of the compounds appeared to relate to their chemical reactivities as measured by hydrolysis rates. For a further study of this phe...

Mechanisms of Action of Cancer Chemotherapeutic Agents: DNA-Interactive Alkylating Agents and Antitumour Platinum-Based Drugs

The long-term understanding of cancer growth is that it is a net result of uncontrolled multiplication of cells that out paces the rate of natural cell death within the tumour mass. The ultimate aim of the tumour is survival by overcoming the many barriers in its path. The imperative need for continual supply of nutrients to new growth areas, for instance, is met through sustained angiogenesis....