3.8. Enediynes with pH-Based Triggering Devises

3.8. 1. Introduction

Tumor cells have acidic pH. The pH of these cells again becomes low when they are administered hyperglycaemic agents while the normal cells remain unaffected. Thus, greater selectivity against tumor cells is expected with enediynes triggered by acidic pH. This is the most striking phenomenon that led the scientists to design and synthesize tumor specific enediyne warheads. Although there is no apparent advantage if the triggering happens physiological pH (higher that the pH of tumor cell), several designed enediyneprodrugs were activated under mild basic condition. Some of these prodrugs showed excellent IC₅₀ values against a number of cancer cell lines. Many of these showed selectivity against cancer cells.

3.8.2. Approaches for Enediynes with pH-Based Triggering

Various strategies are adapted for pH-based triggering of enediynes which can be classified into the following five categories (Scheme 61). Examples of each category are subsequently described.

Scheme 61. Strategies for designing enediynes with pH-based triggering devices.