Synthesis of Porphyrins Derived From the Amidation of Protoporphyrin IX for Use as Potential Chemotherapeutic Agents

Abstract

A series of pure porphyrins (3)-(11) derived from amidation of the carboxylic acid groups of protoporphyrin IX was synthesized in high yield by using 1,11-carbonyldiimidazole as the coupling reagent. Preliminary biological evaluation of these porphyrins revealed that (3) and (10) localize in tumour tissue in concentrations 20 times greater than the surrounding normal tissue. Porphyrins (3)-(5) were found to localize in mitochondria, and this is proposed to account for their greater photosensitivity effectiveness when compared with hematoporphyrin derivative. The extent of binding of the basic porphyrins (3) and (4) to DNA was ascertained by absorbance titrations with DNA, and binding constants were found to be (1.0-1.5) × 10⁶ dm³ mol^-1 with six base pairs occluded for both compounds.