Polymeric Conjugates of Selected Aminoquinoline Derivatives as Potential Drug Adjuvants in Cancer Chemotherapy

Abstract

In the chemotherapy of cancerous diseases, the clinical co-administration of an active anti-tumor drug with other compounds acting as potentiating agents or adjuvants has demonstrated considerable merits in comparison with single-drug administration. Selected members of the 4- and 8-aminoquinoline-based class of antimalarials, such as chloroquine and hydroxychloroquine, have been identified as providers of such adjuvant effects in combination with certain standard antitumor drugs, although no significant clinical experiences have as yet been reported. The here described project aims at the synthesis of water-soluble macromolecular carriers to which selected aminoquinolines are bioreversibly conjugated together with cytotoxic drug species exemplified by a diaminoplatinum(II) complex and by the organoiron compound, ferrocene, the latter being a relative newcomer to the family of organometallic antineoplastic agents. As most medicinal agents differ from each other by their pharmacokinetic path and, therefore, experience different rates and degree of body distribution and organ accumulation, the simultaneous availability of two or more mutually potentiating drug species can best be achieved if a common transport vehicle, such as a multifunctional carrier polymer of the type synthesized in this study, is utilized for this purpose. The conjugates and co-conjugates, isolated by conventional methods as water-soluble solids, are compositionally characterized by NMR-spectroscopic and microanalytical techniques.