Abstract 482: Multiple chemical action cancer therapeutics

Abstract

Abstract Radiation-produced quasi-free electrons (i.e., low energy electrons in solutions) causes DNA damage. However, there are no evidence that radiation-produced partially solvated electrons (i.e., presolvated or, prehydrated electrons) and fully solvated electrons (i.e., aqueous or solvated electrons) cause strand breaks. However, recent work on azidoDNA-model systems show that radiation-produced electrons can be converted to highly damaging aminyl radicals (RNH•) which do have the potential to cause strand breaks. Experimental studies in our labs (both in vitro and in vivo) have shown that 2-deoxy-D-glucose (2-DG), a glucose mimic and glycolytic inhibitor, enhances radiation-induced damage selectively in tumor cells while protecting normal cells and against infection. Thereby suggesting that 2-DG can be used as a differential radiomodifier to improve the efficacy of cancer radiotherapy. Based on these experimental results and data mining models, we show that the azido derivative of 2DG; 2-Azido-2-deoxy-D-glucose (2-AZ-2-DG) has unique azido chemistries. The neutral aminyl radical produced from 2-AZ-2-DG under reductive environment undergoes facile conformational change from the stable chair form to the reactive boat form. Subsequently, this aminyl radical causes H-atom abstraction from C5 of the sugar moiety via proton-coupled electron transfer process. Further, a promise as multivalent drug to augment multipronged cellular damage including site-specific DNA radiation damage and also counter infections persisting in several cancer cases. Our long range goals are to harness these unique chemistries in gold based nanotools for X-PDT (X-ray induced photodynamic therapy). Citation Format: Rao Papineni, Amithava Adhikary. Multiple chemical action cancer therapeutics [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 482.