SYNTHESIS AND DNA AFFINITY OF 1-DIALKYLAMINO-3- INDOLO [2,3-b] QUINOXALINE-6-YLPROPAN-2-OLS

Abstract

DNA intercalators demonstrated a broad spectrum of terapeutic activities, such as anticancerogenic, antimicrobic and antiviral as well as ciototoxic, mutagenic and embriotoxic. One of the main marks of DNA-drug interaction is the strength of interaction, which depends on the way of interaction (simple adsorption, minor groove binding or intercalation). It is important to understand that the most potent binder has a great chance to demonstrate high cytotoxic effect and were is no correlation between antiviral activity and association constant (lg Ka) – we only assume the desire range. On the over hand, continual investigation of DNA intercalators (such as fluorenones, acridines, naphthalimides and indoloquinoxalines) as a potential antiviral drugs demonstrated significaly high antiviral and interferonogenic activity and low toxicity of such compounds. On the last stage of our researches we had admit extremely high therapeutic potential of some 6-((dialkylamino)ethyl)indolo[2,3-b]quinoxalines. Due to determine the mode action of indoloquinoxaline intercalators and to expand the number and variety of compounds for the following QSAR calculation we decided to obtain a set of 6-(2-(hydroxy)-3(dialkylamino) propyl)indoloquinoxalines. Claimed compounds were obtained in two-steps synthesis out of unsubstituted indolo[2,3-b]quinoxaline. On the first step we obtained intermediate 6-(oxiranylmethyl)-6H-indolo[2,3-b]quinoxaline by treatment the start compound with epichlorohydrine in basic media. Next condensation of intermediate with dialkylamines lead to target compounds with average yields. DNA binding properties were tested by spectrofluorimetric titration of complex DNA-ethydium bromide with our compounds and presented as lgKa. Comparation of lgKa of target compound with their des-hydroxy analogues shows us a slight decline of DNA binding properties of target compounds, which we connect with steric factors.

Keywords

• індоло[2,3‑b]хіноксалін
• афінітет до ДНК
• органічний синтез