Diarylamidines: Design, Interaction with DNA and Biological Activity Departments

Abstract

Diarilamidini čine skupinu biološki aktivnih spojeva koji se više od pola stoljeća upotrebljavaju za tretman parazitskih bolesti. Iako mehanizam njihovog biološkog djelovanja još nije potpuno razjašnjen, utvrđeno je kako je biološka aktivnost posljedica vezanja u mali utor DNA. Zbog toga su spojevi iz ove klase, prvotno razvijani radi pronalaska lijekova protiv parazitskih bolesti, s vremenom prepoznati kao lijekovi potencijalno široke primjene (protiv npr. HIV-oportunističkih infekcija ili tumora) koja se temelji na interakciji s DNA - primarnim genskim materijalom. Pojava rezistencije i nekih neželjenih pratećih posljedica potakla je istraživanja i razvoj novih učinkovitijih lijekova kao i određivanje mehanizma njihovog djelovanja na molekulskom nivou. U ovom radu dan je pregled istraživanja utjecaja strukture pojedinih diarilamidina na afinitet i selektivnost pri vezanju u mali utor DNA i na njihovu biološku aktivnost.Diarylamidines are a group of biologically active compounds that are more than half a century used for treatment of parasitic diseases. Although the biological mechanism of action has not yet been fully explained it was found that the biological activity of compounds of this class is based on their binding in a small groove of DNA. Therefore, the compounds of this class, originally developed for the purpose of finding parasitic drugs, over time are recognized as potential drugs with broad application (e. g. anti-HIV opportunistic infections or tumours) based on their interaction with DNA - the primary genetic material. The occurrence of resistance and some associated adverse consequences prompted the research and development of new effective drugs and finding their mechanism of action at the molecular level. In the first part of this work, basic concepts are given accompanied by selected examples of this class of compounds

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