Synthesis of Diarylamidines

Diarilamidini su klasa organskih spojeva različite kemijske strukture, čiji se mehanizam djelovanja temelji na nekovalentnim interakcijama u malom utoru DNA. Radi priprave biološki aktivnih spojeva iz klase diarilamidina do danas su provedene brojne sinteze, koje su dovele do razvoja novih sintetskih postupaka kao i priprave novih reagensa i katalizatora. U ovom radu navedene su najčešće primjenjivane sintetske metode priprave diarilamidina.Diarylamidines is a class of compounds of different chemical structure, whose mechanism of action is based on their noncovalent interactions with the minor groove of DNA. The numerous chemical syntheses carried out during the preparation of diarylamidines have led to the development of new synthetic methods and the preparation of new reagents and catalysts. This article summarizes the most used synthetic methods for preparation of diarylamidines

Novel symmetric bis-benzimidazoles: Synthesis, DNA/RNA binding and antitrypanosomal activity.

The novel benzimidazol-2-yl-fur-5-yl-(1,2,3)-triazolyl dimeric series with aliphatic and aromatic central linkers was successfully prepared with the aim of assessing binding affinity to DNA/RNA and antitrypanosomal activity. UV-Visible spectroscopy, thermal denaturation showed interaction of heterocyclic bis-amidines with ctDNA. Circular dichroism studies indicated uniform orientation of heterocyclic bis-amidines along the chiral double helix axis, revealing minor groove binding as the dominant binding mode. The amidino fragment and 1,4-bis(oxymethylene)phenyl spacer were the main determinants of activity against Trypanosoma brucei. The bis-benzimidazole imidazoline 15c, which had antitrypanosomal potency in the submicromolar range and DNA interacting properties, emerged as a candidate for further structural optimization to obtain more effective agents to combat trypanosome infections

Synthesis of Diarylamidines

Diarilamidini su klasa organskih spojeva različite kemijske strukture, čiji se mehanizam djelovanja temelji na nekovalentnim interakcijama u malom utoru DNA. Radi priprave biološki aktivnih spojeva iz klase diarilamidina do danas su provedene brojne sinteze, koje su dovele do razvoja novih sintetskih postupaka kao i priprave novih reagensa i katalizatora. U ovom radu navedene su najčešće primjenjivane sintetske metode priprave diarilamidina.Diarylamidines is a class of compounds of different chemical structure, whose mechanism of action is based on their noncovalent interactions with the minor groove of DNA. The numerous chemical syntheses carried out during the preparation of diarylamidines have led to the development of new synthetic methods and the preparation of new reagents and catalysts. This article summarizes the most used synthetic methods for preparation of diarylamidines

Diarylamidines: Design, Interaction with DNA and Biological Activity Departments

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