Search

Taking into account that benzimidazole, benzothiazole and benzoxazole nuclei, as a part of nitrogen heterocycles, are highly-privileged building structural motifs in organic and medicinal chemistry, they played unavoidable role in the rational drug design. Among their versatile pharmacological features, the most important ones are antimicrobial, antitumor, antiviral, anti- inflammanory, antihistaminic, antioxidant, etc. On the other hand, amidines are known as important pharmacophore functional groups usually placed at the termini of the biologically active molecules. They are a structural parts of the numerous biologically active compounds and many important medical and biochemical agents. Amidine groups, usually in cationic form, could significantly contribute to the molecule/possible biological target complex stability. Herein we present the synthesis, structural characterization and biological evaluation of amidino substituted benzimidazole and benzothiazole derivatives substituted with 2- naphthyl ring. All targeted compounds have been synthesized according to the conventional methods of organic synthesis. They have been evaluated on the several human cancer cell lines for their antiproliferative activity in vitro. Additionally, all synthesized compounds have been tested against several Gram negative and Gram positive bacterial strains in vitro.

Due to the great biological importance of benzimidazole and benzothiazole derived derivatives, nowadays there is still an increasing interest in medicinal and pharmaceutical chemistry for using this unavoidable structural motifs in the rational design of novel drugs. Suchlike derivatives display a broad spectrum of different biological features such as anticancer, antiviral, antioxidant, antibacterial, antifungal, antihistaminic, anti-inflammatory, etc. Amidines are structural parts of numerous biologically active compounds like many important medical and biochemical agents. By introduction of amidino functional groups at the termini of the molecule, the biological activity could be significantly improved because of interaction with an electronegatively charged biological molecule such as DNA. Herein we present the synthesis and biological evaluation of novel amidino substituted benzimidazole and benzothiazole derivatives substituted with 2-hydroxyphehyl ring in the position 2. All compounds were tested for their antiproliferative activity on several human cancer cells as well as for antibacterial activity in vitro.

Among all known nitrogen heterocycles, benzimidazole and benzothiazole moieties have been recognized as important and well-known constituents of biologically important molecules in medicinal and pharmaceutical chemistry [1, 2]. Due to their wide range of biological activities, these heterocycles are still unavoidable structural motifs in the rational design of novel drugs. Newly designed and synthesized cyano, amidino and acrylonitrile 2, 5-disubstituted furane derivatives with either benzimidazole/benzothiazole nuclei have been evaluated for antitumor and antimicrobial activity, as well as for their interaction with ct-DNA. Compounds 5, 6, 8, 9 and 15 showed high potential antitumor activity on three human lung cancer cell lines and high activity against S. cerevisiae as a eukaryotic model organism. DNA study showed that all compounds dominantly bind inside the minor groove of AT-rich DNA.

Background: As incidence of infections caused by bacteria resistant to one or more antibiotic classes increases, there is a constant need for development of new, more effective and safe antimicrobial drugs. Macrolones are a novel class of antibacterial macrolide compounds, characterized by a quinolone moiety attached via linker by an ester bond to 4’’ position of macrolide scaffold. Methods: Antibacterial activity of macrolones against key respiratory pathogens was determined and their pharmacodynamics assessed using time- kill methodology. Macromolecular synthesis and TnT assay were used to test mechanism of action. In vitro resistance development potential was determined by measuring spontaneous mutation rates and by passage studies in sub-inhibitory concentrations of compounds. In vivo efficacy was tested in murine pneumonia model. Results: Macrolone spectrum of activity comprises key bacterial respiratory pathogens with in vitro profiles superior to those of marketed macrolide antibiotics and ketolide telithromycin, including macrolide resistant S. pneumoniae, S. pyogenes and S. aureus strains (overall more than 250 clinical isolates tested). Representative macrolone compound exhibits MIC90 values against MLSb S. pneumoniae and H. influenzae comparable to telithromycin, while superior against iMLSb and cMLSb strains of S.pyogenes (MIC90

Inhibitori dihidrofolat reduktaze (DHFR), enzima koji katalizira sintezu 5, 6, 7, 8- tetrahidrofolata, već se niz godina koriste u terapijske svrhe kao antibiotici i antimetaboliti. Premda strukturno pripadaju različitim klasama, većina DHFR inhibitora sadrži 2, 4-diamino supstituirani pirimidinski prsten. S ciljem skretanja pozornosti na derivate pirimido-pirimidina kao novu klasu inhibitora bakterijske DHFR (bDHFR), ispitana su 42 spoja te klase te je njihovo inhibitorno djelovanje uspoređeno s 18, strukturno sličnih, spojeva pteridinske klase, pripadnici koje su prethodno opisani kao inhibitori DHFR. Za odabrane spojeve obje klase ispitano je protubakterijsko djelovanje (određivanjem minimalne inhibitorne koncentracije), inhibicija proliferacije eukariotskih stanica (određivanjem citotoksičnog učinka), inhibicija bakterijskog i ljudskog DHFR enzima (određivanjem IC50 vrijednosti) te je učinjeno molekulsko uklapanje, dok je najpotetniji spoj dodatno okarakteriziran te uspoređen s trimetoprimom, poznatim inhibitorom bDHFR. Nekoliko spojeva iz pirimido-pirimidinske klase pokazalo se potetnim (IC50≤0, 05 μM) i selektivnim inhibitorima bDHFR te je utvrđeno da njihova inhibitorna svojstva ovise o uskoj strukturnoj slobodi i fleksibilnosti koja se temelji na točno određenim strukturnim motivima koji im omogućavaju uklapanje u aktivno središte bDHFR na relativno specifičan način. Prikazani rezultati predstavljaju temelj za dizajn i razvoj novih malih molekula, inhibitora DHFR, sa zanimljivim i potencijalno selektivnim protubakterijskim svojstvima.

Analitička evaluacija sa statističkom obradom i ocjenom novog tipa stroja za biokemijske pretrage u humanim uzorcima. Provedena je istovremeno u 2 klinička laboratorija a zajednički rezultati evaluacije 20 analita pokazali su dobre radne osobine sustava, usporedive rezultate s postojećim sustavima i izvrsne KV% ispod dopuštenih bioloških i analitičkih varijabilnosti za svaki pojedini analit.