1, 3-Dipolar Cycloaddition (Part I): Synthesis of 1, 2, 3-Triazole Derivatives in Nucleoside Chemistry

Bakrom katalizirana Huisgenova 1, 3-dipolarna cikloadicija azida i terminalnih alkina kojom regioselektivno nastaju 1, 4-disupstituirani 1, 2, 3-triazoli često je primjenjivana metoda sintetske organske kemije. Zahvaljujući jednostavnim reakcijskim uvjetima, zauzela je značajno mjesto i u području nukleozidne kemije jer omogućuje dobivanje velikog broja potencijalno biološki aktivnih spojeva s nizom zanimljivih dodatnih svojstava induciranih uvođenjem 1, 2, 3-triazolnog strukturnog motiva u molekulu.Copper catalysed Huisgen 1,3-dipolar cycloaddition of azides and alkynes which leads to 1,4-disubstituted-1,2,3-triazoles is a frequently used method in synthetic organic chemistry. Due to the simple reaction conditions, it has occupied an important place in the field of nucleoside chemistry since it enables preparation of a large number of potentially biologically active compounds with a number of interesting additional properties induced by the presence of 1,2,3-triazole structural motif in the molecule

Effects of quinoline-arylamidine hybrids on LPS-induced inflammation in RAW 264.7 cells

Background and purpose: Inflammation is a common pathogenesis in infection, injury, cancer, and many chronic diseases. Macrophages are among the main cells involved in generation of inflammation. The aim of the present study was to investigate the effects of molecular hybrids with 7-chloroquinoline and arylamidine moieties joined through flexible a 2-aminoethanol linker, on the in vitro inflammatory responses to lipopolysaccharides (LPS) induced inflammation in the RAW 264.7&nbsp;cells. Materials and methods: To determine effects of seven quinoline-arylamidine hybrids on the growth of the murine macrophage-like (RAW 264.7) cells MTT assay was used. Inflammatory reactions in the RAW264.7 cells were induced using E. coli lipopolysaccharides (LPS). Levels of nitric oxide (NO) and malondialdehyde (MDA) were determined by spectrophotometry methods. Intracellular production of reactive oxygen species (ROS) was measured by flow cytometry. Antioxidant capacity of tested compounds was tested by 2,2\u27-azino-bis(3-ethybenzthiazoline-6-sulfonic acid (ABTS) radical cation method. Results: Tested hybrid compounds differentially influenced proliferation of non-stimulated and LPS-stimulated RAW 264.7 cells. The hybrid compounds have not presented ABTS radical-scavenger activity. In the LPS-stimulated RAW 264.7 cells 10 μM compounds slightly decreased production of NO and ROS and significantly modulated LPS-induced lipid peroxidation. Conclusions: Molecular hybrids with 7-chloroquinoline and arylamidine moieties joined through flexible 2-aminoethanol linker markedly decreased accumulation of lipid peroxidation products in the LPS-stimulated RAW 264.7 cells. Further studies are necessary to determine their mechanism of anti-inflammatory action in more details. &nbsp; Keywords: Hybrid molecules, 7-Chloroquinoline, Aromatic amidine, Anti-inflammatory activity in vitro</p

Synthesis and In vitro Activity of N-sulfonylamidine-derived Pyrimidine Analogues

Two novel series of N-sulfonylamidino pyrimidine derivatives were synthesized via Cu-catalyzed three-component reaction of propargylated nucleobases with different benzenesulfonyl azides and amines. In this way 4-acetamido, 4-methyl and 4-carboxybenzenesulfonyl amidine products 15–26 in the uracil series and 4-acetamidobenzenesulfonyl amidine derivatives 27–29 in the cytosine series were prepared in 34−69 % yields. Attempts to prepare N-sulfonylamidino cytosine derivatives in reaction with 4-methylbenzenesulfonyl azide were unsuccessful. The cytosine derivatives 32 and 33 were prepared from the N-sulfonylamidino uracil derivatives via the C4 triazole intermediates. The prepared N-sulfonylamidino pyrimidine derivatives 1–28 were tested for the antiproliferative activity on a panel of seven tumor cell lines of different histological origin (HeLa, Caco-2, NCI-H358, Raji, HuT78, K562, Jurkat) and on normal MDCK I cells. Most of the synthesized compounds showed antiproliferative activity on the tested cell lines

Raznolikost i prevalencija Salmonella spp. u galebovima ulovljenih na odlagalištu otpada, Zagreb, Hrvatska

Gulls are a group of seabirds distributed worldwide that are an important reservoir of Salmonella spp. Salmonellosis is the second most commonly reported gastrointestinal infection in humans, and understanding the role wild birds have in spreading Salmonella can help to improve the health of humans and domestic animals. The mobility and migration capacity of gulls makes them an interesting group for research given their potential role in spreading pathogens. This paper presents the diversity and prevalence of Salmonella spp. in different gull species caught at a landfill in Zagreb in the winter months over a nine-year period from 2014-2022. In total, 1083 cloacal swabs were sampled from six gull species: Black-headed Gull (Larus ridibundus), Yellow-legged Gull (L. michahellis), Caspian Gull (L. cachinnans), Common Gull (L. canus), Lesser Black-back Gull (L. fuscus) and Herring Gull (L. argentatus). The prevalence of Salmonella was 5.82%, and 16 Salmonella serotypes were identified; S. Typhimurium had the highest prevalence (47.62%) followed by S. Enteritidis (12.69%) and S. Infantis (9.52%). To date, 82 Salmonella serotypes have been isolated in research on gulls in Europe, with S. Typhimurium as the most common, followed by S. Agona and S. Enteritidis. In this study, we found three serotypes not previously reported in gulls, S. Yalding, S. Reading and one with the antigenic formula O:17; H:z10; H:e,n,x,z15 (IIIb).Galebovi su skupina morskih ptica raširenih diljem svijeta koje su važan rezervoar Salmonella spp. Salmoneloza je druga najčešće prijavljena gastrointestinalna infekcija u ljudi i razumijevanje uloge koju divlje ptice imaju u širenju Salmonella spp. može pomoći u poboljšanju zdravlja ljudi i domaćih životinja. Mobilnost i migracijska sposobnost čini galebove vrlo zanimljivom skupinom za istraživanje zbog njihove potencijalne uloge u širenju patogena. Kroz ovaj rad prikazujemo raznolikost i prevalenciju Salmonella spp. kod nekoliko vrsta galebova ulovljenih na odlagalištu otpada tijekom zime u Zagrebu kroz devetogodišnje razdoblje, 2014.-2022. Ukupno je uzorkovano 1083 obrisaka kloake od šest vrsta galebova: riječni galeb (Larus ridibundus), galeb klaukavac (L. michahellis), pontski galeb (L. cachinnans), burni galeb (L. canus), tamnoleđi galeb (L. fuscus) i srebrnasti galeb (L. argentatus). Ukupna prevalencija Salmonella spp. je 5,82 % sa 16 identificiranih serotipova. S. Typhimurium ima najveću zastupljenost (47,62 %), zatim S. Enteritidis (12,69 %) i S. Infantis (9,52 %). Prema istraživanjima prisutnosti serotipova Salmonella spp. u galebova u Europi izolirana su njih 82, a najčešće dokazani je S. Typhimurium, zatim S. Agona i S. Enteritidis. Tijekom ovog istraživanja identificirana su tri serotipa koja ranije nisu izdvojena iz galebova S. Yalding i S. Reading te jedan iz podvrste S. enterica subsp. diarizonae (IIIb_O:17; H:z10; H:e,n,x,z15)

Synthesis, anti-bacterial and anti-protozoal activities of amidinobenzimidazole derivatives and their interactions with DNA and RNA.

Amidinobenzimidazole derivatives connected to 1-aryl-substituted 1,2,3-triazole through phenoxymethylene linkers 7a-7e, 8a-8e, and 9a-9e were designed and synthesised with the aim of evaluating their anti-bacterial and anti-trypanosomal activities and DNA/RNA binding affinity. Results from anti-bacterial evaluations of antibiotic-resistant pathogenic bacteria revealed that both o-chlorophenyl-1,2,3-triazole and N-isopropylamidine moieties in 8c led to strong inhibitory activity against resistant Gram-positive bacteria, particularly the MRSA strain. Furthermore, the non-substituted amidine and phenyl ring in 7a induced a marked anti-bacterial effect, with potency against ESBL-producing Gram-negative E. coli better than those of the antibiotics ceftazidime and ciprofloxacin. UV-Vis and CD spectroscopy, as well as thermal denaturation assays, indicated that compounds 7a and 8c showed also binding affinities towards ctDNA. Anti-trypanosomal evaluations showed that the p-methoxyphenyl-1,2,3-triazole moiety in 7b and 9b enhanced inhibitory activity against T. brucei, with 8b being more potent than nifurtimox, and having minimal toxicity towards mammalian cells

Pojavnost bakterije Listeria monocytogenes i drugih vrsta roda Listeria u galebova koji se hrane na zagrebačkom odlagalištu otpada, Hrvatska

Gulls, as migratory wild birds are known to spread different pathogens over long distances. The aim of this study was to access the prevalence of different Listeria species in a gull population feeding at a landfill in Zagreb. In total, 390 gulls of three species were sampled: Yellow-legged Gull, Larus michahellis; Black-headed Gull, L. ridibundus and Common Gull, L. canus. The most prevalent species was Listeria innocua (14.4%), while L. monocytogenes was found in 11.3% of tested samples. Other species were present in a smaller percentage; L. welshimeri (1.3%), L. ivanovii (0.5%) and L. seeligeri (0.3%). Serotyping of L. monocytogenes isolates was performed using molecular and conventional methods, and most isolates belonged to the 1/2a and 1/2b serotypes. To the best of our knowledge, this is the first report of the presence of L. monocytogenes and other Listeria spp. in wild birds in Croatia.Za galebove je kao divlje ptice selice poznato da mogu na velike udaljenosti širiti različite patogene. Cilj je ovog istraživanja bio odrediti prevalenciju različitih vrsta roda Listeria u populaciji galebova koji se hrane na Zagrebačkom odlagalištu otpada. Sveukupno je pretraženo 390 galebova triju vrsta: galeb klaukavac - Larus michahellis; riječni galeb - L. ridibundus i burni galeb - L. canus. Najzastupljenija vrsta bila je L. innocua (14,4 %), dok je L. monocytogenes dokazana u 11,3 % ispitanih uzoraka. Prisutnost ostalih vrsta zastupljena je u manjem postotku i to L. welshimeri (1,3 %), L. ivanovii (0,5 %) i L. seeligeri (0,3 %). Serotipizacija izolata L. monocytogenes provedena je molekularnim i konvencionalnim metodama, a većina izolata pripadala je serotipovima 1/2a i 1/2b. Prema našem saznanju, ova studija donosi prve rezultate istraživanja prisutnosti L. monocytogenes i drugih vrsta roda Listeria u divljih ptica u Hrvatskoj

Synthesis of Novel Aliphatic N-sulfonylamidino Thymine Derivatives by Cu(I)-catalyzed Three-component Coupling Reaction

A series of new aliphatic N-sulfonylamidino thymine derivatives containing nucleobase, N-sulfonyl and amidine pharmacophores in the structure were synthesized by Cu(I)-catalyzed threecomponent coupling of 1-propargyl thymine, benzenesulfonyl azides and amines or ammonium salts. Preliminary in vitro antitumor screening (human cervix adenocarcinoma -HeLa and leukemia cells - Jurkat) revealed promising activities of N,N-diethyl- (2) and N-4-cyanobenzyl- (6) derivatives of 4-acetamidobenzenesulfonyl amidine. (doi: 10.5562/cca2198

Design, synthesis, antitrypanosomal activity, DNA/RNA binding and in vitro ADME profiling of novel imidazoline-substituted 2-arylbenzimidazoles

Novel imidazoline benzimidazole derivatives containing diversely substituted phenoxy moieties were synthesized with the aim of evaluating their antitrypanosomal activity, DNA/RNA binding affinity and in vitro ADME properties. The presence of the diethylaminoethyl subunit in 18a-18c led to enhanced antitrypanosomal potency, particularly for 18a and 18c, which contain unsubstituted and methoxy-substituted phenoxy moieties. They were found to be > 2-fold more potent against African trypanosomes than nifurtimox. Fluorescence and CD spectroscopy, thermal denaturation assays and computational analysis indicated a preference of 18a-18c toward AT-rich DNA and their minor groove binding mode. Replacement of the amidine group with less basic and ionisable nitrogen-containing moieties failed to improve membrane permeability of the investigated compounds. Due to structural diversification, the compounds displayed a range of physico-chemical features resulting in variable in vitro ADME properties, leaving space for further optimization of the biological profiles