Reaktionen mit N-(1- Benzotriazolylcarbonyl)-aminosauren.III Synthese von Aminosaure-estern

N-(l-Benzotriazolylcarbonyl)-aminosauren· (Ia-f) reagieren mit Alkoholen unter Abspaltung von Benzotriazol und Kohlendioxid zu den entsprechenden Aminosaure-Estern. (Ila-i). Die Reaktion verlauft bei Raumtemperatur und wird durch Zugabe von Triethylamin beschleunigt

Antimikrobna aktivnost N-ftaloil-aminokiselinskih hidroksamata

Antibacterial and antifungal activity of N-phthaloylamino acid hydroxamates 1-3 /C6H4(CO)2N-x-CONHOH, x = amino acid residues of glycine, ß-alanine and D-phenylglycine/ was examined against 44 strains of Gram-positive and Gram-negative bacteria, and 10 species of yeasts. The level of antimicrobial effects was established using the in vitro agar assay and the standard broth dilution susceptibility test. N-phthaloyl-D-phenylglycine-hydroxamic acid (3), the substance with the highest lipophilicity (log P), showed the best antibacterial activity, especially against Gram-negative bacteria. Minimum inhibitory concentration of 3 was 0.008 mg mL-1 in the activity against Yersinia enterocolitica O3, confirmed by a large inhibition zone (30 mm) by the diffusion test. Hydroxamates inhibit growth by chelation of PDF enzyme metal in both Gram-positive and Gram-negative bacteria, and LpxC enzyme in Gram-negative enzyme. Phthalimides apear to contribute to inhibition by destabilizing m-RNA. Antifungal activity of substances 1-3 is not very expressed.Ispitano je djelovanje N-ftaloil-aminokiselinskih hidroksamata 1–3 opće formule C6H4(CO)2N-X-CONHOH (X = aminokiselinski ostatak glicina, -alanina ili D-fenilglicina) na 44 soja Gram-pozitivnih i Gram-negativnih bakterija i 10 vrsta kvasaca. Antibakterijski i antifungalni učinak testiran je postupkom difuzije na hranjivom agaru i standardnom metodom dilucije. Najbolja inhibicija rasta, osobito izražena prema Gram-negativnim bakterijama, utvrđena je za N-ftaloil-D-fenilglicin hidroksamsku kiselinu (3) s najvećom lipofilnošću. Za soj Yersinia enterocolitica O3 minimalna inhibitorna koncentracija (0,008 mg mL–1) potvrđena je inhibicijskom zonom od 30 mm pomoću difuzijskog testa. Hidroksamati inhibiraju rast keliranjem metala PDF enzima kod Gram-pozitivnih i Gram-negativnih bakterija, te LpxC enzima kod Gram-negativnih bakterija. Ftalimido struktura pridonosi inhibiciji, pretpostavlja se, destabilizacijom m-RNA. Antifungalna aktivnost spojeva 1–3 nije osobito izražena

3-(Phthalimidoalkyl)-substituted Pyrazolin-5-ones

The syntheses of the 4-ethoxycarbonyl-5-hydroxy-1-phenyl- 3-(a-phthalimidoethyl)pyrazole (2b), and its 0-methyl derivative 3b, as well as N-methyl derivative 4a, are described. The structure of the obtained compounds are discussed on the basis of their infrared, mass and 1H nuclear magnetic resonance spectra

N-ftaloil-glicin-hidroksamska kiselina kao kelator željeza u serumu štakora

The aim of this study was to investigate the activity of N-phthaloyl-glycine-hydroxamic acid (Phth-Gly-HA) as a new iron chelator in vivo to be used in iron overload diseases. After intraperitoneal application of Phth-Gly-HA to male rats (1 mg kg1 body mass) once a day for seven days, iron serum level decreased by 21%, whereas the iron value dropped by 32% in female rats (1.5 mg kg1 body mass). The results indicate that the tested substance has the ability to bind serum iron by complexation. Besides transferrin iron release, mobilization of ferritin iron is also possibleU cilju pronalaženja novog efikasnog kelatora koji bi mogao poslužiti u liječenju bolesti izazvanih viškom željeza, u ovom je radu ispitano djelovanje N-ftaloil-glicin-hidroksamske kiseline (Phth-Gly-HA) in vivo. Istraživan je utjecaj kelatora na razinu željeza u serumu štakora nakon intraperitonealne primjene vodene otopine Phth-Gly-HA (0,1 mg mL1) jednom dnevno tijekom 7 dana. Kontrolne su životinje primale fiziološku otopinu. Kod mužjaka injektiranje test supstancije (1 mg kg1) uzrokovalo je pad serumskog željeza za 21%. Kod ženki je nakon tretmana (1,5 mg kg1) izmjereno sniženje razine željeza za 35%. Rezultati pokazuju da ispitivana supstanca ima sposobnost kompleksiranja serumskog željeza, pretežno transferinskog, ali da postoji mogućnost mobilizacije željeza i iz feritinskih zaliha

Antimicrobial activity of N-phthaloylamino acid hydroxamates

Ispitano je djelovanje N-ftaloil-aminokiselinskih hidroksamata 1–3 opće formule C6H4(CO)2N-X-CONHOH (X = aminokiselinski ostatak glicina, -alanina ili D-fenilglicina) na 44 soja Gram-pozitivnih i Gram-negativnih bakterija i 10 vrsta kvasaca. Antibakterijski i antifungalni učinak testiran je postupkom difuzije na hranjivom agaru i standardnom metodom dilucije. Najbolja inhibicija rasta, osobito izražena prema Gram-negativnim bakterijama, utvrđena je za N-ftaloil-D-fenilglicin hidroksamsku kiselinu (3) s najvećom lipofilnošću. Za soj Yersinia enterocolitica O3 minimalna inhibitorna koncentracija (0,008 mg mL–1) potvrđena je inhibicijskom zonom od 30 mm pomoću difuzijskog testa. Hidroksamati inhibiraju rast keliranjem metala PDF enzima kod Gram-pozitivnih i Gram-negativnih bakterija, te LpxC enzima kod Gram-negativnih bakterija. Ftalimido struktura pridonosi inhibiciji, pretpostavlja se, destabilizacijom m-RNA. Antifungalna aktivnost spojeva 1–3 nije osobito izražena.Antibacterial and antifungal activity of N-phthaloylamino acid hydroxamates 1-3 /C6H4(CO)2N-x-CONHOH, x = amino acid residues of glycine, ß-alanine and D-phenylglycine/ was examined against 44 strains of Gram-positive and Gram-negative bacteria, and 10 species of yeasts. The level of antimicrobial effects was established using the in vitro agar assay and the standard broth dilution susceptibility test. N-phthaloyl-D-phenylglycine-hydroxamic acid (3), the substance with the highest lipophilicity (log P), showed the best antibacterial activity, especially against Gram-negative bacteria. Minimum inhibitory concentration of 3 was 0.008 mg mL-1 in the activity against Yersinia enterocolitica O3, confirmed by a large inhibition zone (30 mm) by the diffusion test. Hydroxamates inhibit growth by chelation of PDF enzyme metal in both Gram-positive and Gram-negative bacteria, and LpxC enzyme in Gram-negative enzyme. Phthalimides apear to contribute to inhibition by destabilizing m-RNA. Antifungal activity of substances 1-3 is not very expressed

3-(Phthalimidoalkyl)-substituted Pyrazolin-5-ones

The syntheses of the 4-ethoxycarbonyl-5-hydroxy-1-phenyl- 3-(a-phthalimidoethyl)pyrazole (2b), and its 0-methyl derivative 3b, as well as N-methyl derivative 4a, are described. The structure of the obtained compounds are discussed on the basis of their infrared, mass and 1H nuclear magnetic resonance spectra

Synthesis of some pyridoxine and pyridoxal halophosphonates

A new series of pyridoxine and pyridoxal chloro and fluorophosphonates have been synthesized. Partially protected pyridoxine 1, 2 or pyridoxal 4 reacted with methyl phosphonic dichloride in the presence of triethylamine at -10 °C. Thus, the following chlorophosphonate derivatives were obtained: 3,4'-0-isopropylidenepyridoxine-5'-0- methylchlorophosphonate (5), 4',5'-0-isobutylidenepyridoxine-3-0- methylchlorophosphonate (6), and monoethylacetalpyridoxal-3-0- methylchlorophosphonate (7). Similarly, from adequate starting compounds 1,3 and unprotected pyridoxal (PL) in the reaction with methyl phosphonic difluoride and triethylamine, near O"C, the corresponding 3-0 or 5'-0-methylfluorophosphonateswere obtained; 3,4'-0 isopropylidenepyridoxine-5'-0-methylfluorophosphonate(8), 4-metoxymethylpyridoxine- 5'-0-methylfluorophosphonate (9) and pyridoxal- 5'-0-methylfluorophosphonate (10)

NMR spectroscopy of 2-hydroxy-1-naphthylidene Schiff bases with chloro and hydroxy substituted aniline moiety

Schiff bases, products of the reaction of primary amines and carbonyl compounds, are involved in many metabolic processes. Hence, physicochemical studies of Schiff bases as model substances can contribute to a better understanding of biological systems. In this work, the oneand two-dimensional homo- and heteronuclear 1H and 13C NMR spectra of 2-hydroxy-1-naphthylidene Schiff bases with differently chloro- and hydroxyl- substituted aniline moiety were studied. The spectra were analyzed on the basis of chemical shifts, substituent effects, spinspin couplings as well as connectivities. It was established that the investigated Schiff bases exist as NH tautomers in DMSO-d6 solution with NH group orientated in cis position relative to the carbonyl of naphthylidene moiety. The positions of substituents on aniline ring were found to be in agreement with intra- and intermolecular hydrogen bond formation. Influence of substituents on planar or nonplanar conformation of compounds is discussed as well

A QSAR study of 3-(phthalimido alkyl)-pyrazolin-5-ones

A group of 17 new 3-(phthalimidoalkyl)-pyrazolin-5-ones were tested for their mitodepressive activity upon the growth of Lepidium sativum L. seeds (Cresson). All of them have shown mitodepressive effect on the growth of the plant. Four topological indices (the Wiener index, the valence-connectivity index, the Balaban index and the information-theoretic index) were used in QSAR studies (inhibition of plant growth in % and cytostatic activity in ED50) on these compounds. We obtained QSAR models that can predict cytostatic activity on the HeLa cells (in ED50) with considerable accuracy

NMR Spectroscopy of 2-Hydroxy-1-naphthylidene Schiff Bases with Chloro and Hydroxy Substituted Aniline Moiety

Schiff bases, products of the reaction of primary amines and carbonyl compounds, are involved in many metabolic processes. Hence, physicochemical studies of Schiff bases as model substances can contribute to a better understanding of biological systems. In this work, the oneand two-dimensional homo- and heteronuclear 1H and 13C NMR spectra of 2-hydroxy-1-naphthylidene Schiff bases with differently chloro- and hydroxyl- substituted aniline moiety were studied. The spectra were analyzed on the basis of chemical shifts, substituent effects, spinspin couplings as well as connectivities. It was established that the investigated Schiff bases exist as NH tautomers in DMSO-d6 solution with NH group orientated in cis position relative to the carbonyl of naphthylidene moiety. The positions of substituents on aniline ring were found to be in agreement with intra- and intermolecular hydrogen bond formation. Influence of substituents on planar or nonplanar conformation of compounds is discussed as well