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The synthesis and anti-Candida activity of 1-[(3-aroyloxy-3-phenyl)propyl]-1H-imidazoles 5a-f and 1-[(3-alkyl/aralkyl/phenyl-3-phenyl)propan-3-ol]-1H-imidazoles 5g-j are reported. The influence of the ester formation and different substitutions on the anti-Candida activity of the alcohol 4 was investigated. Among the newly developed bioactive chemical entities, compounds 5b and 5c displayed minimum inhibitory concentrations (MICs) against Candida albicans and Candida pseudotropicales comparable to that of tioconazole and more potent than miconazole.

The essential oils of fresh leaves of Eucalyptus globulus L. (Myrtaceae), and leaves and stems of Smyrnium olusatrum L. (Apiaceae), obtained by hydrodistillation in a Clevenger-type apparatus, were analyzed by GC/MS. Twenty compounds were characterized, representing 98.3% of the essential oil of E. globulus, with 1,8-cineole (48.6%), globulol (10.9%), trans-pinocarveol (10.7%), and α-terpineol (6.6%) as main components, while thirty-three compounds were characterized, representing 94.3% of the essential oil of S. olusatrum, with sabinene (27.1%), curzerene (13.7%), methyl-1-benzyl-2oxocyclooctane carboxylate (12.3%), α-pinene (7.2%), cryptone (7.1%) and β-pinene (5.7%) as the major components. The essential oils of E. globulus and S. olusatrum were tested against a wide range of fungal and bacterial strains. Both oils showed significant antimicrobial activity.

Feeding tritium labeled N-methyl phenylalanine and a number of N-methylated and unmethylated cyclic and acyclic anthranilic-acid-phenylalanine-peptides, the biosynthesis of the benzodiazepine alkaloids cyclopenin and cyclopenol by Penicillium cyclopium wits investigated. The results show that only the two N-methylated cyclic peptides, cyclo-(An-MePhe) and 3,iOdehydro-cyclo-(An-MePhe) were incorporated without degradation and marked depression of the incorporation rate by non-radioactive phenylalanine.The negative results with the acyclic dipeptides, N-methylphenylalanine and cyclo-(An-Phe), some of which should be intermediates in the biosynthesis of cyclo-(An-MePhe), indicate that the formation of the latter proceeds via enzyme bound intermediates as it was found also for more complex cyclic peptide derivatives like gramicidine S. Aside the formation of the peptide bonds, the N-methylation seems to be part of the reaction sequence on this enzyme complex, too.By looking for cyclo-(An-MePhe) and its dehydroderivative in cultures of P. cyclopium, two hitherto unknown benzodiazepine derivatives were isolated. Their structures were elucidated by physico-chemical methods and comparison with synthetic material. The compounds were called cyclopeptine and dehydrocyclopeptine and identified as cyclo-[anthranoyl-(8)-N-methyl phenylalanyl] and 3,10-trans-dehydro-cyclo-[anthanoyl-N-methyl phenylalanyl] respectively. m-Hydroxylated derivatives of both substances, the structure of which would correspond to that of cyclopend were not detectable. The biosyntheses of cyclopeptine and dehydrocyclopeptine from phenylalanine and the coordinated formation of both compounds together with cyclopenin and cyclopenol during the mould's idiophase further prove that they are true intermediates in the synthesis of benzodiazepine alkaloids in P. cycbpium. Cyclopeptine can be reversibly transformed into dehydrocyclopeptine.According to these and former experimental results the biosynthesis of the benzodiazepine and quinoline alkaloids of P. cyclopium secms to proceed in the following manner: The precursor amino acids (S)-phenylalanine and anthranilic acid together with the methylgroup of methionine form an enzyme bound acyclic dipeptide intermediate (presumably an anthranoyl-(8)-N-methyl phenylalanyl thioester) which undergoes cyclization to the benzodiazepin derivatives to release cyclopeptin from the enzyme. Cyclopeptin with NAD as hydrogen acceptor forms dehydrocyclopeptin in the presence of cyclopeptine dehydrogenase. Dehydrocyclopeptine by an epoxydation requiring molecular oxygen is tramformed to cyclopenin, which upon rn-hydroxylation yields cyclopenol. Both, cyclopenin and cyclopenol, in the conidiospores are converted by cyclopenase to the quinoline derivatives, viridicatin and viridicatol.Bei der Untersuchung der Biosynthese der Alka-Verbindungen aus allen Cund N-Atomen von loide Cyclopenin und Cyclopenol bei Penicillium Anthranilsaure und (S)-Phenylalanin sowie aus der cyclopium Westling wurde festgestellt, da13 das Koh-Methylgruppe...

A series of novel spiroimidazolidinone derivatives 6a-d and 8a-x were synthesized and biologically evaluated for their anticonvulsant activity in the maximal electroshock seizure (MES) assay and the subcutaneous pentylenetetrazole (scPTZ) screening test. Compound 8w was the most active derivative in the scPTZ screening test with an ED50 value by about 5- and 83.6-fold lower than those of phenobarbital and ethosuximide as reference drugs, respectively. Most of the tested compounds exhibited moderate to weak activity in the MES screen test, except for 8a which displayed 100% protection at 0.09 mmol/kg. Moreover, all the test compounds did not show any minimal motor impairment in the neurotoxicity test.