Rhodanine-based biologically active molecules: synthesis,characterization, and biological evaluation

To investigate the antimicrobial properties of the rhodanine (2-thioxo-4-thiazolidinone) structure, several 2-[(5Z)-5-benzylidene-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-N-phenylacetamide derivatives were synthesized by use of an efficient procedure. Variation of the functional group on the 5-benzylidine ring of rhodanine led to compounds containing a 2-thioxo-4-thiazolidinone group attached to N-phenyl acetamide. The chemical structures of the compounds were confirmed by IR, ¹H NMR, and ¹³C NMR spectroscopy, ESI mass spectrometry, and elemental analysis. The antibacterial and antifungal activity of the compounds were tested, at seven concentrations, against Gram-positive bacterial strains (Pseudomonas aeruginosa ATCC 27853 and Escherichia coli ATCC 25922), Gram-negative bacterial strains (Staphylococcus aureus ATCC 25923 and Bacillus subtilis ATCC 11774), and fungal strains (Candida albicans ATCC 66027 and Aspergillus niger ATCC 6275), by use of the Kirby Bauer disk-diffusion technique and the serial broth dilution technique. The results obtained were compared with those for reference drugs. Relationships between structure and their antimicrobial activity are discussed.     

Metallation of diazines. V. Synthesis of analogues of biologically active molecules

2-Chloro-4-methoxypyrimidine was lithiated by lithium 2,2,6,6-tetramethylpiperidide. The resulting lithio derivative was reacted with carbonyl derivatives and iodine. Synthesis of analogues of biologically active molecules is reported.     

Developing novel organocatalyzed aldol reactions for the enantioselective synthesis of biologically active molecules

Aldol reaction is one of the most important methods for the formation of carbon-carbon bonds. Because of its significance and usefulness, asymmetric versions of this reaction have been realized with different approaches in the past. Over the last decade, the area of organocatalysis has made significant progresses. As one of most studied reactions in organocatalyses, organocatalyzed aldol reaction has emerged as a powerful tool for the synthesis of a large number of useful products in optically enriched forms. In this review, we summarize our efforts on the development of novel organocatalyzed aldol reactions for the enantioselective synthesis of biological active molecules. Literatures closely related to our studies are also covered.     

A new dendrimer scaffold for preparing dimers or tetramers of biologically active molecules

Synthesis of a new scaffold derived from iminodipropionic acid for the preparation of peptide dimers and tetramers is described.     

Synthesis,spectral characterisation and thermal studies of zirconyl complexes of biologically active molecules

Zirconyl complexes of hippuric acid (C₉H₉NO₃, hipH) and monophenylbutazone (4-butyl-1-phenyl-3,5-pyrazolidinedione, MPB) were prepared using ZrOCl₂ · 8H₂O and ZrO(NO₃)₃ · xH₂O and characterized by elemental analysis, molar conductance measurement and IR, UV–Vis and NMR spectral methods. Thermal decomposition behaviour was studied by thermogravimetry. The second harmonic generation (SHG) conversion efficiency of hippuric acid complexes was also studied.     

Application of photoelectron spectroscopy to biologically active molecules and their constituent parts IV. Methylnitroimidazoles

Photoelectron (PE) spectra of imidazole ( 1), 1 -methylimidazole ( 2 ), 2-methylimidazole ( 3 ), 4(5)-nitroimidazole ( 4 ), 2-methyl-4(5)nitroimidazole ( 5 ), 1,2-dimethyl-5-nitroimidazole ( 6 ), 1-ethyl-2-methyl-5-nitroimidazole ( 7 ), 1-bromoethyl-2-methyl-5-nitroimidazole ( 8 ) and 1-hydroxyethyl-2-methyl-5-nitroimidazole ( 9 ) have been recorded using Hel excitation. The electronic structure of the potent antitrichomonal agent 9 is discussed in comparison with compounds 1–8 allowing for the study of the influence of substituents on the imidazole ring.     

Synthesis of biologically active pyridazinoquinoxalines

The 2‐(1‐methylhydrazino)quinoxaline 4‐oxides 9a,b were converted into the pyridazino[3,4‐b]‐quinoxalines 10a,b,15a,b,22 and 1,2‐diazepino[3,4‐b]quinoxalines 29a‐c , which were further transformed into the 3‐substituted 1‐methylpyridazino[3,4‐b]quinoxalin‐4(1H)‐ones 5–8 .     

Acid catalyzed isomerization of bicyclic alkenes: a facile betweenanene synthesis

Isomerization of $\text{cis}$-bicyclo[10.8.0]eicos-1(12)-ene ($\text{1a}$) and $\text{cis}$-bicyclo[10.10.0]docos-1(12)-ene ($\text{1b}$) to [10.8]- and [10.10]betweenanene ($\text{2a}$ and $\text{2b}$) has been effected by sulfuric acid. In both cases, the betweenanene isomers were found to predominate at equilibrium (70/30 $\text{2a}$/$\text{1a}$ and 95/5> $\text{2b}$/$\text{1b}$).     

Symmetry of nonrigid molecules and isomerization processes

Starting from the concept of a totally flexible molecule, rigidity is introduced by restricting progressively the allowed permutations. Each nonrigid isomer is then characterized by its Longuet-Higgins group ? of allowed permutation inversions. For a given ? all nonrigidity types correspond to all possible choices of the symmetry subgroup ? of the skeleton. The structure of ? also allows a characterization of the isomerization processes studied in chemical kinetics. In both situations, isomerization mechanisms may be associated with generators and are, in the simplest situations, represented by Cayley graphs.     

Theoretical density functional theory studies on interactions of small biologically active molecules with isolated heme group

We present ab-initio density functional theory studies on the interactions of small biologically active molecules, namely NO, CO, O(2), H(2)O, and NO(2) (-) with the full-size heme group. Our results show that the small molecule-iron bond is the strongest in carbonyl and the weakest in nitrite system. Trans influence induced by NO binding to the five-coordinate heme complex is shown. Nitric oxide in the resulting complex might be described as NO(-). The differences among the small ligands of XO type (CO, NO, O(2)), and their distant chemical behavior from H(2)O and NO(2) (-) ligands in binding to the Fe(II) ion, are shown. Moreover, the role of the heme ring as a reservoir of electrons in the studied complexes is invoked. The analysis of the parameters defining the iron-histidine bond indicates that this bond is longer and weaker in nitrosyl and carbonyl complexes than in the other systems. Our findings support the proposed mechanism of soluble guanylate cyclase (sGC) activation and suggest that the first step of sGC activation by CO may be the same as during the activation by NO. Obtained results are then compared with the data concerning smaller model of the heme, the porphyrin complexes, available in the literature.     

Mass spectrometry of biologically active substances

The mass spectra of 2- and 4-iminobarbituric acid derivatives were studied in relation to the mass spectra of their oxygen analogs. It is shown that the pathways of fragmentation of the investigated compounds depend on the type of substituent attached to the C₅ atom, the position of the imino and oxo groups in the ring, and the specific mass-spectral properties. The fragmentation was studied by means of low-voltage mass spectrometry and deuterium labeling.See [1] for communication I.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 813–817, June, 1978.     

Syntheses of biologically active sialosylglycerol derivatives

New sialosylglycerol derivatives were synthesized and found to inhibit the phospholipase A2 and C activities.     

Electrochemical studies of biologically active indolizines

The electrochemical behavior of indolizine ethers, esters, tosylates, sulfonates and other indolizine and azaindolizine derivatives has been investigated by cyclic voltammetry and preparative electrolysis. The cyclic voltammetric data show that the E° values, taken as the midpoints between the anodic and cathodic peak potentials, are sensitive to the identities of the substituents at C-1, C-2 and C-7 positions. The E° values have been correlated with the Hammett substituent parameters. As expected, low E° values are seen for electron donating substituents and higher E° values are seen for electron withdrawing substituents. The cyclic voltammograms of indolizine derivatives with an oxygen atom connected to the C-1 position exhibit a one-electron reversible oxidation and a further, less well-defined, one-electron irreversible oxidation at higher E° values. The cyclic voltammograms of indolizines with hydrogen atom or thienyl substituents connected to the C-1 position exhibit only a one-electron irreversible oxidation. Electrochemical bulk oxidations of indolizines with an oxygen atom at the C-1 position afforded oxoindolizinium salts in decent yields, whereas indolizines with a hydrogen atom at C-1 afforded 1,1′ dimers of indolizines as products in good yields. Bulk oxidation of 1-(α-hydroxybenzyl)-2,3-diphenylindolizine-7-carbonitrile afforded an unexpected ketone product in which the carbonyl group of the indolizine is connected at C-8 instead of at the C-1 position of the starting material. The findings described herein support our hypothesis that certain indolizine derivatives may inhibit lipid peroxidation by an electron transfer mechanism.     

Silyl modification of biologically active compounds

A series of derivatives of (1,2,3,4-tetrahydro-1-quinolyl)-, (1,2,3,4-tetrahydro-2-isoquinolyl)-, and (1,2,3,4-tetrahydrosila-2-isoquinolyl)acetic acid, which are structural analogs of glycine, were synthesized. The psychotropic activity and the acute toxicity of the compounds were studied.For Communication 3, see [6].Latvian Institute of Organic Synthesis, Riga. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 270–274, February, 1997.     

Synthesis of new biologically active O-hydrometalatranes

Russian Journal of General Chemistry -