Synthesis of Substituted Derivatives of closo-Decaborate Anion with a Peptide Bond: The Way towards Designing Biologically Active Boron-Containing Compounds

This article presents studies on the targeted search for new derivatives of azoles, such as benzthiazole, 3,5-dimethylpyrazole, 1,3,4-oxadiazole-2-thione, 1,3,4-thiadiazole. The possibility of combining in one molecule of the azole ring with other cyclic compounds: the alkaloid cytisine, morpholine, furan and some arenes has been studied. To obtain new compounds, the reactions of bromination, acylation, and interaction with isothiocyanates were studied. Optimal synthesis conditions were studied for all reactions. It was found that the reaction of 4-bromo-3,5-dimethylpyrazole with isothiocyanates, in contrast to the previously written derivatives of anilines, takes a longer time and requires heating the reaction mixture. The combination of a pirasol fragment with halide substituents often results in an enhanced therapeutic effect. The synthesized 2-bromine-N-(6-rodanbenzo[d]thiazole-2-yl)acetamide, due to the alkylbromide group, is an important synth in the synthesis of new benzthiazole derivatives. Its derivatives combine in one molecule the rest of rhodanbenzthiazole with alkaloid cytisine and biogenic amine morpholine and are potentially biologically active compounds, since the molecule structure contains several pharmacophoric fragments: benzthiazole and alkaloid (amine) heterocycles, rhodane and urea groups. The mechanism of formation of 1,3,4-oxadiazole-2-tyons from hydrazides under action on them by carbon disulfide was studied and assumed. It was shown that dithiocarbamates in acidic medium decompose with the release of hydrogen sulfide and the formation of highly reactive isothiocyanate group. Then, intra-molecular cyclization occurs, with the formation of end products - 1,3,4-oxadiazole-2-thions. The structures of the synthesized compounds were studied by 1H and 13C NMR spectroscopy. All synthesized substances are potentially biologically active compounds, since they contain several pharmacophore fragments in their structure.

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Synthesis of 5'-O-phosphonomethyl derivatives of biologically active nucleosides

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc1990s125 ◽

1990 ◽

Vol 55 (s1) ◽

pp. 125-128

Author(s):

J. Brokeš ◽

A. Holý

Keyword(s):

Biologically Active ◽

Derivatives Of

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Quantum-Chemical Search for Keto Tautomers of Azulenols in Vacuo and Aqueous Solution

Symmetry ◽

10.3390/sym13030497 ◽

2021 ◽

Vol 13 (3) ◽

pp. 497

Author(s):

Ewa D. Raczyńska

Keyword(s):

Aqueous Solution ◽

Quantum Chemical ◽

Biologically Active ◽

Deprotonation Reaction ◽

Chemical Studies ◽

Quantum Chemical Studies ◽

Scanty Information ◽

Derivatives Of ◽

Common Anion ◽

Tautomeric Mixture

Keto-enol prototropic conversions for carbonyl compounds and phenols have been extensively studied, and many interesting review articles and even books appeared in the last 50 years. Quite a different situation takes place for derivatives of biologically active azulene, for which only scanty information on this phenomenon can be found in the literature. In this work, quantum-chemical studies have been undertaken for symmetrically and unsymmetrically substituted azulenols (constitutional isomers of naphthols). Stabilities of two enol (OH) rotamers and all possible keto (CH) tautomers have been analyzed in the gas phase {DFT(B3LYP)/6-311+G(d,p)} and also in aqueous solution {PCM(water)//DFT(B3LYP)/6-311+G(d,p)}. Contrary to naphthols, for which the keto forms can be neglected, at least one keto isomer (C1H, C2H, and/or C3H) contributes significantly to the tautomeric mixture of each azulenol to a higher degree in vacuo (non-polar environment) than in water (polar amphoteric solvent). The highest amounts of the CH forms have been found for 2- and 5-hydroxyazulenes, and the smallest ones for 1- and 6-hydroxy derivatives. The keto tautomer(s), together with the enol rotamers, can also participate in deprotonation reaction leading to a common anion and influence its acid-base properties. The strongest acidity in vacuo exhibits 6-hydroxyazulene, and the weakest one displays 1-hydroxyazulene, but all azulenols are stronger acids than phenol and naphthols. Bond length alternation in all DFT-optimized structures has been measured using the harmonic oscillator model of electron delocalization (HOMED) index. Generally, the HOMED values decrease for the keto tautomers, particularly for the ring containing the labile proton. Even for the keto tautomers possessing energetic parameters close to those of the enol isomers, the HOMED indices are low. However, some kind of parallelism exists for the keto forms between their relative energies and HOMEDs estimated for the entire molecules.

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Synthesis of biologically active derivatives of cyclopenteno[d]-selenazole and their thioanalogs

Pharmaceutical Chemistry Journal ◽

10.1007/bf00759752 ◽

1982 ◽

Vol 16 (6) ◽

pp. 460-463

Author(s):

A. A. Tsurkan ◽

Z. F. Gromova ◽

�. A. Rudzit ◽

G. N. Neshchadit ◽

D. A. Kulikova

Keyword(s):

Biologically Active ◽

Derivatives Of ◽

Biologically Active Derivatives

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Chemical modification and Physicochemical properties of new derivatives 5-(thiophen-3-ilmethyl)-4-R1-1,2,4-triazole-3-thiol

Research Journal of Pharmacy and Technology ◽

10.52711/0974-360x.2021.00803 ◽

2021 ◽

pp. 4621-4629

Author(s):

O.A. Bihdan ◽

V.V. Parchenko

Keyword(s):

Physicochemical Properties ◽

High Reactivity ◽

Biologically Active Compounds ◽

Biologically Active ◽

Active Compounds ◽

Triazole Derivatives ◽

Pharmaceutical Ingredients ◽

Current Trends ◽

Wide Range ◽

Derivatives Of

Current trends in the search for new biologically active compounds among synthetic molecules have arguably proved a priority in studies of the heterocyclic 1,2,4-triazole system. For many years, 1,2,4-triazole derivatives remain the object of close attention of scientists of various scientific fields. The unique properties of 1,2,4-triazole derivatives include high reactivity, which allows different modification of this system, practical absence of toxicity of these derivatives and the presence of a wide range of biological, pharmacological properties, which in the complex provides the prerequisites for the creation of new biologically active compounds, and in the future, active pharmaceutical ingredients (AFI). The aim of our work is to investigate some transformations in a number of derivatives of 5-(thiophen-3-ylmethyl) -4-R1-1,2,4-triazole-3-thiol, to study the physicochemical properties of the new synthesized compounds. A well-known fact remains the successful attempt of many scientists involved in the study of the heterocyclic 1,2,4-triazole system to synthesize potential biologically active compounds. The process of creating new molecules is very painstaking and requires considerable effort. The chemical approaches for the synthesis of the starting compounds required for further transformations are well known and described. Therefore, we used the corresponding N-R1-2 as intermediates for the synthesis of new 5-(thiophen-3-ylmethyl) -4-R1-1,2,4-triazole-3-thiols appropriate ones were used N-R1-2-(2-(thiophen-3-yl) acetyl) hydrazinocarbothioamide.

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TYRAMINE, HISTAMINE, AND TRYPTAMINE CONTENT OF CHEESE

Journal of Milk and Food Technology ◽

10.4315/0022-2747-37.7.377 ◽

1974 ◽

Vol 37 (7) ◽

pp. 377-381 ◽

Cited By ~ 42

Author(s):

M. N. Voigt ◽

R. R. Eitenmiller ◽

P. E. Koehler ◽

M. K. Hamdy

Keyword(s):

Cheddar Cheese ◽

The United States ◽

Quantitative Information ◽

Biologically Active ◽

Blue Cheese ◽

Physiological Importance ◽

Fluorescence Measurements ◽

Soft Cheese ◽

Layer Chromatography ◽

Derivatives Of

Because of the increasing knowledge of the physiological importance of biologically active amines in man and the importance of the presence of these amines in cheese, this study was done to obtain quantitative information for tyramine, tryptamine, and histamine in cheese available in the United States. The tyramine, histamine, and tryptamine contents of 156 samples of cheese purchased at retail stores were quantitated by thin-layer chromatography and fluorescence measurements of NBD-chloride derivatives of the amines. Tyramine was found in 81 of 85 Cheddar cheese samples examined. Extra-sharp, sharp, and medium Cheddar cheese samples contained average tyramine values of 0.27, 0.21, and 0.24 mg/g, respectively. Average tyramine contents were lower in mild and processed Cheddar (0.09 and 0.11 mg/g, respectively). The highest Cheddar cheese tyramine content was 0.7 mg/g. Tyramine was consistently found in all cheeses except in unripened soft cheese (Cottage). Histamine concentrations varied from nondetectable amounts to 2.6 mg/g in a Sap-Sago cheese sample. Twenty-four Cheddar cheese samples contained histamine with the highest amount being 1.3 mg/g. A domestic Blue cheese contained 2.3 mg/g. Tryptamine was uniformly low or completely absent in the Cheddar cheese samples. The highest tryptamine concentration (1.1 mg/g) was detected in a Blue cheese.

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Conformation–activity relationships and the mechanism of action of penicillin

Canadian Journal of Chemistry ◽

10.1139/v88-424 ◽

1988 ◽

Vol 66 (11) ◽

pp. 2733-2750 ◽

Cited By ~ 13

Author(s):

Saul Wolfe ◽

Kiyull Yang ◽

Maged Khalil

Keyword(s):

Conformational Analysis ◽

Carbonyl Group ◽

Active Site ◽

Global Minimum ◽

Peptide Bond ◽

Biologically Active ◽

Penicillin G ◽

Side Chain ◽

Geometrical Parameters ◽

Carboxyl Group

Using the MMPEN parameters of Allinger's MMP2(85) force field, a conformational analysis has been performed on four biologically active penicillins; D-ampicillin, L-α-phenoxyethylpenicillin, penicillin G, and penicillin V, and on five biologically inactive or much less active penicillins: L-ampicillin, D-α-phenoxyethylpenicillin, N-methylpenicillin G, 6α-methylpenicillin G, and bisnorpenicillin G. Antibacterial activity is found to be associated with the existence of a global minimum having a compact structure, whose convex face is accessible to a penicillin binding protein (PBP), with the C3-carboxyl group and the side-chain N-H exposed on this face. Using the MMPEP parameters of MMP2(85), a conformational analysis has been performed on phenylacetyl-D-Ala-D-Ala-O−, a peptide model of the normal substrate of a PBP. Labischinski's global minimum has been reproduced, along with structures that correspond to Tipper and Strominger's proposal that the N4—C7 bond of a penicillin corresponds to the Ala–Ala peptide bond, and to Hasan's proposal that the N4—C5 bond of penicillin corresponds to the peptide bond. For both models, conformations of the peptide related to the pseudoaxial and pseudoequatorial conformations of the thiazolidine ring of penicillin G have been examined. It is concluded that penicillin is not a structural analog of the global minimum of the peptide; however, comparisons based on unbound conformations of PBP substrates are unable to determine which model is more appropriate, or which conformation of penicillin G is the biologically significant one. Using the ECEPP/MMPEP strategy, a model of the active site of a PBP has been obtained, following a search of 200,000 structures of the peptide Ac-NH-Val-Gly-Ser-Val-Thr-Lys-NH-Me. This peptide contains the sequence at the active site of a PBP of Streptomyces R61, for which it is also known that the C3-carboxyl group of penicillin binds to the ε-amino group of lysine, and the β-lactam reacts chemically with the serine OH. The lysine and serine side chains and the C-terminal carbonyl group are found to occupy the concave face of the active site model.A strategy for the docking of penicillins or peptides to this model, with full minimization of the conformational energies of the complexes, has been devised. All active penicillins bind through strong hydrogen bonds to the C3-carboxyl group and the side-chain N-H, and with a four-centered relationship between the O-H of serine and the (O)C-N of the β-lactam ring. The geometrical parameters of this relationship are reminiscent of those found in the gas phase transition state of neutral hydration of a carbonyl group. When the energies of formation and geometries of the pseudoaxial and pseudoequatorial penicillin G complexes are examined, there is now a clear preference for the binding of the pseudoaxial conformation, which is the global minimum of the uncomplexed penicillin in this case. A similar examination of the peptide complexes reveals that only the conformation of the peptide that corresponds to Tipper and Strominger's model, and is based on the pseudoaxial conformation of penicillin G, can form a complex with a geometry and energy comparable to those of a biologically active penicillin.

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