Design, Synthesis, and Biological Evaluation of Isothiosemicarbazones with Antimycobacterial Activity.

A series of benzaldehyde and salicylaldehyde-S-benzylisothiosemicarbazones was synthesized and tested against 12 different strains of mycobacteria, Gram-positive and Gram-negative bacteria, and the significant selectivity toward mycobacteria was proved. Twenty-eight derivatives were evaluated for the inhibition of isocitrate lyase, which is a key enzyme of the glyoxylate cycle necessary for latent tuberculosis infection, and their iron-chelating properties were investigated. Two derivatives, 5-bromosalicylaldehyde-S-(4-fluorobenzyl)-isothiosemicarbazone and salicylaldehyde-S-(4-bromobenzyl)-isothiosemicarbazone, influenced the isocitrate lyase activity and caused a better inhibition at 10 μmol/L than 3-nitropropionic acid, a standard inhibitor.

Prediction of retention characteristics of heterocyclic compounds.

The CORAL software ( http://www.insilico.eu/coral ) was used to build up quantitative structure-property relationships (QSPRs) for the retention characteristics of 93 derivatives of three groups of heterocyclic compounds: 2-phenyl-1,3-benzoxazoles, 4-benzylsulfanylpyridines, and benzoxazines.

Structure-activity relationships of N-benzylsalicylamides for inhibition of photosynthetic electron transport.

Inhibition of photosynthetic electron transport (PET) in spinach chloroplasts by sixty-one ring-substituted N-benzylsalicylamides was investigated. The inhibitory potency of the compounds expressed by IC50 value varied from 2.0 to 425.

Synthesis and biological activity of quaternary ammonium salt-type agents containing cholesterol and terpenes.

New quaternary ammonium salt-type compounds with lipophilic cholesterol and terpene moieties were synthesized. The compounds showed promising antibacterial and antimycobacterial activities. Those compounds containing the cholesterol moiety showed significant activity against Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium.

[Where does the development of new antituberculotics go? Part 2 - in vitro evaluation].

The present paper is a continuation of a publication of 2012 (Čes. a slov. Farm.

SMILES-based quantitative structure-property relationships for half-wave potential of N-benzylsalicylthioamides.

Optimal descriptors calculated with Simplified Molecular Input Line Entry System (SMILES) notation have been used in quantitative structure-property relationships (QSPR) of half-wave potential of N-benzylsalicylthioamides. The QSPR developed is one-variable model based on the optimal descriptors calculated with the Monte Carlo method. The approach has been checked up with three random splits into the training and test sets.

Phenyl salicylates - a new group of potential antituberculotics.

Antimycobacterial activity of phenyl salicylates (salols) was studied in connection with antituberculotic activity of salicylic derivatives. Phenyl salicylates are esters. Our attention was previously oriented on amides.

[Where does the development of new antituberculotics aim at?].

Several research teams in the Czech and Slovak Republics are oriented on the development of new antitubeculotics. The present article is based mainly on the information from the Chemical Abstracts from the year 2011 and the beginning of the year 2012. It is a selection from almost three thousand reports aiming to help our scientists.

[Derivatives of phenylcarbamic acid as potential antituberculotics].

Basic esters of phenylcarbamic acid were studied by the teams of Prof. Cizmárik and Prof. Waisser as potential antituberculotics.

New S-benzylisothiosemicarbazones with antimycobacterial activity.

Benzaldehyde- and salicylaldehyde-S-benzylisothiosemicarbazones show a moderate to high in vitro activity against Mycobacterium tuberculosis, Mycobacterium avium and two strains of Mycobacterium kansasii. Benzaldehyde-S-4-bromobenzylisothiosemicarbazone and salicylaldehyde-S-4-chlorobenzylisothiosemicarbazone have the most promising antimycobacterial properties.

Highly active antimycobacterial derivatives of benzoxazine.

New 3-(4-alkylphenyl)-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones and 3-(4-alkylphenyl)-2H-1,3-benzoxazine-2,4(3H)-dithiones were synthesized. The compounds were tested for in vitro antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium avium and two strains of Mycobacterium kansasii. The antimycobacterial activity increased with the replacement of the carbonyl group by the thiocarbonyl group in the starting 3-(4-alkylphenyl)-2H-1,3-benzoxazine-2,4(3H)-diones.

Antibacterial activity of N-benzylsalicylthioamides.

The in-vitro biological activity of N-benzylsalicylthioamides against 8 bacterial strains was determined by broth microdilution method; results were compared with those obtained with neomycin, penicillin G, ciprofloxacin and penicillin V. The compounds showed moderate to high activity against G(+) bacteria; especially compounds 4, 6, 13, 16-21 and 24 exhibited comparable or higher activity than reference drugs. The antibacterial activity was analyzed by quantitative structure-activity relationship (QSAR).

N-Benzylsalicylthioamides as novel compounds with promising antimycotic activity.

The in vitro biological activity of N-benzylsalicylthioamides was evaluated against eight fungal strains by the broth microdilution method and the results were compared with those obtained with fluconazole. The compounds exhibited an in vitro antifungal activity against the fluconazole-susceptible as well as the fluconazole-resistant fungal strains. The biological activity was analyzed by quantitative structure-activity relationship (QSAR).

A note to the biological activity of benzoxazine derivatives containing the thioxo group.

New 3-benzyl-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones and 3-benzyl-2H-1,3-benzoxazine-2,4(3H)-dithiones were synthesized. The compounds were tested for in vitro antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium kansasii and Mycobacterium avium. The replacement of the carbonyl group by the thiocarbonyl group increased the antimycobacterial activity.

N-benzylsalicylthioamides: highly active potential antituberculotics.

A gseries of 29 new derivatives of N-benzylsalicylthioamides was synthesized and the compounds were tested for in-vitro antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium kansasii, and Mycobacterium avium. The activity was analyzed by quantitative structure-activity relationship (QSAR). Activity increased with increasing lipophilicity and electron donating effect of the substituents in the acyl moiety and decreased with the electrophilic superdelocalizability of the molecules.

Highly active potential antituberculotics: 3-(4-alkylphenyl)-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones and 3-(4-alkylphenyl)-2H-1,3-benzoxazine-2,4(3H)-dihiones substituted in ring-B by halogen.

A series of 6-chloro-3-(4-alkylphenyl)-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones, 7-chloro-3-(4-alkylphenyl)-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones, 6-bromo-3-(4-alkylphenyl)-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones, 6,8-dibromo-3-(4-alkylphenyl)-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones, 6-chloro-3-(4-alkylphenyl)-2H-1,3-benzoxazine-2,4(3H)-dithiones, 7-chloro-3-(4-alkylphenyl)-2H-1,3-benzoxazine-2,4(3H)-dithiones, 6-bromo-3-(4-alkylphenyl)-2H-1,3-benzoxazine-2,4(3H)-dithiones and 6,8-dibromo-3-(4-alkylphenyl)-2H-1,3-benzoxazine-2,4(3H)-dithiones was synthesized. The compounds exhibited in-vitro activity against Mycobacterium tuberculosis, M. kansasii (two strains), and M.

Preparation and in vitro evaluation of benzylsulfanyl benzoxazole derivatives as potential antituberculosis agents.

A set of 2-benzylsulfanyl derivatives of benzoxazole was synthesized and evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis, non-tuberculous mycobacteria and multidrug-resistant M. tuberculosis. The activities were expressed as the minimum inhibitory concentration (MIC) in mmol/L.

QSAR analysis of salicylamide isosteres with the use of quantum chemical molecular descriptors.

Quantitative relationships between the molecular structure and the biological activity of 49 isosteric salicylamide derivatives as potential antituberculotics with a new mechanism of action against three Mycobacterial strains were investigated. The molecular structures were represented by quantum chemical B3LYP/6-31G( *) based molecular descriptors. A resulting set of 220 molecular descriptors, including especially electronic properties, was statistically analyzed using multiple linear regression, resulting in acceptable and robust QSAR models.

The oriented development of antituberculotics (Part II): halogenated 3-(4-alkylphenyl)-1,3-benzoxazine-2,4-(3H)-diones.

Based on our previous studies, 21 new halogenated 3-(4-alkylphenyl)-1,3-benzoxazine-2,4-(3H)-diones were synthesized by the reaction of salicylanilides and methyl-chloroformate. All compounds were screened in vitro against three different strains of mycobacterium, and Free-Wilson method was used to establish structure-activity relationships. 6-Bromo-3-(4-butylphenyl)-1,3-benzoxazine-2,4-(3H)-dione 3b proved to be the most active compound of the series.

Hybrid molecules of estrone: new compounds with potential antibacterial, antifungal, and antiproliferative activities.

New hybrid molecules of estrone were synthesized as compounds indicating promising biological activity (antibacterial, antimycobacterial, antifungal, and antiproliferative). The prepared molecules contained various heterocyclic units (pyridine, benzylsulfanyl derivatives of pyridine or derivatives of tetrazole) linked to estrone by n-heptyl bridges. The compounds with charge on molecule (the hybrid pyridinium or benzylsulfanylpyridinium salts) exhibited significant biological activity (antibacterial, antimycobacterial, antifungal, and antiproliferative).

QSPR modeling of the half-wave potentials of benzoxazines by optimal descriptors calculated with the SMILES.

Optimal descriptors calculated with Simplified Molecular Input Line Entry System (SMILES) notation have been used in quantitative structure-property relationships (QSPR) modeling electrochemical half-wave potential of benzoxazine derivatives by one-variable correlations.

The oriented development of antituberculotics: salicylanilides.

On the basis of our previous results 22 salicylanilides were synthesized. The compounds were tested for in vitro antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium kansasii, and Mycobacterium avium. The Free-Wilson method was used to evaluate structure-antimycobacterial activity relationships.

New antimycobacterial 2,3-dihydro-1-alkylindole-2-thiones.

A series of 2,3-dihydroindole-2-thiones was evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis, M. kansasii, M. fortuitum, two strains of M.

QSAR study of antimycobacterial activity of quaternary ammonium salts of piperidinylethyl esters of alkoxysubstituted phenylcarbamic acids.

A series of 17 halogenides of quaternary ammonium salts of the alkylpiperidinylethyl esters of 2-pentoxy (and 2-heptoxy) substituted phenylcarbamic acids were evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis, M. kansasii, and M. avium.

New antimycobacterial S-alkylisothiosemicarbazones.

In connection with a systematic study of antimycobacterial agents against potentially pathogenic strains the series of 12 S-alkylisothiosemicarbazones was evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis, M. kansasii, M. fortuitum, two strains of M.