Novel 1-(2-{3-/4-[(alkoxycarbonyl)amino]phenyl}-2-hydroxyethyl)-4-(2-fluorophenyl)-piperazin-1-ium chlorides (alkoxy = methoxy to butoxy; 8a-h) have been designed and synthesized through multistep reactions as a part of on-going research programme focused on finding new antimycobacterials. Lipophilic properties of these compounds were estimated by RP-HPLC using methanol/water mobile phases with a various volume fraction of the organic modifier. The log kw values, which were extrapolated from intercepts of a linear relationship between the logarithm of a retention factor k (log k) and volume fraction of a mobile phase modifier (ϕM), varied from 2.113 (compound 8e) to 2.930 (compound 8h) and indicated relatively high lipophilicity of these salts. Electronic properties of the molecules 8a-h were investigated by evaluation of their UV/Vis spectra. In a next phase of the research, the compounds 8a-h were in vitro screened against M. tuberculosis CNCTC My 331/88 (identical with H37Rv and ATCC 2794), M. kansasii CNCTC My 235/80 (identical with ATCC 12478), a M. kansasii 6 509/96 clinical isolate, M. avium CNCTC My 330/80 (identical with ATCC 25291) and M. avium intracellulare ATCC 13950, respectively, as well as against M. kansasii CIT11/06, M. avium subsp. paratuberculosis CIT03 and M. avium hominissuis CIT10/08 clinical isolates using isoniazid, ethambutol, ofloxacin, ciprofloxacin or pyrazinamide as reference drugs. The tested compounds 8a-h were found to be the most promising against M. tuberculosis; a MIC = 8 μM was observed for the most effective 1-(2-{4-[(butoxycarbonyl)amino]phen-ylphenyl}-2-hydroxyethyl)-4-(2-fluorophenyl)piperazin-1-ium chloride (8h). In addition, all of them showed low (insignificant) in vitro toxicity against a human monocytic leukemia THP-1 cell line, as observed LD50 values > 30 μM indicated. The structure-antimycobacterial activity relationships of the analyzed 8a-h series are also discussed.

• Keywords
• Mycobacterium tuberculosis H37Rv, N-arylpiperazines, arylaminoethanols, electronic properties, lipophilicity,
• MeSH
• Antitubercular Agents chemical synthesis   chemistry   pharmacology   MeSH
• Hydrophobic and Hydrophilic Interactions MeSH
• Humans MeSH
• Microbial Sensitivity Tests MeSH
• Molecular Structure MeSH
• Mycobacterium tuberculosis drug effects   MeSH
• Cell Line, Tumor MeSH
• Piperazines chemical synthesis   chemistry   pharmacology   MeSH
• Spectrum Analysis MeSH
• Cell Survival drug effects   MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antitubercular Agents MeSH
• Piperazines MeSH

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. intracellulare and three strains of M. avium. 2,3-Dihydro-1-methyl-2-thioxoindole-3-one and 2,3-dihydro-1-butyl-2-thioxoindole-3-one were the most active substances against potentially pathogenic strains, being more active than isoniazide.

• MeSH
• Anti-Bacterial Agents chemistry   pharmacology   MeSH
• Antitubercular Agents pharmacology   MeSH
• Indoles chemistry   pharmacology   MeSH
• Isoniazid pharmacology   MeSH
• Microbial Sensitivity Tests MeSH
• Mycobacterium avium Complex drug effects   MeSH
• Mycobacterium fortuitum drug effects   MeSH
• Mycobacterium kansasii drug effects   MeSH
• Mycobacterium tuberculosis drug effects   MeSH
• Nontuberculous Mycobacteria drug effects   MeSH
• Thiones chemistry   pharmacology   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH
• Names of Substances
• 2,3-dihydro-1-butyl-2-thioxoindole-3-one MeSH Browser
• 2,3-dihydro-1-methyl-2-thioxoindole-3-one MeSH Browser
• Anti-Bacterial Agents MeSH
• Antitubercular Agents MeSH
• Indoles MeSH
• Isoniazid MeSH
• Thiones MeSH

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. Correlation of this action with lipophilicity (log P, 1-octanol-water system) was used for the description of the structure-antimycobacterial activity relationships (QSARs). The activity increased with the increasing lipophilicity of the compounds.

• MeSH
• Anti-Bacterial Agents chemistry   pharmacology   MeSH
• Antitubercular Agents pharmacology   MeSH
• Phenylcarbamates chemistry   pharmacology   MeSH
• Quantitative Structure-Activity Relationship MeSH
• Quaternary Ammonium Compounds chemistry   pharmacology   MeSH
• Microbial Sensitivity Tests MeSH
• Molecular Structure MeSH
• Mycobacterium avium drug effects   MeSH
• Mycobacterium kansasii drug effects   MeSH
• Mycobacterium tuberculosis drug effects   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Antitubercular Agents MeSH
• Phenylcarbamates MeSH
• Quaternary Ammonium Compounds MeSH

A set of 21 1-phenyl-5-benzylsulfanyltetrazoles substituted on the phenyl ring as well as on the benzyl moiety was evaluated for in vitro antimycobacterial activity against Mycobacterium avium and two strains of M. kansasii. We tried to use the Hansch approach, the Free-Wilson approach and their combination for structure-activity correlation but the calculations were statistically insignificant.

• MeSH
• Anti-Bacterial Agents chemistry   pharmacology   MeSH
• Humans MeSH
• Microbial Sensitivity Tests MeSH
• Mycobacterium avium drug effects   pathogenicity   MeSH
• Mycobacterium kansasii drug effects   pathogenicity   MeSH
• In Vitro Techniques MeSH
• Tetrazoles chemistry   pharmacology   MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Tetrazoles MeSH

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. intracellulare and three strains of M. avium. Quinoline-4-carbaldehyde-S-hexyl-isothiohydrazone was found to be more active against potentially pathogenic strains than isoniazide.

• MeSH
• Aldehydes chemistry   pharmacology   MeSH
• Anti-Bacterial Agents pharmacology   MeSH
• Microbial Sensitivity Tests methods   MeSH
• Mycobacterium avium Complex drug effects   MeSH
• Mycobacterium avium drug effects   MeSH
• Mycobacterium fortuitum drug effects   MeSH
• Mycobacterium kansasii drug effects   MeSH
• Mycobacterium tuberculosis drug effects   MeSH
• Nontuberculous Mycobacteria classification   drug effects   MeSH
• Thiosemicarbazones chemistry   pharmacology   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Aldehydes MeSH
• Anti-Bacterial Agents MeSH
• Thiosemicarbazones MeSH

A group of 31 of alkoxy-substituted phenylcarbamic acids with the alkoxy group in ortho, meta or para position, and methyl or ethoxymethyl attached to the ethylene moiety in position 1, including both basic ethyl esters and derivatives branched on ethylene, were evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis, M. kansasii, and M. avium. To describe the structure-antimycobacterial activity relationships (QSARs), an approach based on a combination of the Free-Wilson analysis was used to express the influence of the substituents on the ethylene group as well as the position of the alkoxy groups on the phenyl ring and of the hydrophobicity of alkyls. In vitro antimycobacterial activity becomes higher with increasing hydrophobic properties of the alkoxy groups. The para- and meta-substituted derivatives were more active than the ortho-substituted ones. Substitution of ethylene in position 1 by methyl increased the activity against M. tuberculosis, a similar substitution by ethoxymethyl increased the activity against M. kansasii. The most active compounds were piperidinyl-1-(ethoxymethyl)ethylesters of heptoxyphenylcarbamic acids.

• MeSH
• Antitubercular Agents chemistry   pharmacology   MeSH
• Carbamates chemical synthesis   chemistry   pharmacology   MeSH
• Microbial Sensitivity Tests MeSH
• Mycobacterium avium drug effects   MeSH
• Mycobacterium kansasii drug effects   MeSH
• Mycobacterium tuberculosis drug effects   MeSH
• Structure-Activity Relationship MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antitubercular Agents MeSH
• Carbamates MeSH
• phenylcarbamic acid MeSH Browser