Response of the bioluminescent bioreporter Pseudomonas fluorescens HK44 to analogs of naphthalene and salicylic acid.

Pseudomonasfluorescens HK44 is a lux-based bioluminescent bioreporter capable of selective luminescence in the presence of naphthalene and/or salicylic acid intermediate of its metabolism. We attempted to induce bioluminescence (BL) in this strain with 72 compounds, viz. substituted naphthalenes, naphthalene-like compounds (e.g., quinoline), substituted salicylic acids, salicylic acid-like compounds (e.g., 2-anthranilic acid), oligocyclic aromates, and intermediates of naphthalene metabolism to better discriminate response specificity. From them, 42 induced BL significantly lower as compared to naphthalene, three (viz. isoquinoline, o-cresol, and salicylamide) induced BL significantly greater than naphthalene, and 27 yielded no bioluminescent response whatsoever. Strain HK44 is therefore not prone to extensive false-positive signaling and can serve as a fairly specific indicator organism for naphthalene bioavailability. At elevated concentrations, 41 compounds inhibited BL. Thus, the inclusion of constitutive bioreporter controls as indicators of sample toxicity is vital to successful biosensing application.

Amphotericin B, its lipid formulations and conjugates with polymers.

The minireview is focused on novel findings concerning mechanism of action, lipid formulations, polymer conjugates, and structural modifications of amphotericin B.

Biological activity of 2-hydroxythiobenzanilides and related compounds.

Thiobenzanilides substituted in thioacyl moiety with one or more hydroxy groups are interesting for their biological effects depending on the substitution pattern. New findings in mechanisms of action of 2-hydroxybenzanilides insert 2-hydroxybenzanilides and their analogues, e.g. substituted thiobenzanilides, among interesting compounds in the development of new potential antimicrobial drugs. The present review paper with 32 references links up with our previous communications which reviewed biological activity of 2-hydroxybenzanilides and related compounds, and includes the research of mono-, di-, and trihydroxythiobenzanilides carried out in the last period.

In vitro antifungal activity of 3-phenyl-2H-benzoxazine-2,4(3H)-diones.

A series of 81 3-phenyl-2H-benzoxazine-2,4(3H)-diones with substitution at C(6) on the benzoxazine ring and on the phenyl moiety was synthesized; the compounds were evaluated for antifungal activity against five strains of potentially pathogenic fungi (Absidia corymbifera, Aspergillus fumigatus, Candida albicans, Microsporum gypseum and Trichophyton mentagrophytes). Structure-activity relationships against T. mentagrophytes and M. gypseum were determined using the Free-Wilson method, which was further combined with the approach of Hansch. In vitro antifungal activity becomes higher with increasing electron-accepting ability of the substituents on the phenyl ring, and with increasing lipophilicity.

Influence of the replacement of the oxo function with the thioxo group on the antimycobacterial activity of 3-aryl-6,8-dichloro-2H-1,3-benzoxazine-2,4(3H)-diones and 3-arylquinazoline-2,4(1H,3H)-diones.

Series of 3-phenyl-6,8-dichloro-2H-1,3-benzoxazine-2,4(3H)-dithiones, 3-arylquinazoline-2,4(1H,3H)-diones and 3-arylquinazoline-2,4(1H,3H)-dithiones were synthesized, and the antimycobacterial activities of the derivatives evaluated in vitro. The compounds were active against Mycobacterium tuberculosis and conditionally pathogenic mycobacteria (Mycobacterium kansasii and Mycobacterium avium). The replacement of oxygen by sulfur in 3-phenyl-6,8-dichloro-2H-1,3-benzoxazine-2.4(3H)-diones and 3-arylquinazoline-2,4(1H,3H)-diones gave rise to an increase of antimycobacterial activity. The most active compound was 3-(3-chlorophenyl)-6,8-dichloro-2H-1,3-benzoxazine-2,4(3H)-dithione.

Synthesis and characterisation of a new amphotericin B-methoxypoly(ethylene glycol) conjugate.

The reaction of methoxypoly(ethylene glycol)-4-nitrophenyl carbonate with amphotericin B has been used to prepare a new conjugate of amphotericin B (mPEG-AmB). A preliminary screening of in vitro antifungal activity has suggested that mPEG-AmB possesses a similar effect and a similar spectrum of activity as the conventional amphotericin B formulated with sodium desoxycholate.

[Antimicrobial salicylanilides and 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones]. / Antimykobakteriální salicylanilidy a 3-fenyl-2H-1,3-benzoxazin-2,4(3H)-diony.

Salicylanilides and 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones are strong antimycobacterial substances which can be considered to be potential antituberculotics. In order to be able to verify the prognostics of the relationships between the structure and antimycobacterial activity, the series of previously evaluated substances was extended to include 4'-ethoxycarbonylsalicylanilide, 4'-trifluoromethylsalicylanilide, 4'-cyanidosalicylanilide, 4'-thiocarbamoylsalicylanilide, 3-(4-ethoxycarbonylphenyl)-2H-1,3-benzoxazine-2,4(3H)-dione, 3-(4-trifluoromethylphenyl)-2H-1,3-benzoxazine-2,4(3H)-dione, and 3-(4-cyanidophenyl)-2H-1,3-benzoxazine-2,4-(3H)-dione. The substances were evaluated against Mycobacterium tuberculosis, M. kansasii, and M. avium. In harmony with the previous study (see ref. 1), antimycobacterial activity increased with increasing lipophilicity and electron-acceptor properties of substituents. As the values of regression coefficients were not substantially changed after the complementation of the group, the present authors consider the problem under study to be solved.

New groups of antimycobacterial agents: 6-chloro-3-phenyl-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones and 6-chloro-3-phenyl-2H-1,3-benzoxazine-2,4(3H)-dithiones.

A series of 6-chloro-3-phenyl-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones 3 and a series of 6-chloro-3-phenyl-2H-1,3-benzoxazine-2, 4(3H)-dithiones 4 were synthesized by melting 6-chloro-3-phenyl-2H-1, 3-benzoxazine-2,4(3H)-dione and its derivatives substituted on the phenyl ring 2 with tetraphosphorus decasulfide. Compounds 2c-e, 3 and 4 exhibited in vitro activity against Mycobacterium tuberculosis, M. kansasii (two strains) and M. avium better than or comparable to that of isoniazid. Replacement of the oxo group by a thioxo group at position 4 led to improvement in activity against M. tuberculosis and M. kansasii. The Free-Wilson method and procedure developed by the authors were used to analyse the structure-activity and structure-antimycobacterial profile relationships, respectively.

[Antitubercular derivatives of quinazoline]. / Protituberkulózní deriváty chinazolinu.

The study is a review paper about the development of antituberculous substances in the group of quinazoline derivatives. Most antituberculous compounds under study contain the pertinent pharmacophores in the functional groups and their antituberculous activity cannot be considered to be specific for quinazolines. Nevertheless, several groups of antituberculously effective quinazoline derivatives were found which do not contain the known pharmacophores of antituberculous activity. The substances are, on the rule, of medium activity, but the activity of some of them, evaluated in vitro, approaches that of commonly used antituberculous agents. They can thus initiate new research in this direction. The present paper is already the 12th communication in a series of review papers about substances with antituberculous activity.

[Relation between chemical structure and antimycobacterial activity against atypical strains. XIII. Thiosalicylanilides]. / Vztahy mezi chemickou strukturou látek a jejich antimykobakteriální aktivitou vuci atypickým kmenum XIII. Thiosalicylanilidy.

On the basis of a preliminary study of antimycobacterial activity of thiobenzanilides a series of eight thiosalicylanilides have been prepared. Synthetized compounds have been examined in vitro against Mycobacterium tuberculosis, Mycobacterium kansasii, Mycobacterium avium and Mycobacterium fortuitum. All compounds have been found very active. The values of minimal inhibitory concentrations are summarized in Table 1. 3',4'-Salicylanilide was selected for the following research. The compound have been found inactive in vivo (on experimental murine tuberculosis).

Antimycobacterial activity of 3'- and 4'-fluorothiobenzanilides.

On the basis of a preliminary study of the antimycobacterial activity of thiobenzanilides, a group of 3'-fluoro- and 4'-fluorothiobenzanilides has been synthesized and tested against Mycobacterium tuberculosis, M. kansasii, M. avium and M. fortuitum. The results of this study demonstrate that electron withdrawing groups increase the activity of thiobenzanilides and fluoro benzothioanilides against atypical strains which is higher then that of INH.

Relationships between the chemical structure of antimycobacterial substances and their activity against atypical strains. Part 14: 3-Aryl-6,8-dihalogeno-2H-1,3-benzoxazine-2,4(3H)-diones.

A set of eight derivatives of 6,8-dichloro-3-phenyl-2H-benzoxazine-2,4(3H)-dione and nine derivatives of 6,8-dibromo-3-phenyl-2H-1, 3-benzoxazine-2,4(3H)-dione, substituted on the phenyl ring, was prepared by the reaction of the corresponding salicylanilides with ethyl chloroformate. The compounds were evaluated in vitro for antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium kansasii, and Mycobacterium avium. Their activity increases with increasing hydrophobicity and electron-withdrawing ability of the substituents on the phenyl ring.

[Biological effects of substances similar to salicylanilides benzanilides]. / Biologické úcinky látek podobných salicylanilidum benzanilidy.

The present review paper is the first collected communication about biological activity of benzanilides. The substances of the above-mentioned structures show a number of activities (antibacterial, ref. 1-22; antituberculous, ref. 23-25; antimycotic, ref. 26-95; antiviral, ref. 96-98, antiprotozoan, ref. 97; anthelmintic, ref. 37, 99-100; insecticidal, ref. 31, 37, 101-104; herbicidal, ref. 106-130, antitumour, ref. 131-137; immunosuppressive, ref. 134, 138; hypnotic, ref. 140; anticonvulsive, ref. 141-151, anti-inflammatory, ref. 152; local-anaesthetic, ref. 155-156; antiarrhythmic, ref. 155, 158; vasodilating, ref. 159; antiulcerative, ref. 160; anti-androgenic, ref. 161; hypoglycemic ref. 162). Only very few of them have been hitherto introduced into practice. Papers investigating biological activity of benzanilides can be encountered also at present.

[Biological effects of substances similar to salicylanilides. 3-aryl-2H, 4H-benz(e)(1,3)oxazine-2, 4-diones and thiosalicylanilides]. / Biologické úcinky látek podobných salicylanilidum. 3-aryl-2h, 4h-benz(e)(1,3)oxazin-2, 4-diony a thiosalicylanilidy.

The review paper is the first collected communication about the biological activity of 3-aryl-2H,4H-benz(e)(1,3)oxazine-2,4-diones and thiosalicylanilides. The substances of the above mentioned structures show a number of biological activities (antibacterial, antituberculous, antimycotic, anthelmintic, molluscocidal, neuroleptic, analgesic and anti-inflammatory) which can be modelled by structural changes. Only very few of them have been hitherto introduced into practice as anthelmintic agents, or agents with a special purpose (destroying the sea lamprey in Canadian lakes). In the group of 3-aryl-2H,3H-benz(e)(1,3)-oxazine-2,4-diones, i.e. substances developed from salicylanilides by the action of alkyl-chloroformiates, antibacterial activity is reported in refs. 3-12, antituberculous activity in refs. 13, 14, antimycotic activity in refs. 5, 6, 9, 12, 15, 16, anthelmintic activity in refs. 6,917-20, molluscocidal activity in refs. 6, 21, analgesic and anti-inflammatory activity in refs. 22-24, herbicidal activity in refs. 25, 26, allergenic activity in ref. 27. In the group of salicylanilides, antibacterial activity is reported in refs. 28-37, antimycotic activity in refs. 28-36, antiprotozoal activity in ref. 35, anthelmintic activity in refs. 28-40, 49, molluscocidal activity in refs. 7, 28-36. The present paper furthermore sums up the papers concerned with the toxicities of the above-mentioned agents. Though the peak of research of the groups of the above-mentioned structure was in the 1960s and 1970s, papers investigating their biological activity can be encountered also at present.