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. 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.

[New antifungal substances from a group of guanidine derivatives]. / Nové antifungální látky ze skupiny derivátu guanidinu.

Diseases caused by fungi represent an emphatic problem both in medicine and agriculture. The review of the latest knowledge in the group of guanidine derivatives, which are divided into two main series--into compounds with aliphatic and cyclic substituents, was carried out within the research of new compounds with this activity.

Antimycobacterial 3-aryl-2H-1,3-benzoxazine-2,4(3H)-diones.

A series of 153 derivatives of 3-phenyl-2H-benzoxazine-2,4(3H)-dione substituted in position 6 or 7 on benzoxazine and on the phenyl ring was synthesized. The compounds were evaluated in vitro for antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium kansasii and Mycobacterium avium. The activity of the compounds increases with increasing hydrophobicity and electron-withdrawing properties of the substituents on the phenyl ring, whereas the effect of the substituents on the benzoxazine ring seems to be more complex.

A case of carcinoma rete testis: histomorphological, immunohistochemical and ultrastructural findings and review of literature.

A 72-year-old man presenting with a secondary hydrocoel underwent orchidectomy. Gross examination revealed a tumor arising in the region of the rete testis, which on histopathology proved to be a papillary adenocarcinoma. The patient did not have evidence of any other neoplasia elsewhere in the body. The lesion fulfilled the anatomic criteria elucidated by Nochomovitz et al to be labelled as adenocarcinoma of Rete testis. Electron microscopy revealed characteristic nuclear infoldings and microtubules with two different arrangements. The tubules were either seen to form concentric circles or were in irregular groups with filaments interspersed. The lesion on immunohistochemistry was negative for germ cell markers AFP and HCG, and was positive for cytokeratin and epithelial membrane antigen. A review of literature is also presented.

Combination of molecular modeling and quantitative structure-activity relationship analysis in the study of antimycobacterial activity of pyridine derivatives.

A set of 4-benzylsulfanyl derivatives of pyridine-2-carbonitriles and pyridine-2-carbothioamides, previously tested for their antimycobacterial activity, were analysed by quantitative structure-activity relationship (QSAR) techniques, using some physicochemical and quantum-chemical parameters. The resulting QSAR revealed that the activity increases with electron withdrawing substituents in the benzyl moiety of studied compounds. HOMO orbitals can play an important role in the description of the mechanism of interactions at the molecular level. Additionally, the results of multiple linear regression indicate the differences between Mycobacterium tuberculosis and M. avium. The hydrophobicity of studied compounds is important for activity against M. avium.

Conformational analysis of 2-hydroxy-2',5'-diazachalcones.

Spatial arrangement of 2-hydroxy-2',5'-diazachalcones was studied by means of infrared and NMR spectral data and molecular models calculations. The models were calculated in vacuum using semi-empirical AM1 method (software HyperChem 5.1). The initial geometries of the molecules were built by means of standard parameters and then optimized by Polak-Ribiere geometrical optimization. It was found that (E)-s-cis-conformers with synperiplanar arrangement of C-alpha and C-6 have the lowest heats of formation (standard heat of formation).

[Antitubercular agents. LIV. 3-Alkyl(or -alkyl) thio-2,5-pyrazindicarboxamides]. / Antituberkulotika. LIV. 3-Alkyl(resp.aryl)thio-2,5-pyrazindikarboxamidy.

From 5-cyano-3-chloro-2-pyrazinecarboxamide) (II) hydrolysis in acid medium) yielded 3-chloro-2,5-pyrazinedicarboxamide (III), which in a reaction with sodium hydrogensulfide in dimethyl-formamide) yielded 3-mercapto-2,5-pyrazinedicarboxamide (IV). This compound through condensations with alkyl- and arylhalogenides in triethylamine) yielded 3-alkyl(or aryl) thio-2,5-pyrazinedicarboxamides of type I. The structure of compounds was confirmed by elemental analysis, IR and 1H NMR spectra. A microbiological evaluation was carried out; the antituberculous effect of these compounds is not higher than that of pyrazinamide.

[Quantitative structure-activity analysis of thiobenzamides]. / Quantitative Struktur-Wirkungs-Analyse der Thiobenzamide.

It is very difficult to meet all prerequisites for the optimization of the tuberculostatic action of thiobenzamides. On the one hand, a strongly polarized C=S bond of the thiocarbamido group is necessary, and on the other hand, the value of the Hammett constant must be positive (to prevent hepatotoxicity). The conjugated system can be extended to reduce the excitation energy of the eta-eta electronic transition. However, the lipophilicity should not be overincreased (to avoid the risk of increased antimitotic activity and acute toxicity). Of the culture media, the Sauton system seems to be best suited since it is the most simple. However, the culture medium according to Sula comes closest to in vivo conditions as it contains proteins and is devoid of surfactants.