[Changes in basic nitrogen in a group of potential new beta- adrenolytics--derivatives of p-hydroxyacetophenone and p-hydroxypropiofenone]. / Obmeny na bázickom dusíku v skupine nových potenciálnych betaadrenolytík--derivátov p-hydroxyacetofenónu a p-hydroxypropiofenónu.

Within the relationship of the structure and effect of new beta-adrenolytic agents derivatived from p-hydroxyacetophenone and p-hydroxypropiophenone with a propoxymethyl group in the lipophilic part of the molecule and with a propanamine, a butanamine and a pyrrolidine in the side-chain were studied. In order to prepare these substances, a procedure was selected from several tested ones, in which 4-hydroxy-3propoxymethylphenylketone were treated with chloromethyloxirane and subsequent reaction a hydrobromic acid were prepared 4-(3-brom-2-hydroxypropoxy)-3-propoxymethylalkylketone. Final substances were prepared reaction with amine. The structure of prepared compounds was confirmed on the basic interpretation of the IR, UV and 1H NMR spectra. The results of pharmacological evaluation of selected compounds showed a significant beta 1-blocking activity lower than acebutolol. Their local anesthetic activity is low according with their partition coefficients. The characteristic of the prepared compounds was supplemented by the determination of their partition coefficients, surface tension, dissociation constants and acute toxicity.

[Derivatives of para-hydroxyacetophenone and para-hydroxypropiophenone as a potential new beta-adrenolytic agent]. / Deriváty para-hydroxyacetofenónu a para-hydroxypropiofenónu ako nové potenciálne beta-adrenolytiká.

Within the framework of the study of the structure-effect relationship, a series of novel potential beta-adrenolytic agents derived from p-hydroxyacetophenone and p-hydroxypropiophenone with an alyloxymethyl and a cycloalkyloxymethyl group in the lipophilic part of the molecule and an isopropyl and a tert-butyl group in the hydrophilic part on the basic nitrogen were prepared by means of a well-tried method. The structure of the prepared drugs was confirmed on the basis of interpretation of the IR, UV, 1H-NMR and mass spectra. The results of pharmacological evaluation of selected drugs show that the agents poses beta-adrenolytic and antiarrhythmic activity. From the viewpoint of comparison of the individual drugs subjected to testing the presence of an alyl seems more advantageous than that of a cyclohexyl. The characteristic of the prepared drugs was supplemented by the determination of their partition coefficients, surface tension and acute toxicity.

Influence of some synthetic antioxidants on the growth and metastases formation of Lewis lung carcinoma and amelanotic B16 melanoma in C57BL mice.

Synthetic antioxidants: EPO (p-ethoxyphenol), PHP (p-hydroxypropiophenone), and DPPD (N,N'-diphenyl-p-phenylenediamine) dissolved in dimethylsulfoxide were administered subcutaneously to mice after subcutaneous implantation of Lewis lung carcinoma or amelanotic B16 melanoma into the tails. The doses of antioxidants used were: 50 mg/kg, 100 mg/kg, and 200 mg/kg per day, respectively. The animals received five injections a week during two weeks. The tails with Lewis lung carcinoma were amputated after 16 days and with amelanotic melanoma after 20 days; tumors weight was measured. 25 days after Lewis lung carcinoma and 42 days after B16 melanoma implantation mice were sacrificed, lungs weighed and incidence of pulmonary and extrapulmonary metastases were estimated. There was a significant increase of weight of amelanotic melanoma in animals treated with EOP or PHP (p less than or equal to 0.05). No influence of antioxidants on the metastases incidence of B16 melanoma was found. Antioxidants used did not influence the Lewis lung carcinoma weight, whereas EOP or PHP increased the incidence of extrapulmonary metastases (p = 0.05, and p = 0.1, respectively).