RESUMEN
Various means for levorin isolation were studied with the EPR method and approaches to stabilization of the antibiotic on storage under natural conditions were discussed. It was shown that formation of the radicals begins already at the first stage of the antibiotic isolation, i.e. during extraction from the mycelium. Treatment of the solvents with an inert gas or addition of antioxidants decreased the number of free radicals in a freshly isolated product. The antibiotic inactivation rate depended on the initial concentration of the free radicals and conditions of natural storage. The levorin stability increased when oxygen was thoroughly removed from the solvents at all isolation stages and the antibiotic was subsequently stored under conditions preventing any access of the air. The stabilizing effect was also observed when the oxidative effect of the amino sugar moiety on destruction of the polyenic chromophore during the antibiotic complex formation with respect to the amino group was decreased.
Asunto(s)
Antibacterianos/antagonistas & inhibidores , Antifúngicos/farmacología , Candicidina/farmacología , Polienos/antagonistas & inhibidores , Candicidina/antagonistas & inhibidores , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Espectroscopía de Resonancia por Spin del Electrón , Radicales Libres , TemperaturaRESUMEN
Changes in the acid-base characteristics of levorin during its inactivation are discussed. It is shown that with a decrease in the biological activity a change in the basic characteristics of the levorin amino sugar moiety takes place. The kinetic studies with model compounds, i. e. octaenic alcohol and glucosamine showed that the processes of their oxidation were interrelated. Oxidation of the amino sugar played the role of an inducing factor in oxidation of the polyenic chromophore and in addition impaired correlation between the extinction specific coefficient of levorin and its biological activity.
Asunto(s)
Amino Azúcares/metabolismo , Antibacterianos/antagonistas & inhibidores , Polienos/antagonistas & inhibidores , Antibacterianos/metabolismo , Candicidina/antagonistas & inhibidores , Candicidina/metabolismo , Técnicas In Vitro , Cinética , Matemática , Oxidación-Reducción , Polienos/metabolismoRESUMEN
The results of studying free radicals of some polyenic antibiotics with the EPR method are presented. It is shown that the number of free radicals increased by 100 per cent with a 2-fold decrease in the biological activity. A qualitative change in the EPR spectrum due to the presence of a new radical type was also observed. The changes in the spectral characteristics of levorin allowed one to demonstrate that breaking of the links and formation of the polymer products during oxidative destruction of the polyenic chromophore resulted from attachment of the radicals through the antibiotic double bonds. The data correlate with the results of the quantum-chemical evaluation of the polyenic chromophore.
Asunto(s)
Antibacterianos/antagonistas & inhibidores , Antifúngicos/antagonistas & inhibidores , Candicidina/antagonistas & inhibidores , Polienos/antagonistas & inhibidores , Antibacterianos/análisis , Candicidina/análisis , Fenómenos Químicos , Química Física , Cromatografía en Gel , Espectroscopía de Resonancia por Spin del Electrón , Radicales Libres , Polienos/análisisRESUMEN
The inactivation process of levorin, a polyenic antibiotic was studied in the presence of oxygen. It was found that the biological activity did not sufficiently correlate with the optical density of the antibiotic solution. This indicates that destruction of the double bonds was not the only process resulting in the biological activity loss. In this connection methods for qualitative determination of the levorin main functional groups, i.e. aromatic and aliphatic amines and carbonyl groups were developed. The methods were used for the control of the changes in these functional groups on levorin inactivation. It was found that the inactivation level was directly proportional to the amount of the oxygen absorbed, 1 molecule of oxygen being required for inactivation of 2 levorin molecules. The number of the carbonyl groups and aromatic amines did not change during the inactivation process. In the first stages of inactivation the biological activity was directly proportional to the level of amino sugars. If the heptaen chromophore is not absorbed, 3 double bonds remain in inactivated levorin.
Asunto(s)
Antifúngicos/antagonistas & inhibidores , Candicidina/antagonistas & inhibidores , Polienos/antagonistas & inhibidores , Candicidina/análisis , Fenómenos Químicos , Química , Oxidación-Reducción , Relación Estructura-ActividadRESUMEN
The kinetics of peroxide formation in the process of levorin and mycoheptin oxidation at a temperature of 57 degrees C was studied. It was shown that the peroxide compounds actively participated in the processes of levorin and mycoheptin inactivation as intermediate products of their transformation. Addition of the peroxides increased the rate of the antibiotic degradation even if there was no oxygen and subsequently decreased the periods of their storage. Conditions for the use of the iodometric method for determination of the peroxides in the poyenic compounds are discussed.