Determination of hydrolytic stability and acute toxicity of previously synthesized pyrrole-based hydrazones

personАвтори: A. Bijev, I. Nikolova, M. Georgieva, N. Danchev

Abstract Appropriate pyrrole derivative, containing susceptible to hydrolysis hydrazone group, was chosen to represent a series of inhibitors of M. tuberculosis. The model compound was incubated at 37oC in mixtures of dioxane : buffer (pH of 1.2, 7.0 and 9.0) and  aliquot samples were drawn at definite time intervals. The absorbance at 282 nm was measured to determine possible hydrolytic cleavage of the hydrazone group. No change was detected at pH=7.0, whereas a decrease in the absorption was observed at pH = 1.2 and pH=9.0. The results witness for a chemical stability of the model compound at moderate pH and temperatures, but for a sensibility to acidic or low alkali media. The acute intraperitoneal and per oral toxicities were also investigated, and the corresponding Indexes of Resorbtion (IR) were calculated for a selected group of representative compounds. The evaluated structures were proved to be 7-10 times less toxic than the reference Isoniazid. For most of the structures the calculated IR was 50%, but there were some with higher IR up to 60%.

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