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Synthesis and toxicological evaluation of newly synthesized 7,8-disubstituted theophylline derivatives | Abstract

Der Pharma Chemica
Journal for Medicinal Chemistry, Pharmaceutical Chemistry, Pharmaceutical Sciences and Computational Chemistry

ISSN: 0975-413X
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Abstract

Synthesis and toxicological evaluation of newly synthesized 7,8-disubstituted theophylline derivatives

Author(s): Maya B. Georgieva, Magdalena S. Kondeva-Burdina, Javor I. Mitkov, Virginia I. Tzankova, Georgi T. Momekov and Alexander B. Zlatkov

Four new 7,8-disubstituted theophylline derivartives were synthesized. Their purity was elucidated with melting points and TLC characteristics. The structure of the obtained compounds was proven by IR, 1H NMR and 13C NMR spectral data. The cytotoxicity, the in vitro effects on sub-cellular and cellular level and the antiproliferative activity of the synthesized compounds was evaluated. On isolated rat microsomes only 7d showed statistically significant toxic effect. It increased the production of malondialdehyde by 52 % compared to the control. On isolated rat hepatocytes 7b was outlined as the least toxic structure, while 7d expressed highest toxicity, when compared to theophylline. Within the series only 7a proved to be the most active antiproliferative agent, albeit at high micromolar concentrations.


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