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BIOINFORMATICS AND CHEMINFORMATICS STUDY OF CARBAZOLE DERIVATIVES – P3C7, P3C7-A20 P3C7-S243, AND DE NOVO 2,5-DISUBSTITUTED 1,3,4-OXADIAZOLE DERIVATIVES

NATALIA GUMA (TANASIEV) 1, ALEXANDRA TEODORA BORDEI (TELEHOIU) 2*, CARMEN LIMBAN 2, CĂTĂLINA SOGOR 1, LAURA MANOLIU 1, SPERANȚA AVRAM 1

1.Department of Anatomy, Animal Physiology, and Biophysics, Faculty of Biology, University of Bucharest, 36-46 M. Kogălniceanu Boulevard, 050107, Bucharest, Romania
2.Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956, Bucharest, Romania

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Recently, the neuroprotective effects of several carbazole derivatives have been mentioned, but without a clear molecular mechanism of action being established. In this article, by using computational biology tools, we proposed the pharmacodynamic features of de novo 2,5-disubstituted 1,3,4-oxadiazole derivatives, compared to P3C7, P3C7-A20 P3C7-S24, already known as neuroprotective compounds. Besides, for these compounds, were established the predicted pharmacokinetic profiles (ADME-Tox), including absorption, distribution, metabolism, excretion, and toxicology. Our computational results showed that: (i) de novo compounds 1b, 1c and 1d presented biological activity for nicotinamide phosphoribosyltransferase, which presumes that these compounds have neuroprotective effects, similarly with P3C7-A20; (ii) ADME-Tox results, with an emphasis on toxicity and BBB and CNS permeabilities, show that compound 1c could be a suitable drug candidate. Our computational results proposed de novo 2,5-disubstituted 1,3,4-oxadiazole derivatives 1a-d, in particular 1c, as new good candidates for neuroprotective effects.