Bioinformatics and Cheminformatics Study of Carbazole Derivatives – P3c7, P3c7-A20 P3c7-S243, and De Novo 2,5-Disubstituted 1,3,4-Oxadiazole Derivatives

Abstract

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. RezumatRecent, au fost menționate efectele neuroprotectoare ale câtorva derivați de carbazol, dar fară stabilirea unui mecanism molecular de acțiune clar. În acest articol, utilizând instrumente biologice computaționale, am propus caracteristicile farmacodinamice ale derivaților de novo 2,5 disubstituiți ai 1,3,4-oxadiazolului, comparativ cu P3C7, P3C7-A20 P3C7-S24, cunoscute deja sub formă de compuși neuroprotectori. În plus, pentru acești compuși, au fost stabilite profilurile farmacocinetice (ADME-Tox), incluzând absorbția, distribuția, metabolismul, excreția și toxicologia. Rezultatele noastre de calcul au arătat că: (i) compușii de novo 1b, 1c și 1d au prezentat activitate biologică pe nicotinamidă fosforibosiltransferază, care presupune că acești compuși au efecte neuroprotectoare, în mod similar cu P3C7-A20; (ii) rezultatele ADME-Tox, cu accent pe toxicitate și permeabilitățile BBB și SNC, arată că derivatul 1c ar putea fi un candidat adecvat pentru un nou medicament. Rezultatele noastre de calcul au propus derivații de novo 2,5-disubstituiți ai 1,3,4-oxadiazolului 1a-d, în special 1c, ca noi candidați pentru efectele lor neuroprotectoare.

In Silico and Experimental Investigation of the Biological Potential of Some Recently Developed Carprofen Derivatives

“…Recently, we reported in our previous papers the synthesis and structural, biological and bioinformatics characterization of new derivatives based on carprofen scaffolds [20][21][22][23][24][25].…”

Recent Advances in the Study of Derivatives of (Ez)-N’- Benzylidene-(2rs)-2-(6-Chloro-9h-Carbazol-2-Yl) Propanohydrazide

“…Starting from the chemical structure of caprofen, following structural modulations, derivatives of (EZ)-N'-benzylidene-(2RS)-2-(6-chloro-9H-carbazol-2-yl) propanohydrazide (1a-f) were obtained; we presented in our published articles [2,9] the synthesis and confirmation of the structure of these original compounds, realized by IR and NMR spectral experiments The obtaining of new derivatives was based on the principles of "green chemistry", a concept that represents the design, development and implementation of chemical products and processes, in order to reduce or eliminate the use and formation of substances dangerous to human health and the environment.…”