In silico drug-likeness, biological activity and toxicity prediction of new 3,5-bis(hydroxymethyl)tetrahydro-4H-pyran-4-one derivatives

Keywords: tetrahydropyran-4-one, bioavailability, drug-likeness, biological activity, toxicity, PASS


This paper presents the results of predicting drug-likeness, biological activity, and toxicity for 8 new derivatives of 3,5-bis(hydroxymethyl)tetrahydro-4H-pyran-4-one using bioinformatic methods. The physicochemical and pharmacokinetic parameters of the studied compounds were determined, in silico screening for biological activity and prediction of their toxicity were carried out. Physicochemical and pharmacokinetic parameters were evaluated using the Molinspiration Cheminformatics service. It was found that compounds 1–11 corresponded to Lipinski’s rule for drug-like compounds. As predicted in Molinspiration, compound 4 exhibits significant biological activity as a possible enzyme inhibitor and G-protein coupled receptor ligand. Compound 6 is active as an ion channel modulator. Virtual PASS screening identified compounds with potential antidiabetic activity (1–3, 5–8) and activity in the treatment of phobic disorders and dementias (1–5, 7, 8, 11). Compound 1 can potentially act as a substrate for CYP2H, and inhibitors of enzymes of the peptidase group are 1, 3, 4, 6, 7, 11. As a result of QSAR prediction based on LD50 values calculated in ProTox-II, compound 10 belongs to class 6; compounds 1–3, 5 and 8 belong to the 5th class of toxicity; compounds 6 and 9 belong to the 4th class. Compound 4 belongs to class 3. Compounds 1–9 do not exhibit the toxicities shown in the ProTox-II models. Compounds 10 and 11 may be carcinogenic.


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How to Cite
Yergaliyeva, E., Bazhykova, K., Abeuova, S., Vazhev, V., & Langer, P. (2022). In silico drug-likeness, biological activity and toxicity prediction of new 3,5-bis(hydroxymethyl)tetrahydro-4H-pyran-4-one derivatives. Chemical Bulletin of Kazakh National University, 107(4), 14-20.