In silico drug-likeness, biological activity and toxicity prediction of new 3,5-bis(hydroxymethyl)tetrahydro-4H-pyran-4-one derivatives
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.
2 Bazhykova KB, Langer P, Yergaliyeva EM, Seylkhanov TM, Abilov ZA (2018) Chem Bull Kaz Nat Univ 4:4-9. Crossref
3 Bazhykova KB, Yergaliyeva EM, Abduali GA, Mukhan D N, Abik NA, Otynshiyev EB (2019) New Materials, Compounds and Applications 3:47-51
4 Bazhykova KB, Yergaliyeva EM, Langer P (2021) Synthesis of 3,5-bis(hydroxymethyl)tetrahydro-4H-pyran-4-one and its derivatives [Sintez 3,5-bis(gidroksimetil)tetragidro-4H-piran-4-ona i ego proizvodnyh]. Abstracts of the scientific conference “Fine organic synthesis-2021”, Almaty, Kazakhstan. P.18. (In Russian)
5 Li W, Su ZY, Guo Y, Zhang C, Wu R, et al. (2018) Chem Res Toxicol 31:88-96. Crossref
6 Chainoglou E, Hadjipavlou-Litina D (2019) Expert Opin Drug Dis 14:821-842. Crossref
7 Kuhnert R, Sárosi MB, George S, Lönnecke P, Hofmann B, et al. (2019) ChemMedChem 14:255-261. https://doi.org/10.1002/cmdc.201800651
8 Weires NA, Slutskyy Y, Overman LE (2019) Angew Chem Int Edit 58:8561-8565. Crossref
9 Devi N, Borthakur U, Saikia AK (2021) Studies in Natural Products Chemistry 70:265-312. Crossref
10 Molinspiration (2022) Calculation of molecular properties and bioactivity score. URL
11 Filimonov DA, Lagunin AA, Gloriozova TA, Rudik AV, Druzhilovskii DS, et al. (2022) Chem Heterocyc Compd 50:444-457. Crossref
12 Banerjee P, Eckert OA, Schrey AK, Preissner R (2022) ProTox-II Prediction Of Toxicity Of Chemicals. URL
13 ACD/ChemSketch, version 2021.2.0 (2022) Advanced Chemistry Development, Inc., Toronto, Canada. URL
14 Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (1997) Adv Drug Deliver Rev 23:3-25. Crossref
15 Tyagi M, Begnini F, Poongavanam V, Doak BC, Kihlberg J (2020) Chem-Eur J 26:49-88. Crossref
16 Poongavanam V, Doak BC, Kihlberg J (2018) Curr Opin Chem Biol 44:23-29. Crossref
17 Protti ÍF, Rodrigues DR, Fonseca SK, Alves RJ, de Oliveira RB, Maltarollo VG (2021) ChemMedChem 16:1446-1456. Crossref
18 Jablonsky M, Haz A, Burcova Z, Kreps F, Jablonsky J (2019) BioResources 14:6294-6303.
19 Jablonsky M, Haz A, Burcova Z, Kreps F, Jablonsky J (2020) J Comput Biol 17:1397-1406. Crossref
20 Ibrahim MA, Abdelrahman AH, Hussien TA, Badr EA, Mohamed TA, et al. (2020) Comput Biol Med 126:104046. Crossref
21 Ritzén A, David L (2019) Successful Drug Discovery 4:35-53. Crossref
22 Ovalle-Magallanes B, Navarrete A, Haddad PS, Tovar AR, Noriega LG, et al. (2019) Phytomedicine 58:152891. Crossref
23 Akıncıoğlu H, Gülçin İ (2020) Mini Rev Med Chem 20:703-715. Crossref
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