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

Abstract

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.

Exploring the Therapeutic Potential of Petiveria alliacea L. Phytochemicals: A Computational Study on Inhibiting SARS-CoV-2’s Main Protease (Mpro)

“…According to Table 3 , the selected phytocompounds may act as both CYP3A4 inhibitors and substrates. This enzyme is responsible for the majority of medicinal metabolism in the human organism system [ 87 ].…”

“…Table 3. Pharmacokinetic properties and toxicity analysis of the selected drug molecules computed using the pkCSM web-tool [55,87]. According to the excretion profile, these phytocompounds can be excreted from the bloodstream in a relatively effective manner with virtually no risk of drug formation in the organism because the results of the study demonstrated that these phytochemicals had a total clearance (TC) value of 0.5 (log mL min −1 kg −1 ), with the only exception being astilbin, which had a negative value of −0.28.…”

Potential antiviral activity of eleutherine, isoeleutherine, eleuthinone and elecanacine compounds in Eleutherine palmifolia (L.) Merr against NSP3 SARS-COV-2: In silico study

“…The compounds physicochemical predictions are used to assess the similarity of the tested compounds to drugs based on the Lipinski's rule of five (Ro5).The Lipinski's Ro5 is an in silico tool for evaluating physicochemical properties, which is critical in determining drug safety prior to marketing as an identification process during pre-clinical trials. Other studies have found that, in addition to the Lipinski's Ro5 parameter, the descriptor of a test compounds physicochemical properties is topological polar surface area (TPSA) [16].…”

“…Physicochemical prediction based on The Lipinski's rule of five (Ro5) consisting of molecular weight (BM), number of hydrogen bond donor (HBD), number of hydrogen bond acceptor (HBA), oil to water partition coefficient (Log P) and number of bonds that can be rotated (Torsion) [15]. Other studies have added another descriptor of physicochemical properties, namely the topological polar surface area (TPSA) [16]. Toxicity prediction in this study used 2 programs that can be accessed online, namely ProTox-II and pkCSM.…”

“…The Lipinski's Ro5 parameter was made up of molecular weight (MW), number of hydrogen bond donors (HBD), number of hydrogen bond acceptors (HBA), oil to water partition coefficient (Log P), and the number of bonds that can be rotated (Torsion) [15]. Other research incorporated topological polar surface area (TPSA) parameters [16]. According to the results of the compounds studied, all test compounds met the Lipinski's Ro5 (Table 2).…”