Lipinski’s Rule of Five and Drug Likeness Scores

A series of new 10- (alkylamino) -8-methyl-2,6-dihydroimidazo [1,2 - c] pyrimido [5,4 - e] pyrimidin - 5 (3H) - thione (4a - g) Predictions (drug-like, lipophilic and solubility parameters) were made using Osiris Property Explorer, ALOGPS 1, Molinspiration and ACD / Chemsketch 12.0 software program. The drug-related properties of the calculated design molecules are similar to those found in most commercial drugs. Among the proposed analogs, four promising candidates (4 a - d) were selected for synthesis based on Lipinski's "five rules" and drug similarity scores.

According to Lipinsky Rule 5, the molecular weight of the active plant compound, log p, the number of hydrogen bond donors and hydrogen bond acceptors are listed in Table 1. Of the 35 Lipinski fulfill the five rules, there are 21 ligands. Compounds for docking with Pi3K and NF-kB are selected based on their toxicity. Table 2 shows ADMET (absorption, distribution, excretion, metabolism, toxicity) characteristics of compounds satisfying Lipinski properties. Many compounds are not commercially available because they are toxic after being approved. After 21 plant compounds were screened, five compounds were selected for docking studies, ie, alixin, eugenol, capsaicin, peperine and niadimicin.

Results: We chose 35 plant compounds with anticancer properties. Five compounds, ie, axin, capsaicin, eugenol, clothianidin and piperine were screened using Lipinski 5 and ADMET. These five compounds docked with PI3K and NF-kB proteins. All five ligands showed interaction with the two proteins, and the residues showed the greatest interaction between Pi3K and NF-κB, respectively. Nyadimycin shows the greatest interaction between PI3K and NF - κB. Conclusion: Computer docking experiments demonstrated that plant compounds effectively inhibiting the target protein can be identified efficiently. Interestingly, we found that niadimicin is a plant compound of Moringa Olay Fellow showing its greatest interaction with the target protein because its medicinal ingredient has not yet been fully developed. We also found that the enzyme Cys 37 plays an important role in hydrogen bonding with inhibitors.