Dataset Information

Synthesis, Anticancer Evaluation, Computer-Aided Docking Studies, and ADMET Prediction of 1,2,3-Triazolyl-Pyridine Hybrids as Human Aurora B Kinase Inhibitors.

ABSTRACT: A novel series of 1,2,3-triazolyl-pyridine hybrids were prepared through the reaction of the triazole derivative (1) with the appropriate aldehyde (2a-g) and malononitrile or ethyl cyanoacetate in the presence of ammonium acetate in refluxed acetic acid. The chemical composition of the products was established on the basis of spectral and elemental analyses. Aurora B kinase is a protein with diverse biological actions in controlling tumorigenesis by inhibiting apoptosis and promoting proliferation and metastasis, making it an emerging target for diseases such as hepatocellular carcinoma (HCC). Alteration in the target protein expression causes unequal distribution of genetic information, causing HCC. The new compounds were tested for their antihepatic cancer activity, and some of them had strong efficacy against human hepatoblastoma (HepG2) cell lines.

SUBMITTER: Rashdan HRM

PROVIDER: S-EPMC7818638 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Synthesis, Anticancer Evaluation, Computer-Aided Docking Studies, and ADMET Prediction of 1,2,3-Triazolyl-Pyridine Hybrids as Human Aurora B Kinase Inhibitors.

Rashdan Huda R M HRM Shehadi Ihsan A IA Abdelmonsef Abobakr H AH

ACS omega 20210105 2

A novel series of 1,2,3-triazolyl-pyridine hybrids were prepared through the reaction of the triazole derivative (<b>1</b>) with the appropriate aldehyde (<b>2a-g</b>) and malononitrile or ethyl cyanoacetate in the presence of ammonium acetate in refluxed acetic acid. The chemical composition of the products was established on the basis of spectral and elemental analyses. Aurora B kinase is a protein with diverse biological actions in controlling tumorigenesis by inhibiting apoptosis and promoti ...[more]

PMID: 33490804

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Project description:mPGES-1 is an enzyme, which, when activated by inflammatory factors, can cause prostaglandin E synthesis. Traditional non-steroidal anti-inflammatory drugs are capable of inhibiting prostaglandin production, yet they can also cause gastrointestinal reactions and coagulation disorders. mPGES-1, the enzyme at the conclusion of prostaglandin production, does not cause any adverse reactions when inhibited. Numerous studies have demonstrated that mPGES-1 is more abundant in cancerous cells than in healthy cells, indicating that decreasing the expression of mPGES-1 could be a potential therapeutic strategy for cancer. Consequently, the invention of mPGES-1 inhibitors presents a fresh avenue for the treatment of inflammation and cancer. Incorporating a database of TCM compounds, we collected a batch of compounds that had an inhibitory effect on mPGES-1 and possessed IC50 value. Firstly, a pharmacophore model was constructed, and the TCM database was screened, and the compounds with score cut-off values of more than 1 were retained. Then, the compounds retained after being screened via the pharmacodynamic model were screened for docking at the mPGES-1 binding site, followed by high-throughput virtual screening [HTVS] and standard precision [SP] and super-precision [XP] docking, and the compounds in the top 20% of the XP docking score were selected to calculate the total free binding energy of MM-GBSA. The best ten compounds were chosen by comparing their score against the reference ligand 4U9 and the MM-GBSA_dG_Bind score. ADMET analysis resulted in the selection of ten compounds, three of which had desirable medicinal properties. Finally, the binding energy of the target protein mPGES-1 and the candidate ligand compound was analyzed using a 100 ns molecular dynamics simulation of the reference ligand 4U9 and three selected compounds. After a gradual screening study and analysis, we identified a structure that is superior to the reference ligand 4U9 in all aspects, namely compound 15643. Taken together, the results of this study reveal a structure that can be used to inhibit mPGES-1 compound 15643, thereby providing a new option for anti-inflammatory and anti-tumor drugs.

Dataset Information

Synthesis, Anticancer Evaluation, Computer-Aided Docking Studies, and ADMET Prediction of 1,2,3-Triazolyl-Pyridine Hybrids as Human Aurora B Kinase Inhibitors.

Publications

Synthesis, Anticancer Evaluation, Computer-Aided Docking Studies, and ADMET Prediction of 1,2,3-Triazolyl-Pyridine Hybrids as Human Aurora B Kinase Inhibitors.

Similar Datasets

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