Dataset Information

Molecular docking analysis of curcumin analogues against kinase domain of ALK5.

ABSTRACT: During metastasis, cancer cells transcend from primary site to normal cells area upon attaining epithelial to mesenchymal transition (EMT) causing malignant cancer disease. Increased expression of TGF-? and its receptor ALK5 is an important hallmark of malignant cancer. In the present study, efficacy of curcumin and its analogues as inhibitors of ALK5 (TGF?R-I) receptor was evaluated using in silico approaches. A total of 142 curcumin analogues and curcumin were retrieved from peer reviewed literature and constructed a combinatorial library. Further their drug-likeness was assessed using Molinspiration, cheminformatics and preADMET online servers. The interaction of 142 curcumin analogues and curcumin with ALK5 receptor was studied using Autodock Vina. This study revealed six curcumin analogues as promising ALK5 inhibitors with significant binding energy and H-bonding interaction.

SUBMITTER: Kandagalla S

PROVIDER: S-EPMC5755696 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Molecular docking analysis of curcumin analogues against kinase domain of ALK5.

Kandagalla Shivananda S Sharath B S BS Bharath Basavapattana Rudresh BR Hani Umme U Manjunatha Hanumanthappa H

In silico pharmacology 20171118 1

During metastasis, cancer cells transcend from primary site to normal cells area upon attaining epithelial to mesenchymal transition (EMT) causing malignant cancer disease. Increased expression of TGF-β and its receptor ALK5 is an important hallmark of malignant cancer. In the present study, efficacy of curcumin and its analogues as inhibitors of ALK5 (TGFβR-I) receptor was evaluated using in silico approaches. A total of 142 curcumin analogues and curcumin were retrieved from peer reviewed lite ...[more]

PMID: 29308351

Similar Datasets

Project description:With 19.3 million new cases and almost 10 million deaths in 2020, cancer has become a leading cause of death today. Curcumin and its analogues were found to have promising anticancer activity. Inspired by curcumin's promising anticancer activity, we prepared three semi-synthetic analogues by chemically modifying the diketone function of curcumin to its pyrazole counterpart. The curcumin analogues (3a-c) were synthesized by two different methods, followed by their DFT analyses to study the HOMO/LUMO configuration to access the stability of compounds (∆E = 3.55 to 3.35 eV). The curcumin analogues (3a-c) were tested for antiproliferative activity against a total of five dozen cancer cell lines in a single (10 µM) and five dose (0.001 to 100 µM) assays. 3,5-Bis(4-hydroxy-3-methoxystyryl)-1H-pyrazole-1-yl-(phenoxy)ethanone (3b) and 3,5-bis(4-hydroxy-3-methoxystyryl)-1H-pyrazole-1-yl-(2,4-dichlorophenoxy)ethanone (3c) demonstrated the most promising antiproliferative activity against the cancer cell lines with growth inhibitions of 92.41% and 87.28%, respectively, in a high single dose of 10 µM and exhibited good antiproliferative activity (%GIs > 68%) against 54 out of 56 cancer cell lines and 54 out of 60 cell lines, respectively. The compound 3b and 3c demonstrated the most potent antiproliferative activity in a 5-dose assay with GI50 values ranging between 0.281 and 5.59 µM and 0.39 and 0.196 and 3.07 µM, respectively. The compound 3b demonstrated moderate selectivity against a leukemia panel with a selectivity ratio of 4.59. The HOMO-LUMO energy-gap (∆E) of the compounds in the order of 3a > 3b > 3c, was found to be in harmony with the anticancer activity in the order of 3c ≥ 3b > 3a. Following that, all of the curcumin analogues were molecular docked against EGFR, one of the most appealing targets for antiproliferative activity. In a molecular docking simulation, the ligand 3b exhibited three different types of interactions: H-bond, π-π-stacking and π-cationic. The ligand 3b displayed three H-bonds with the residues Met793 (with methoxy group), Lys875 (with phenolic group) and Asp855 (with methoxy group). The π-π-stacking interaction was observed between the phenyl (of phenoxy) and the residue Phe997, while π-cationic interaction was displayed between the phenyl (of curcumin) and the residue Arg841. Similarly, the ligand 3c displayed five H-bonds with the residue Met793 (with methoxy and phenolic groups), Lys845 (methoxy group), Cys797 (phenoxy oxygen), and Asp855 (phenolic group), as well as a halogen bond with residue Cys797 (chloro group). Furthermore, all the compound 3a-c demonstrated significant binding affinity (-6.003 to -7.957 kcal/mol) against the active site of EGFR. The curcumin analogues described in the current work might offer beneficial therapeutic intervention for the treatment and prevention of cancer. Future anticancer drug discovery programs can be expedited by further modifying these analogues to create new compounds with powerful anticancer potentials.

Dataset Information

Molecular docking analysis of curcumin analogues against kinase domain of ALK5.

Publications

Molecular docking analysis of curcumin analogues against kinase domain of ALK5.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets