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. 2017 Nov 18;5(1):15.
doi: 10.1007/s40203-017-0034-0. eCollection 2017.

Molecular docking analysis of curcumin analogues against kinase domain of ALK5

Shivananda Kandagalla  1 , B S Sharath  1 , Basavapattana Rudresh Bharath  2 , Umme Hani  1 , Hanumanthappa Manjunatha  1
Affiliations

Molecular docking analysis of curcumin analogues against kinase domain of ALK5

Shivananda Kandagalla et al. In Silico Pharmacol. .

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-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 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.

Keywords: ALK5; Autodock Vina; Curcumin; Curcumin analogues; EMT; Metastasis; TGF-β.

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Conflict of interest statement

All authors declared that they have no competing interest.

Figures

Fig. 1
Fig. 1
Molecular docking study: Ligand as ball and stick (1B. S4; 2B. S5; 3B. S6; 4B. S30; 5B. S58; 6B.S59) at the binding pocket of ALK5 receptor
Fig. 2
Fig. 2
Metabolic site of lead molecules: NOR indicates the Normalized Occurrence Ratio; a high NOR indicates a more commonly reported site of metabolism in the metabolite database. The atoms are colored according to the chances of a metabolic site; No data: grey, Very low: Not colored, Low: green, Medium: orange and High: red
See this image and copyright information in PMC

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