Computational insights into the identification of a potent matrix metalloproteinase inhibitor from Indigofera aspalathoides to control cancer metastasis.

Matrix metalloproteinases (MMPs) are the major proteolytic enzymes which assist in regulating the metastatic process by degrading the extracellular matrix proteins. In this study, we have investigated the anti-metastatic potential of major bioactive compounds in the medicinal plant Indigofera aspalathoides targeting matrix metalloproteinases (MMP2 & MMP9) and it's in silico pharmacokinetic profiles using computational studies. Indigofera aspalathoides (Sivanar vembu in Tamil) is a renowned medicinal herb in traditional Indian medicine which contains indigocarpan, mucronulatol, indigocarpan diacetate, erythroxydiol X and erythroxydiol Y as the major constituents. The 3-dimensional structure of MMP2 and MMP9 was designed by using I-tasser and Modeller and it was validated by PROCHECK. The structures of mucronulatol and indigocarpan have been retrieved from PubChem and indigocarpan diacetate, erythroxydiol X & Y were drawn by using Chemdraw Ultra 6.0. Batimastat was used as a positive control. Molecular docking was performed by using AutoDock 4.2 tools and AutoDock vina, an open-source program which signifies an effective interaction between the phytoligands and MMP2 & MMP9. From the results, AutoDock 4.2 have showed that indigocarpan possesses strong binding energy (ΔG) of - 7.68 kcal/mol towards MMP2 and - 6.35 kcal/mol towards MMP9, whereas batimastat showed binding energy (ΔG) of - 6.34 kcal/mol for MMP2 and - 5.66 kcal/mol for MMP9, meanwhile the results from AutoDock vina indicates that indigocarpan possesses strong binding energy (ΔG) of - 8.0 kcal/mol towards MMP2 and - 8.2 kcal/mol towards MMP9, whereas batimastat showed binding energy (ΔG) of - 7.2 kcal/mol for MMP2 and - 7.6 kcal/mol for MMP9. Also, the ADME and toxicity results suggest that the indigocarpan compound possesses a druggable pharmacokinetic potentiality and does not have carcinogenicity and Ames mutagenesis compared with other phytoligands. Hence, it is evident from our results that both AutoDock platforms strongly revealed that the phytoligand, indigocarpan possesses strong inhibitory activity against MMP2 and MMP9 to control cancer metastasis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02731-w. © King Abdulaziz City for Science and Technology 2021.