In Silico Insights into the Inhibitory Activity of Prodigiosin against Tumour Cells Targeting the Tyrosine Kinases Receptors

Prodigiosin (PDG) is a linear derivative of pyrrolyl dipyrromethene with a 4-methoxy,2-2-bi-pyrrole ring system. It is produced by some species of bacteria and eubacteria and is reputed for its anticancer activity against breast, colon and lung cancers via induced cellular stress. The study investigated the PDG binding interaction with several co-crystallized receptor tyrosine kinases (rTKs) to estimate the binding energies (E) and inhibition constants (Ki) of PDG. Prodigiosin was docked using AutoDock4.2 against 20 co-crystallized rTKs selected from the protein data bank, PDB. The E, Ki, RMSD, the number of H-bonds and the amino acids involved in the interactions of their best conformational poses were estimated and compared with those of doxorubicin, a potent cytotoxic agent. Comparatively, PDG interacted more efficiently with the collagen discoidin domain receptor subfamily 1 (DDR1) type II kinase protein (PDB: 4BKJ). A total of 16 amino acid residues were involved in hydrophobic (Val624, 2 Lys655, Glu672, Ile675, 2 Ile685, Met699, Thr701 and Asp784), hydrogen (2 Glu672, 3 Asp784) and π-stacking (Phe785) interactions with the DDR1 type II tyrosine kinase protein. A significant RMSD, E, Ki of 60.071 A, -10.04 Kcal/mol and 43.90 nM respectively for the binding of PDG to the rTK were obtained vis-a-viz native ligand, imatinib (78.961 A, -14.20 Kcal/mol and 39.11 ρM) and doxorubicin control (52.52 A, -8.65 Kcal/mol and 457.29 nM) respectively. The significantly higher inhibition of the DDR1 type II kinase protein by PDG compared with doxorubicin provides vital insights into understanding the molecular basis of the mechanism of anticancer activity and its clinical application in the treatment of breast, colon and lung cancers.