Abstract

INHIBITION OF MYCOBACTERIUM TUBERCULOSIS PROTEIN KINASE B BY IN-SILICO DRUG DESIGNING OF NEW POTENT INHIBITORS INDICINE N-OXIDE, LYCOPSAMINE AND SUPININE

S. Pooja Sri* and S. Sribal

ABSTRACT

The main aim of this research paper is to cure the disease tuberculosis in human by introducing a new generic medicated drug with low cost effective. This hypothesis is based on the inhibition of Mycobacterium tuberculosis protein kinase B which changing the other proteins by adding a phosphate groups to them by a process called phosphorylation. And it often usually results in a functional group change of the target protein, cellular location, association with other proteins. From the previous research studies it’s found that the protein kinase B expression is necessary for cell survival with depletion orover expression of pKnB gene leading to cell death. Protein kinase B is not only necessary for the growth of the pathogen in vitro but is also essential for the survival of the pathogen in the host system (Homo sapiens). In this research work 14 phytoligands were selected which is found in the medicinal plant Heliotropium indicum, they are heliotrine, helindicine, lycopsamine, indicine, indicine N-oxide, heleurine, supinine, supinidine, lindelofidine, trachelanthamidine, retronecine, putrescine, spermidine, spermine. The docking of protein kinase B is done with each designed 14 ligand molecules by using Autodock vina software. By evaluating the RMSD table value, the minimum binding energy of the lead compound is identified. From the RMSD values, the phytoligands lycopsamine (-9.19), Indicine N-oxide (-10.17) and supinine (-9.14) shows the minimum binding energy with the protein kinase B active site of amino acid Valine residue 95. The protein-phytoligand complex is visualized using a molecular visualizing software UCSF chimera to study the interaction between phytoligands and protein. The predicted ADMET result shows that the phytoligands lycopsamine, Indicine N-oxide and supinine having the potent property against the dreadful disease tuberculosis. From this computational biology study it has been proved that the phytoligand molecules lycopsamine, indicine N-oxide and supinine have the ability to kill the Mycobacterium tuberculosis H37RV by inhibiting the expression of protein kinase B.

Keywords: pKnB, mycobacterium tuberculosis H37RV, heliotrine, helindicine, lycopsamine, indicine, indicine N-oxide, heleurine, supinine, supinidine, lindelofidine, trachelanthamidine, retronecine, putrescine, spermidine, spermine, Autodock vina, RMSD value, active