MOLECULAR DOCKING STUDIES ON THIADIAZOLE DERIVATIVES AS PROTEIN KINASE INHIBITORS
Objective: In the present study, a novel series of 1, 3, 4-thiadiazole derivatives were docked against the mycobacterium tuberculosis protein kinase G. 1, 3, 4â€“thiadiazole derivatives with a modified primary amine group at 5th position were used for docking studies.
Methods: The three-dimensional structure of the protein was obtained from PDB, and its active sites were predicted. The structures of all the compounds were drawn using chemdraw software version 8.0. The docking studies were done by using schrÃ¶dinger software against the enzyme protein kinase G. Totally eighteen compounds was synthesized based on glide score
Results: In this Docking study the thiadiazole analogues were showing good binding energy. The amino acids residues GLU588, SER412, GLY410 and GLU 628 in the kinase domain active site form hydrogen bonds with the ligand.
Conclusion: The compounds D34, D16, D7, D25, D15, and D27 showed better interaction with protein kinase G (pknG) more than the other drug molecules
2. Neetu Kumari T, Jaya Sivaswami T. Resazurin reduction assays for screening of anti-tubercular compounds against dormant and actively growing mycobacterium tuberculosis, mycobacterium bovis BCG and mycobacterium smegmatis. J Antimicrob Chemother 2007;60:288â€“93.
3. Ahmet Ilmaz Coban. A new rapid colorimetric method for testing Mycobacterium tuberculosis susceptibility to isoniazid and rifampicin: a crystal violet decolourisation assay. Mem Institute Oswaldo Cruz, Rio de Janeiro 2014;109:246-9.
4. Sunil S, Sachin Sharma, Sharma SK, Meharwal SK, Jindal SK, Meera Sharma. Drug susceptibility of Mycobacterium tuberculosis to primary antitubercular drugs by nitrate reductase assay. Indian J Med Res 2004;120:468â€“71.
5. Santhi N, Aiswarya S. Insights from the molecular docking of withanolide derivatives to the target protein PknG from Mycobacterium tuberculosis. Bioinformation 2011;7:1-5.
6. Borappa Muthukala, Kanakarajan Sivakumari, Kamalanathan Ashok. In silico docking of quercetin compound against the hela cell line proteins. Int J Curr Pharm Res 2015;7:13â€“6.
7. Vanitha Varadharaj, Naresh Kandakatla. Glycogen synthase kinase-3 beta protein inhibition by selected phytocompounds in silico. Asian J Pharm Clin Res 2017;10:87-90.
8. Smruthi G, Mahadevan V, Vadivel V, Brindha P. Docking studies on antidiabetic molecular targets of phytochemical compounds of syzygium cumini (l.) skeels. Asian J Pharm Clin Res 2016;9:287-93.