MOLECULAR DOCKING STUDIES OF HGV-6 ANALOGUE AS A POTENTIAL PBP-1A INHIBITOR
Objective: The sygnificance of this study is to find a new hexagamavunon-6 analogue (HGV-6); 3,5-bis-(4´-chlorobenzylidene)-tetrahydro-4H-thiopyran-4-one (D144); 3,5-bis-(2´,4´-dichlorobenzylidene)-tetrahydro-4H-thiopyran-4-one (D154); 3,5-bis-(3´,5´-dichlor ro-4´-hydroxybenzylidene)-tetrahydro-4H-thiopyran-4-one (D156) as a potential PBP-1A inhibitor.
Methods: Docking method through Molecular Operating Environment (MOE) software was used to design a new HGV-6 analogue and study its interaction with penicillin binding protein (PBP-1a). This docking study used parameterized model 3 (PM3) method through Polak Ribiere algorithm to calculate the optimal structural geometry of the compound. Protein validation was carried out to ensure that the protein was suitable for use.
Results: The results of the docking study show that the docking scores of D144 (-9.7942) and D154 (-10.1961) are higher than D156 (-12.2604), while D156 is lower than HGV-6 (-11.7958). Ampicillin (-13.6496) as a native ligand has the smallest docking score compared to the test compounds.
Conclusion: The results of the docking study show that 3,5-bis-(3,5-dichloro-4-hydroxybenzylidene)-tetrahydro-4H-thiopyran-4-one (D156) has a better potential antibacterial compound than HGV-6.
2. Eigner D, Scholz D. Ferula asa-foetida and curcuma longa in traditional medical treatment and diet in Nepal. J Ethnopharmacol 1999;67:1–6.
3. Liang G. Synthesis and anti-inflammatory activities of mono-carbonyl analogues of curcumin. Bioorg Med Chem Lett 2007;18:1525–9.
4. Kohli Ali J, Ansari Mj, Raheman Z. Curcumin: a natural antiinflammatory agent. Indian J Pharmacol 2005;37:141.
5. Gupta SC. Multitargeting by curcumin as revealed by molecular interaction studies. Nat Prod Rep 2011;28:1937.
6. Li S. Chemical composition and product quality control of turmeric curcuma longa L. Phythochem 2011;2:28-54.
7. Vijesh AM. Synthesis, characterization and antimicrobial studies of some new pyrazole incorporated imidazole derivatives. Eur J Med Chem 2011;46:3531–6.
8. Istyastono EP. Docking studies of curcumin as a potential lead compound to develop novel dipeptydyl peptidase-4 inhibitors. Indones J Chem 2010;9:132–6.
9. Yuniarti N. In vitro and in silico studies on curcumin and its analogues as dual inhibitors for cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). ITB J Sci 2012;44:51–66.
10. Lavanya P, Suresh M, Kotaiah Y, Harikrishna M, Rao CV. Synthesis, antibacterial, antifungal and antioxidant activity studies on 6-bromo-2-substitutedphenyl-1H-imidazo [4, 5-b] pyridine. Asian J Pharm Clin Res 2011;4:69–73.
11. Sun S, Selmer M, Andersson DI. Resistance to ?-lactam antibiotics conferred by point mutations in penicillin-binding proteins PBP3, PBP4 and PBP6 in salmonella enterica. Plos One 2014;9:97202.
12. Verdino A. Synthesis and biological evaluation of the progenitor of a new class of cephalosporin analogues, with a particular focus on structure-based computational analysis. Plos One 2017;12:0181563.
13. Pagadala NS, Syed K, Tuszynski J. Software for molecular docking: a review. Biophys Rev 2017;9:91–102,
14. Wijianto BR, Purnomo RH, Nurrochmad A. In silico and in vitro assay of HGV analogue as antibacterial. Int J Pharm Pharm Sci 2019;11:78–85.
15. Nicola G, Tomberg J, Pratt RF, Nicholas RA, Davies C. Crystal structures of covalent complexes of ?-lactam antibiotics with Escherichia coli penicillin-binding protein 5: toward an understanding of antibiotic specificity. Biochemistry 2010;49:8094–104.
16. Korb O, Stutzle T, Exner TE. Empirical scoring functions for advanced protein-ligand docking with plants. J Chem Inf Model 2018;49:84–96.
17. Syahri J, Yuanita E, Nurohmah BA, Armunanto R, Purwono B. Chalcone analogue as potent anti-malarial compounds against plasmodium falciparum: synthesis, biological evaluation, and docking simulation study. Asian Pac J Trop Biomed 2017;7:675–9.
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