Molecular Docking and Pharmacokinetic Studies of Some New pyridyl and hydrazinyl bearing thiazole Derivatives as Potential DNA gyrase Inhibitors
Abstract
An essential bacterial protein called DNA gyrase is involved in transcription and replication and stimulates the negative super-coiling of the circular DNA found in bacteria. Since its inhibition causes bacterial mortality, DNA gyrase is a well-known target for antibacterial drugs. Gyrase is inhibited by quinolones, coumarins, and cyclothialidines. The objective of the present study is to evaluate the binding interaction of pyridyl and hydrazinyl-bearing thiazole compounds with DNA gyrase inhibitors and also check the ADME properties of all compounds. We performed docking and pharmacokinetic studies of 28 novel hypothetical compounds. Interacting amino acids of receptor DNA gyrase with reference drug prothionamide were VAL 167, VAL 71, ILE 78, and THR 165 and binding affinity was found to be -5.61 kcal/mol. Most of our docked compounds also show interaction with amino acids VAL 71 and ILE 78 with superior binding affinity. Molecular docking suggests that all the synthesized derivatives have shown higher level binding affinity in contrast to standard drug prothionamide and have an acceptable range of ADME properties.
Keywords:
Antimicrobial, Docking, DNA gyrase, Swiss-ADME, Skin permeabilityDOI
https://doi.org/10.25004/IJPSDR.2022.140624References
Patrizio P, Francesca P, Annalisa P. Antimicrobial resistance: a global multifaceted phenomenon. Pathog Glob Health. 2015; 109:309–318. dOI: 10.1179/2047773215Y.0000000030
Makam P, Kannan T. 2-Aminothiazole der ivat ives as antimycobacterial agents: Synthesis, characterization, in vitro and in silico studies. Eur J Med Chem. 2014; 87:643-656. doi: 10.1016/j. ejmech.2014.09.086
Helal MH, Salem MA, El-Gaby MS, Aljahdali M. Synthesis and biological evaluation of some novel thiazole compounds as potential anti-inflammatory agents. Eur J Med Chem. 2013; 65:517-526. doi: 10.1016/j.ejmech.2013.04.005
Chaubey A, Pandeya SN. Pyridine a versat ile nucleus in pharmaceutical field. Asian J Pharm Clin Res. 2011; 4:5-8.
Sahoo CR, Patro R, Sahoo J, Padhy RN, Paidesetty SK. Design, Molecular Docking of Synthesized Sciff-Based Thiazole/Pyridine Derivatives as Potent Antibacterial Inhibitor. IDMA 2019; 56:20-25.
Sahoo CR, Paidesetty SK, Padhy RN. Norharmane as a potential chemical entity for development of anticancer drugs, Eur J Med Chem. 2019; 162:752-764. doi: 10.1016/j.ejmech.2018.11.024
Sahoo CR, Paidesetty SK, Padhy RN. Nornostocine congeners as potential anticancer drugs: An overview. Drug Dev Res. 2019; 80:878-892. https://doi.org/10.1002/ddr.21577
Mishra I, Chandra P, Mishra R, Mujwar S, Sachan N. A retrospect on antimicrobial potential of thiazole scaffolds. J Heterocycl Chem. 2020; 57:2304–2329. https://doi.org/10.1002/jhet.3970
Meleddu R, Corona A, Distinto S. Exploring the thiazole scaffold for the identification of new agents for the treatment of fluconazole resistant Candida. J. Enzyme Inhib Med Chem. 2016; 3:1672–1677. doi: 10.3109/14756366.2015.1113171.
Singh I, Gupta S, Kumar S. Thiazole Compounds as Antiviral Agents: An Update. Med Chem 2020; 16:4–23 10.2174/157340641566619 0614101253.
Abu-Melha S, Abdelaziz MR, Mastoura ME, Sayed MR, Mohamad R, Abdo AE, Sobhi MG. Clean grinding technique: A facile synthesis and in silico antiviral activity of hydrazones, pyrazoles, and pyrazines bearing thiazole moiety against SARS-CoV-2 main protease. MDPI. 2020; 25:45-65. doi: 10.3390/molecules25194565
Gomha S, Altalbawy F, Edrees M. Synthesis and Characterization of Some New Bis-Pyrazolyl-Thiazoles Incorporating the Thiophene Moiety as Potent Anti-Tumor Agents. Int J Mol Sci. 2016; 17:1499. doi: 10.3390/ijms17091499
da Silva EB, da Silva Mendes CH, silva O, Fereira RS, Leite ACL. Desing and synthesis of potent anti-Trypanosoma cruzi agents new thiazoles derivatives which induce apoptotic parasite death. Eur J Med Chem. 2017; 130:39–50. https://doi.org/10.1016/j. ejmech.2017.02.026
Woods KW, Bell RL, McCroskey RW, Michaelides MR, Wada CK, Hulukower KI. Thiazole analogues of the NSAID indomethacin as selective COX-2 Inhibitors. Bioorg Med Chem Lett. 2001; 11:1325– 1328. doi: 10.1016/s0960-894x(01)00212-8.
Araniciu C, Benedec D, Parvu AE, Palage MD, Oniga SD, Oniga L, Oniga O. The Effect of Some 4, 2 and 5, 2 Bis-thiazole Derivatives on Nitro-Oxidative Stress and Phagocytosis in Acute Experimental Inflammation. MDIP. 2014; 19:9240-9256. https://doi.org/10.3390/ molecules19079240
Liaras K, Fesatidou M, Geronikaki A. Thiazoles and Thiazolidinones as COX/LOX Inhibitors. MDIP 2018; 23:685-688. doi: 10.3390/ molecules23030685.
Abdel A, Camel M. Synthesis of new thiazolo-celecoxib analogues as dual cyclooxygenase-2/15-lipoxygenase inhibitors: Determination of regio-specific different pyrazole cyclization by 2D NMR. Eur J Med Chem. 2016; 26:2893–2899.
Reece RJ, Maxwell A. DNA Gyrase: Structure and Function .Crit. Rev. Biochem 2008; 26:335-375. doi: 10.3109/10409239109114072.
Wang JC DNA TOPOISOMERASES. Annu Rev Biochem. 1996; 65:635- 692. doi: 10.1146/annurev.bi.65.070196.003223.
Ali JA, Howells AJ, Jackson AP, Maxwel A. The 43-kilodalton N-terminal fragment of the DNA gyrase B protein hydrolyzes ATP and binds coumarin drug. B biochem 1993; 32:2717-2724. doi: 10.1021/bi00061a033.
Maxwell A, Ali JA, Jackson AP, Howells AJ, Maxwel A. Nucleotide binding to the 43-kilodalton N-terminal fragment of the DNA gyrase B protein. B biochem 1995; 34:9801-9808. doi: 10.1021/ bi00061a033.
Rizk EK, Ibrahim AMR. Design, synthesis and docking studies of novel thiazole derivatives incorporating pyridine moiety and assessment as antimicrobial agents. Sci Rep. 2021; 11:7846. doi: 10.1038/s41598-021-86424-7.
Shen LL, Chu DTW. Type II DNA topoisomerases as antibacterial targets. Curr Pharm Des. 1996; 2:195-208. doi: 10.1007/978-1- 4939-7459-7_3
Engle EC, Drlica K, Manes SH. Differential effects of antibiotics inhibiting gyrase. J Bacteriol. 1982; 149:92–98. doi: 10.1128/ jb.149.1.92-98.1982.
Daina A, Zoete V. A boiled‐egg to predict gastrointestinal absorption and brain penetration of small molecules. Chem Med Chem. 2016; 11:1117–1121. https://doi.org/10.1002/cmdc.201600182
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