V. Vijayakumar, N. Radhakrishnan, P. Vasantha-Srinivasan
V. Vijayakumar1, N. Radhakrishnan2*, P. Vasantha-Srinivasan3
1Department of Chemistry, Anna University, Chennai-25, Tamil Nadu, India.
2,3Department of Biochemistry, St. Peter’s Institute Higher Education and Research, Avadi, Chennai, Tamil Nadu, India.
Volume - 13,
Issue - 6,
Year - 2020
Triazole analogues are well known to have desirable properties for medicinal chemistry such as hydrogen bonding capability, moderate dipole character, rigidity and stability under in vivo conditions etc. This prompts us to carry out the present study, we have selected 20 triazole analogues and evaluated on the docking behavior of four targeted enzymes such as HNE, MMP 2, MMP 9 and tyrosinase. The molecular physicochemical analysis revealed that all the tested ligands (expect ligand 5 and 18) showed nil violation and complied well with the Lipinski’s rule of five. ADME analysis showed that ligand 15 alone predicated to have low gastrointestinal (GI) absorption effect. Docking studies revealed that ligand 18 [2-(2,4-difluorophenyl)-1-(4-((1-(4-ethylbenzyl)-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ol] had exhibited the maximum binding energy for three target enzymes such as HNE, MMP 2 and MMP 9. The present study has paved a new insight in understanding 20 triazole analogues as potential inhibitors against HNE, MMP 2, MMP 9 and tyrosinase.
Cite this article:
V. Vijayakumar, N. Radhakrishnan, P. Vasantha-Srinivasan. Molecular Docking Analysis of Triazole Analogues as Inhibitors of Human Neutrophil Elastase (HNE), Matrix Metalloproteinase (MMP 2 and MMP 9) and Tyrosinase. Research J. Pharm. and Tech 2020; 13(6): 2777-2783. doi: 10.5958/0974-360X.2020.00493.X
V. Vijayakumar, N. Radhakrishnan, P. Vasantha-Srinivasan. Molecular Docking Analysis of Triazole Analogues as Inhibitors of Human Neutrophil Elastase (HNE), Matrix Metalloproteinase (MMP 2 and MMP 9) and Tyrosinase. Research J. Pharm. and Tech 2020; 13(6): 2777-2783. doi: 10.5958/0974-360X.2020.00493.X Available on: https://rjptonline.org/AbstractView.aspx?PID=2020-13-6-43
1. Asif M. A brief review on anti-tubercular activity of pharmacological activity of some triazole analogues. Global J Res and Rev. 2014; 1(3):051-058.
2. Otuokere IE, Amaku FJ, Alisa CO. In silico geometry optimization, excited – state properties of (2E)-N-Hydroxy-3-[3-(Phenylsulfamoyl) Phenyl] prop-2-enamide (Belinostat) and its molecular docking studies with Ebola Virus glycoprotein. J Pharm Res 2015; 5(3):131-137.
3. Sudhakar P, Pushkalai S, Poorana, Sabarinath C, Priyadharshini S, Haripriya S. Molecular docking and synthesis of 1, 2, 4 -triazin analogue of diclofenac as potential ligand for parkinson's. Res J Pharm Pharmcodynamics 2018; 10(1):8-12.
4. Panigrahi N, Ganguly S, Jagadeesh P. Synthesis, antimicrobial evaluation and molecular docking studies of novel Oxazolidinone-thiophene chalcone hybrid derivatives. A J Res and Tech 2018; 11(12):5611-5622.
5. Chellamalla R, Makula A. Molecular docking studies and ADMET predictions of pyrimidine coumarin scaffolds as potential IDO inhibitors. A J Res Chem 2017; 10(3):331-340.
6. Hasan T, Ghalib RM, Mehdi SH, Singh PK, Baqri SSR. Normal mode analysis, electronic parameters and molecular docking study of 3, 5, 4’-Trihydroxy-6, 7-dimethoxy-flavone (Eupalitin) using first principle. A J Res Chem 2017; 10(6):789-797.
7. Ramjith US, Shahim M. Molecular docking study of novel imidazo-1, 3, 4 thiadiazole derivatives. Res J Pharm and Tech 2013; 6(6):688-694.
8. Pavlo V, Zadorozhnii VV, Kiselev, AE, Titova, AV, Kharchenko, Ihor O. Pokotylo OV, Okhtina. Molecular docking studies of N-5-aryl-1, 3, 4-oxadiazolo-2, 2-dichloroacet-amidines as inhibitors of enoyl-ACP reductase Mycobacterium tuberculosis. Res J Pharm and Tech 2017; 10(4):1091-1097.
9. Pavlo VZadorozhnii, Vadym VK, Nataliia OT, Aleksandr VK, Ihor OP, Oxana VO, Oxana VK. In Silico prediction and molecular docking studies of N-Amidoalkylated derivatives of 1, 3, 4-oxadiazole as COX-1 and COX-2 potential inhibitors. Res J Pharm and Tech 2017; 10(11):3957-3963.
10. Godhani DR, Jogel AA, Sanghani AM, Mehta JP. Synthesis and biological screening of 1, 2, 4-triazole derivatives. Ind J Chem. 2015; 54B:556-564.
11. Kumar H, Javed SA, Khan SA, Amir M. 1, 3, 4-Oxadiazole/thiazole and 1,2,4-triazole derivatives of biphenyl-4-yloxy acetic acid: Synthesis and preliminary evaluation of biological properties. Euro J Med Chem. 2008; 43:2688-2698.
12. Wuest F, Tang X, Kniess T, Pietzsch J, Suresh M. Synthesis and cyclooxygenase inhibition of various (aryl-1,2,3-triazole-1-yl)-methanesulfonylphenyl derivatives. Bio Med Chem. 2009; 17:1146-1151.
13. Vijayakumar V, Radhakrishnan N, Rameshkumar C. Molecular docking analysis of imidazole derivatives and polybenzimidazole analogues as inhibitors of superoxide dismutase (SOD) and Xanthine oxidase (XO). IEEE International Conference on Smart Technologies and Management for Computing, Communication, Controls, Energy and Materials (ICSTM) 2017; 513-516.
14. Navjot Kaur, Monika, Kulwinder Singh. 3D-QSAR and Molecular Docking Studies of N-(2-Aminophenyl)-Benzamide Derivatives as Inhibitors of HDAC2. Res J Pharm and Tech 2014; 7(7):760-770.
15. Wang J, Urban L. The impact of early ADME profiling on drug discovery and development strategy. Drug Discovery World. 2004; 5:73-96.
16. Hailu M, Narayanaswamy R, Abrehame S, Manoj VR. In silico analysis of Glycogen Synthase Kinase 3-Beta (GSK-3β) as aflatoxin binder. Biomed Pharmacol J 2019; 12(3):1449-1456.
17. Lipinski CA, Lambardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001; 46:3-26.
18. Singh S, Gupta AK, Verma A. Molecular properties and bioactivity score of the Aloe vera antioxidant compounds- In order to lead finding. Res J Pharm Biol Chem Sci. 2013; 4(2):876-891.
19. Vijayakumar V, Radhakrishnan N, Rameshkumar C. Predicting the biodegradability nature of imidazole and its derivatives by modelling two histidine degradation enzyme (Urocanase and Formiminoglutamase) activities. Asian J Pharm Clin Res. 2017; 10 (11):383-386.
20. Wang J, Urban L. The impact of early ADME profiling on drug discovery and development strategy. Drug Discovery World. 2003; 5:73-96.
21. Radhakrishnan N, Lam KW, Intan IS. In silico analysis of selected honey constituents as human neutrophil elastase (HNE) and matrix metalloproteinases (MMP 2 and 9) inhibitors. Int J Food Prop. 2015; 18:2155-2164.
22. Radhakrishnan N, Lam KW, Faridah A, Intan IS. Molecular docking analysis of curcumin analogues elastase (HNE) inhibitors. Bangladesh J. Pharmacol. 2014; 9:77-82.
23. Radhakrishnan N, Lam Kok Wai, Norhaizan Mohd Esa. Molecular docking analysis of phytic acid and 4-hydroxyisoleucins as cyclooxygenase-2, microsomal prostaglandin E synthase-2, tyrosinase, human neutrophil elastase, matrix metalloproteinase-2 and 9, xanthine oxidase, squalene synthase, nitric oxide synthase, human aldose reductase and lipoxygenase inhibitors. Pharmacogn Mag. 2017; 13 (51):S512-S518.
24. Vijayakumar V, Prabakaran A, Radhakrishnan N, Muthu S, Rameshkumar C, Paulraj EI. Synthesis, characterization, spectroscopic studies, DFT and molecular docking analysis of N4, N4′-dibutyl-3, 3′-diaminobenzidine. J Mol Struct. 2019; 1179:325-335.
25. Gumrukcuoglu N, Sokmen BB, Ugras S, Ugras HI, Yanardag R. Synthesis, antibacterial, antielastase, antiurease and antioxidane activities of new 1,4-butylene bridged bis-1,2,4-triazole derivatives. J Enzyme Inhib Med Chem. 2013; 28(1):89-94.
26. Vergelli C, Schepetkin IA, Crocetti L, Lacovone A, Giovannoni MP, Guerrini G, Khlebnikov AI, Ciattini S, Ciciani G, Quinn MT. Isoxazol-5(2H)-one: a new scafford for potent heman neutrophil elastase (HNE) inhibitors. J Enzyme Inhib Med Chem. 2017; 32(1):821-831.
27. Romanchikova N, Trapencieris P, Zemitis J, Turks M. A new matrix metalloproteinase-2 inhibitor triazolylmethyl aziridine reduces melanoma cell invasion, angiogenesis and tergets ERK1/2 phosphorylation. J Enzyme Inhib Med Chem. 2014; 29(6):765-772.
28. Testero SA, Llarrull LI, Fisher JF, Chang M, Mobashey S. Exploring the functional space of thiiranes as gelatinase inhibitors using click chemistry. ARKIVOC 2011; 7:221-236.
29. Akdogan ED, Erman B, Yelekci K. In silico design of novel and highly selective lysine specific histone demethylase inhibitors. Turk J Chem. 2011; 35:523 42.
30. Unver Y, Celik F, Dugdu E, Barut B, Sancak K. Synthesis of new bis-triazole compounds including Schiff bases and enzyme inhibition and antioxidant activities. J Med Chem. 2016; 1(1): 005-010.
31. Rafiq M, Saleem M, Hanif M, Kang SK, Seo SY, Lee KH. Synthesis, structural elucidation and bioevaluation of 4-amino-1, 2, 4-triazole-3-thione’s Schiff base derivatives. Arch Pharm Res. 2015.