Design, Molecular Docking, Synthesis and Biological Evaluation of 4, 5-Substituted 1, 2, 3-Triazoles as Anti-bacterial Agents
DOI:
https://doi.org/10.37285/ijpsn.2021.14.2.3Abstract
Newer antibacterial agents are needed to combat the growing bacterial infections. Triazoles are one of the leading and most sought out nucleus amongst the heterocyclic rings in the drug world. 1, 2, 3-Triazoles are synthesized by Click Chemistry of alkynes with azides. A synergistic effect is observed when the triazoles are combined with other heterocycles. They also exhibit diversified therapeutic activities like anti-viral, anti-bacterial, anti-diabetic, anti-tubercular, anti-inflam-matory, antihypertensive etc which makes Triazoles an interesting molecule for the researchers to work on. In the current study, we combined 1,2, 3-triazoles with thiophene ring system to get synergistic antibacterial activity. Here, 12 derivatives of 4, 5-substituted-1, 2, 3-Triazoles were subjected to in silico docking studies on Biotin ligase protein (PDB ID: 3V7R). The compounds that showed the best results were synthesized. The newly synthesized derivatives were characterized by using IR, H1 NMR and Mass spectrum. All the synthesized derivatives were evaluated for antibacterial activity against Gram-negative bacteria (E. coli and P. aerugenosa) and gram-positive bacteria (B. subtilis and S. aureus). The compounds showed moderate to good activity, which was comparable to that of the standard Streptomycin drug.
Downloads
Metrics
Keywords:
1, 2, 3-Triazoles, Docking, Molinspiration, Osiris, Click Chemistry, Antibacterial
Downloads
Published
How to Cite
Issue
Section
References
Abed ED and Mokhtaria B (2017). Synthesis and Antimicrobial Activity of some 1,4-Disubstitu- ted 1,2,3-Triazoles., Jour of App Chem, 10: 69-78.
Bhola Y, Naliapara A, Modi J and Naliapara Y (2019). Synthesis and biological activity of pyrazole and 1,2,3-triazole containing heterocyclic compounds., Wor Sci news 117: 29-43.
Biliavska L, Pankivska Y, Povnitsa O, Zagorodnya S, Gudz G and Shermolovich Y (2018). Anti-Adenoviral Activity of 2-(3-Chlorotetrahydrofuran-2-yl)-4-Tosyl-5-(Perfluoropropyl)-1,2,3-Triazole., Med Jour 56: 871-882
Bola Y, Naliapara A and Para J (2019). Synthesis and Biological activity of Pyrazole and 1, 2, 3-Triazole containing heterocyclic compounds, Jour of Med Chem 23: 2392-2401.
Chavan PV, Desai UV, Wadgaonkar PP, Tapase SR, Kodam KM, Choudhari A and Sarkar D (2019) Click chemistry based multicomponent approach in the synthesis of spirochro-menocarbazole tethered 1,2,3-triazoles as potential anticancer agents., Jour of Bio Chem28: 3012-3022.
Dongamandi A, Rangu K, Gundu S and Velagapuri HR (2017). Microwave Assisted Synthesis of new Pyrazole derivatives, Consisting of 1, 2, 3-Triazole scaffold as potential antimicrobial agents., Jour of Ser Chem Soc 82: 357-366.
Erazua EA, Oyebamiji AK and Adeleke BB (2018). DFT-QSAR and Molecular Docking Studies on 1,2,3-Triazole-Dithiocarbamate Hybrids as Potential Anticancer Agents., Phys Sci Int Jour 24: 1-10.
Ewing TJA, Makino S, Skillman AG and Kuntz ID (2001). DOCK 4.0: Search strategies for automated molecular docking of flexible molecule databases. Jour of Com.-Aid MolDesc 15: 411−428.
Feng J, Paparella AS, Booker GW and Polyak SW (2016). A DAbell- Biotin Protein Ligase Is a Target for New Antibacterials, Anti 56: 22-33.
Govindaiiah S, Srinivasa S, Ramakrishna RA, Rao TMC and Nagabhushana H (2018) Regioselective synthesis, antibacterial and molecular docking studies of 1-Benzhydryl piperazine derived 1, 4-substituted-1, 2, 3-triazoles, Chem Sel 3: 8111-8117.
Hein C D, Luing X M and Wang D (2008). Click Chemistry a Powerful tool in Pharmaceutical Chemistry., HHS Publications 25: 2216-2230.
Huo J, Hu H, Zhang M, Hu X, Chen M,Chen D, Liu J, Xiao G, Wanga Y and Wena Z (2017). A mini review of the synthesis of poly-1,2,3- triazole-based functional materials., Roy Soc of Chem 7: 2281-2290.
Gan LL, Zhang HZ and Zhou CH (2018). Design, Synthesis and Relational Biological Evaluation of Novel Diphenylpiperazine 1,2,3-triazole Derivatives., Jour of Med Chem 82: 223-233.
Jadhav RP, Raundal HN, Patil AA and Bobade VD (2015). Synthesis and biological evaluation of a series of 1,4-disubstituted 1,2,3-triazole derivatives as possible antimicrobial agents., Jour of Sau Ar Soc of Chem 45: 152-159.
Klebe G (2006). Virtual ligand screening: strategies, perspectives and limitations. Drug Disc Tod 11: 580−594.
Kumar S, Saha ST, Gu L, Palma G, Perumal S, Pillay AS, Singh P, Anand A, Kaur M and Kumar V(2018). 1H-1,2,3-Triazole Tethered Nitroimidazole−Isatin Conjugates: Synthesis, Docking and Anti Proliferative evaluation of Breast Cancer., ACS Om 3: 12106−12113.
Kumari R and Subramaniyan M R (2010). Synthesis and Biological evolution of 1, 2, 3-Triazoles., Jour of Org Chem 67: 54-56.
Kumar SV, Scottwell S, Waugh E, McAdam CJ, Hanton LR, Brooks HJL and Crowley JD (2016). Antimicrobial Properties of Tris(homoleptic) Ruthenium(II) 2-Pyridyl-1,2,3-triazole “Click” Complexes against Pathogenic Bacteria, Including Methicillin-Resistant Staphylococcus aureus (MRSA)., Jour of Inorg Chem 15: 74-80.
Mokhtaria B and Douniazadia EA (2017). Synthesis and Antimicrobial Activity of some 1,4-Disubstituted 1,2,3-Triazoles., Int Jour of App Chem 10: 69-78.
Nadathur P (2007). An Introduction to Homology, Jour of Eng and Tech 88: 7761-7771.
Nalawade J, Shinde A, Chavan A, Patil S and Suryavanshi M (2019). Synthesis of new thiazolyl-pyrazolyl-1,2,3-triazole derivatives as potential antimicrobial agents., Eur Jour of Med Chem 82: 2201-2213.
Nylund K, Johansson P, Puterowa Z, Krutosikova A, Zurabishvii D and Samsonia Sh. A (2010). Heterocyclic compounds: Synthesis, Properties and applications., Chem ResApp Ser 18: 403.
Organic Chemistry Portal, OSIRIS. [internet] Available from: https://www.organic-chemistry.org/prog/peo/
Presolski S I, Hong VP and Phinn M. G (2010). Copper Catalyzed Azide Alkyne Click Reaction. Scri Res Inst 44: 6745-6751.
Potts K.T (2006). The Chemistry of 1, 2, 4-Triazoles,Chem Rev 9: 53-61.
Prakash CK, Kumar K, Kumar D, Mor S, Kumar A and Jindal DK (2017). Regioselective synthesis, characterization and anti-microbial evaluation of amide–ether-linked 1,4-disubstituted 1,2,3-triazoles., Jour of the Sib Chem Soc 82: 995-1007.
Radhi AH and Himasree Y (2016). Synthesis and Biological activity of 1, 2, 3-Triazolyl coumarins., Jour of Chem and Pharm Res 18: 823-833.
Ruddarraju PR, Murugulla AC, Kotla R, Tirumalasetty MCB, Wudayagiri R, Donthabakthuni S and Marojuc R (2016). Design, synthesis, anticancer activity and docking studies of theophylline containing 1,2,3-triazoles with variant amide derivatives, Med Chem let 163: 1-3.
Singh S, Gupta A K and Verma A (2013) Molecular Properties and Bioactivity score of the Aloe veraantioxidant compounds – in order to lead finding. Res Jour of Pharm, Biol and Chem Sci 4: 876.
Sunitha V, Kumar KA, Krishna TM and Ramesh M (2016). Synthesis, Molecular evaluation and docking studies of novel 1, 2, 3-triazole derivatives as potent anti-inflammatory agents, Russ Jour of Gen Chem 124: 1154-1162.
Totobenzara J and Burke A J (2015). New Click Chemistry methods for 1, 2, 3-Triazoles synthesis: recent advances and applications, Tetrlet 56: 2853-2859.
Totrov M and Abagyan R (2008). Flexible ligand docking to multiple receptor conformations: a practical alternative., CurrOpi in Struc Bio 18: 178–184.
Vu LA, Quyen PT and Huong NT (2015). In silico Drug Design: Prospective for Drug Lead Discovery., Int Jour of Eng Sci Inv., 7: 55-59.
Zhang SY, Fu DJ, Yue XX, Liu YC, Song J, Sun HH, Liu HM and Zhang YB (2016). Design, Synthesis and Structure-Activity Relationships of Novel Chalcone-1,2,3-triazole-azole Derivates as Antiproliferative Agents., Mol 23: 122-134.
