Design, Synthesis, Molecular Docking and In silico Analysis of Some Novel 2-Amino-1, 3, 4-Thiadiazole Derivatives as Potent DNA Gyrase B Inhibitors

Author(s): Natarajan Ramalakshmi*, Prabakaran A., Sumithra S., Keerthika S., Nivetha J., Raveena R.

Journal Name: Current Bioactive Compounds

Volume 17 , Issue 7 , 2021


Article ID: e010621188864
Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Introduction: Thiadiazole derivatives have been reported as a potent antimicrobial agent and the discovery of drug molecules for antimicrobial-resistant strains of Escherichia coli is still a vital challenge in the modern world.

Objective: The objective of the present study is to design, synthesize and perform molecular docking studies and in-silico analysis of some novel 2-amino-1, 3, 4-thiadiazole derivatives with the aim of developing potential DNA gyrase B inhibitors.

Materials and Methods: The compound 5-substituted-1, 3,4-thiadiazol-2-amine derivatives [compound 1a-1c] ; 5,6-Diphenyl- 2-{[5-(substituted)-1,3,4-thiadiazol-2-yl amino]}-2H -1,2,4-triazine- 3-thione derivatives [compound 2a-2c]; and propyl 3,4,5-trihydroxy-2,6-bis {[5-(substituted)- 1,3,4-thiadiazol-2-yl amino] benzoate derivatives [compound 3a -3c] were synthesised by temperature- controlled microwave-assisted method. The structures of the synthesized compounds were drawn in ChemSketch. Further, molecular docking and in-silico studies for the prediction of druglikeness, pharmacokinetic parameters and prediction of toxicity were carried out . The structures of the synthesized compounds were characterized by FT-IR, 1H NMR and mass spectral analysis.

Results: The synthesized compounds had a better yield.The docking studies of the synthesized compounds had a better docking score with a good binding affinity towards the protein molecule. The synthesized compounds also comply with the in-silico prediction of drug-likeness, pharmacokinetic parameters and prediction of toxicity.

Conclusion: The present study reveals that the 5-substituted-1, 3,4-thiadiazol-2-amine derivatives can serve as a better lead as potent DNA gyrase B inhibitor in further drug discovery.

Keywords: 2-amino-1, 3, 4-thiadiazole derivatives, microwave-assisted synthesis, molecular docking, DNA gyrase B inhibitor, in-silico analysis, drug discovery.

[1]
World Health Organization. Antimicrobial resistance Weekly Epidemiological Record= Relevé épidémiologique hebdomadaire 75(41): 336-6.
[2]
Holmes AH, Moore LS, Sundsfjord A, et al. Understanding the mechanisms and drivers of antimicrobial resistance. Lancet 2016; 387(10014): 176-87.
[http://dx.doi.org/10.1016/S0140-6736(15)00473-0] [PMID: 26603922]
[3]
Sayah RS, Kaneene JB, Johnson Y, Miller R. Patterns of antimicrobial resistance observed in Escherichia coli isolates obtained from domestic- and wild-animal fecal samples, human septage, and surface water. Appl Environ Microbiol 2005; 71(3): 1394-404.
[http://dx.doi.org/10.1128/AEM.71.3.1394-1404.2005] [PMID: 15746342]
[4]
Chisholm SA, Unemo M, Quaye N, et al. Molecular epidemiological typing within the european gonococcal antimicrobial resistance surveillance programme reveals predominance of a multidrug-resistant clone. Euro Surveill 2013; 18(3): 20358.
[PMID: 23351652]
[5]
von Baum H, Marre R. Antimicrobial resistance of Escherichia coli and therapeutic implications. Int J Med Microbiol 2005; 295(6-7): 503-11.
[http://dx.doi.org/10.1016/j.ijmm.2005.07.002] [PMID: 16238024]
[6]
Spratt BG. Escherichia coli resistance to β-lactam antibiotics through a decrease in the affinity of a target for lethality. Nature 1978; 274(5672): 713-5.
[http://dx.doi.org/10.1038/274713a0] [PMID: 209344]
[7]
Tenover FC. Mechanisms of antimicrobial resistance in bacteria. Am J Med 2006; 119(6)(Suppl. 1): S3-S10.
[http://dx.doi.org/10.1016/j.amjmed.2006.03.011] [PMID: 16735149]
[8]
Zankari E, Hasman H, Cosentino S, et al. Identification of acquired antimicrobial resistance genes J Anti micro Chemo 2012; 67(11): 2640-4.
[9]
Poirel L, Madec JY, Lupo A, et al. Antimicrobial resistance in Escherichia coli. Antimicrobial Resistance in Bacteria from Livestock and Companion Animals 2018; pp. 289-316.
[10]
Erb A, Stürmer T, Marre R, Brenner H. Prevalence of antibiotic resistance in Escherichia coli: overview of geographical, temporal, and methodological variations. Eur J Clin Microbiol Infect Dis 2007; 26(2): 83-90.
[http://dx.doi.org/10.1007/s10096-006-0248-2] [PMID: 17235554]
[11]
Mishra G, Singh AK, Jyoti K. Review article on 1, 3, 4-thiadiazole derivatives and its pharmacological activities. Int J Chemtech Res 2011; 3: 1380-93.
[12]
Patel RV, Kumari P, Rajani DP, Pannecouque C, De Clercq E, Chikhalia KH. Antimicrobial, anti-TB, anticancer and anti-HIV evaluation of new s-triazine-based heterocycles. Future Med Chem 2012; 4(9): 1053-65.
[http://dx.doi.org/10.4155/fmc.12.57] [PMID: 22709250]
[13]
Chung KT, Jr SS, Lin WF, Wei CI. Growth inhibition of selected food‐borne bacteria by tannic acid, propyl gallate and related compounds. Lett Appl Microbiol 1993; 17(1): 29-32.
[http://dx.doi.org/10.1111/j.1472-765X.1993.tb01428.x]
[14]
Jadhav SA, Pardeshi RK, Shioorkar MG, Chavan OS, Vaidya SR. Comparative study of one pot synthetic methods of 2-amino-1, 3, 4-thiadiazole. Synthesis 2015; 1022: 621.
[15]
Soliman FS, Labouta IM, El Sebai AI, El Dine SS. Synthesis of 5, 6-Diaryl-1, 2, 4-triazines. Z Naturforsch B 1978; 33(12): 1503-7.
[http://dx.doi.org/10.1515/znb-1978-1228]
[16]
Roman G. n-Propyl gallate as substrate in the Mannich reaction. Proc Rom Acad B 2016; 18(3): 175-80.
[17]
Islam MA, Pillay TS. Identification of promising anti-DNA gyrase antibacterial compounds using de novo design, molecular docking and molecular dynamics studies. J Biomol Struct Dyn 2020; 38(6): 1798-809.
[PMID: 31084271]
[18]
Udugade SBC, Doijad R, Udugade BV. In silico evaluation of pharmacokinetics, drug-likeness and medicinal chemistry friendliness of momordicin1: an active chemical constituent of Momordica charantia. J Adv Sci Res 2019; 10(3)
[19]
Jarrahpour A, Fathi J, Mimouni M, et al. Petra, Osiris and Molinspiration (POM) together as a successful support in drug design: antibacterial activity and biopharmaceutical characterization of some azo Schiff bases. Med Chem Res 2012; 21(8): 1984-90.
[http://dx.doi.org/10.1007/s00044-011-9723-0]
[20]
Durojaye O A. International Jour Pharmaceu 2018.
[21]
Rocha JA, Rego NCS, Carvalho BTS, et al. Computational quantum chemistry, molecular docking, and ADMET predictions of imidazole alkaloids of Pilocarpus microphyllus with schistosomicidal properties. PLoS One 2018; 13(6)
[http://dx.doi.org/10.1371/journal.pone.0198476] [PMID: 29944674]
[22]
Banerjee P, Eckert AO, Schrey AK, Preissner R. ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res 2018; 46(W1): W257-63.
[http://dx.doi.org/10.1093/nar/gky318] [PMID: 29718510]
[23]
Ali TE, Abdel-Rahman RM, Hanafy FI, El-Edfawy SM. Synthesis and molluscicidal activity of phosphorus-containing heterocyclic compounds derived from 5, 6-bis (4-bromophenyl)-3-hydrazino-1, 2, 4-triazine. Phosphorus Sulfur Silicon Relat Elem 2008; 183(10): 2565-77.
[http://dx.doi.org/10.1080/10426500801967864]
[24]
Medina ME, Iuga C, Alvarez-Idaboy JR. Antioxidant activity of propyl gallate in aqueous and lipid media: a theoretical study. Phys Chem Chem Phys 2013; 15(31): 13137-46.
[http://dx.doi.org/10.1039/c3cp51644j] [PMID: 23824251]
[25]
Rzeski W, Matysiak J, Kandefer-Szerszeń M. Anticancer, neuroprotective activities and computational studies of 2-amino-1,3,4-thiadiazole based compound. Bioorg Med Chem 2007; 15(9): 3201-7.
[http://dx.doi.org/10.1016/j.bmc.2007.02.041] [PMID: 17350846]
[26]
Serban G, Stanasel O, Serban E, Bota S. 2-Amino-1,3,4-thiadiazole as a potential scaffold for promising antimicrobial agents. Drug Des Devel Ther 2018; 12: 1545-66.
[http://dx.doi.org/10.2147/DDDT.S155958] [PMID: 29910602]
[27]
Chaudhary DK, Chaudhary RP. Pharmacological Activities of 1, 3, 4 Thiadiazole Derivatives Review. Int J Pharm Biol Sci Arch 2013; 4: 256-64.
[28]
Altıntop MD, Ciftci HI, Radwan MO, et al. Design, synthesis, and biological evaluation of novel 1, 3, 4-thiadiazole derivatives as potential antitumor agents against chronic myelogenous leukemia: striking effect of nitrothiazole moiety. Molecules 2017; 23(1): 59.
[http://dx.doi.org/10.3390/molecules23010059] [PMID: 29280989]
[29]
Popiołek Ł, Biernasiuk A, Malm A. New 5-substituted-1, 3, 4-thiadiazole-2 (3H)-thione Derivatives: Synthesis and their in vitro antimicrobial properties. Chem Sci Int J 2015; 24: 136-43.
[30]
Serban G. Synthetic Compounds with 2-Amino-1,3,4-Thiadiazole Moiety Against Viral Infections. Molecules 2020; 25(4): 942.
[http://dx.doi.org/10.3390/molecules25040942] [PMID: 32093125]
[31]
El-Sayed Ali T. Synthesis of some novel pyrazolo[3,4-b]pyridine and pyrazolo[3,4-d]pyrimidine derivatives bearing 5,6-diphenyl-1,2,4-triazine moiety as potential antimicrobial agents. Eur J Med Chem 2009; 44(11): 4385-92.
[http://dx.doi.org/10.1016/j.ejmech.2009.05.031] [PMID: 19586688]
[32]
Abdel-Monem WR. Synthesis and Antimicrobial Activity of Some New Nitrogen Heterocyclic Systems Bearing 1, 2, 4-Triazine Moiety. Eur J Med Chem 2008; 43: 449-55.
[33]
Abou-Elregal MK, Mohamed AT, Youssef AS, Hemdan MM, Samir SS, Abou-Elmagd WS. Synthesis and antitumor activity evaluation of some 1, 2, 4-triazine and fused triazine derivatives. Synth Commun 2018; 48(18): 2347-57.
[http://dx.doi.org/10.1080/00397911.2018.1482350]
[34]
Dubey V, Pathak M, Bhat HR, Singh UP. Design, facile synthesis, and antibacterial activity of hybrid 1,3,4-thiadiazole-1,3,5- triazine derivatives tethered via -S- bridge. Chem Biol Drug Des 2012; 80(4): 598-604.
[http://dx.doi.org/10.1111/j.1747-0285.2012.01433.x] [PMID: 22716235]
[35]
Saad HA, Youssef MM, Mosselhi MA. Microwave assisted synthesis of some new fused 1,2,4-triazines bearing thiophene moieties with expected pharmacological activity. Molecules 2011; 16(6): 4937-57.
[http://dx.doi.org/10.3390/molecules16064937] [PMID: 21677606]
[36]
Pogorelčnik B, Janežič M, Sosič I, Gobec S, Solmajer T, Perdih A. 4,6-Substituted-1,3,5-triazin-2(1H)-ones as monocyclic catalytic inhibitors of human DNA topoisomerase IIα targeting the ATP binding site. Bioorg Med Chem 2015; 23(15): 4218-29.
[http://dx.doi.org/10.1016/j.bmc.2015.06.049] [PMID: 26183545]
[37]
Desai NC, Makwana AH, Rajpara KM. Synthesis and study of 1, 3, 5-triazine based thiazole derivatives as antimicrobial agents. J Saudi Chem Soc 2016; 20: S334-41.
[http://dx.doi.org/10.1016/j.jscs.2012.12.004]
[38]
Arunkumar S, Ilango K, Ravindar B, Ramalakshmi N. Synthesis and biological evaluation of some novel triazolo, thiadiazole derivatives of gallic acid. Pharma Chem 2009; 1(1): 70-7.
[39]
Wang Q, de Oliveira EF, Alborzi S, Bastarrachea LJ, Tikekar RV. On mechanism behind UV-A light enhanced antibacterial activity of gallic acid and propyl gallate against Escherichia coli O157:H7. Sci Rep 2017; 7(1): 8325.
[http://dx.doi.org/10.1038/s41598-017-08449-1] [PMID: 28814799]
[40]
Contreras A, Maxwell A. gyrB mutations which confer coumarin resistance also affect DNA supercoiling and ATP hydrolysis by Escherichia coli DNA gyrase. Mol Microbiol 1992; 6(12): 1617-24.
[http://dx.doi.org/10.1111/j.1365-2958.1992.tb00886.x] [PMID: 1323022]
[41]
del Valle P, García-Armesto MR, de Arriaga D, González- Donquiles C, Rodríguez-Fernández P, Rúa J. Antimicrobial activity of kaempferol and resveratrol in binary combinations with parabens or propyl gallate against Enterococcus faecalis. Food Control 2016; 61: 213-20.
[http://dx.doi.org/10.1016/j.foodcont.2015.10.001]
[42]
Jones ME, Draghi DC, Thornsberry C, Karlowsky JA, Sahm DF, Wenzel RP. Emerging resistance among bacterial pathogens in the intensive care unit--a European and North American Surveillance study (2000-2002). Ann Clin Microbiol Antimicrob 2004; 3(1): 14.
[http://dx.doi.org/10.1186/1476-0711-3-14] [PMID: 15283864]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 17
ISSUE: 7
Year: 2021
Published on: 08 December, 2020
Article ID: e010621188864
Pages: 10
DOI: 10.2174/1573407216999201208204054
Price: $65

Article Metrics

PDF: 75
HTML: 1
EPUB: 1
PRC: 1