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Current Bioactive Compounds

Author(s): Adinath D. Badar, Shubham M. Sulakhe, Mahesh B. Muluk, Naziya N. M. A. Rehman, Prashant P. Dixit, Prafulla B. Choudhari, Giribala M. Bondle and Kishan P. Haval*

DOI: 10.2174/1573407216999200911121853

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Synthesis, Antimicrobial Evaluation and Docking Study of Novel Thiosemicarbazone Clubbed with 1,2,3-Triazoles

Article ID: e010621185856 Pages: 10

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Abstract

Background: Thiosemicarbazone, 1,2,3-triazole and their derivatives received great pharmaceutical importance due to their prominent biological activities. In the present study, the molecular hybrid thiosemicarbazone-1,2,3-triazoles derivatives were synthesized and screened for their antimicrobial activities.

Methods: A series of thiosemicarbazone clubbed with 1,2,3-triazole derivatives were synthesized via click chemistry approach in good yields. The structures of synthesized compounds were assigned by their spectral data. The in vitro antimicrobial activity was performed by the agar well diffusion method. A molecular docking study was performed to identify the possible mode of action of synthesized derivatives.

Results: The compounds 5d, 5h, 5i and 5k exhibited excellent antimicrobial activities against both antibacterial and antifungal pathogens. The active thiosemicarbazone-1,2,3-triazole derivatives showed excellent binding affinity towards DNA gyrase.

Conclusion: The molecular hybrid thiosemicarbazone-1,2,3-triazole derivatives were synthesized. The newly synthesized compounds were evaluated for their antimicrobial activities. Few of the thiosemicarbazone-1,2,3-triazoles derivatives have exhibited good antimicrobial activities. They have shown excellent binding affinity towards DNA gyrase.

Keywords: 1, 2, 3-triazole, thiosemicarbazone, antimicrobial Activity, molecular Docking Study, click Chemistry.

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[1]
Narang R, Kumar R, Kalra S, et al. Recent advancements in mechanistic studies and structure activity relationship of FoF1 ATP synthase inhibitor as antimicrobial agent. Eur J Med Chem 2019; 182111644
[http://dx.doi.org/10.1016/j.ejmech.2019.111644] [PMID: 31493745]
[2]
Bhagat K, Bhagat J, Gupta MK, et al. Design, Synthesis, Antimicrobial Evaluation, and Molecular Modeling Studies of Novel Indolinedione-Coumarin Molecular Hybrids. ACS Omega 2019; 4(5): 8720-30.
[http://dx.doi.org/10.1021/acsomega.8b02481] [PMID: 31459961]
[3]
Woodford N, Ellington MJ. The emergence of antibiotic resistance by mutation. Clin Microbiol Infect 2007; 13(1): 5-18.
[http://dx.doi.org/10.1111/j.1469-0691.2006.01492.x] [PMID: 17184282]
[4]
Llor C, Bjerrum L. Antimicrobial resistance: risk associated with antibiotic overuse and initiatives to reduce the problem. Ther Adv Drug Saf 2014; 5(6): 229-41.
[http://dx.doi.org/10.1177/2042098614554919] [PMID: 25436105]
[5]
Hrudey S, Hrudey E. Common Themes Contributing to Recent Drinking Water Disease Outbreaks in Affluent Nations. Water Supply 2019; 19: 1767-77.
[http://dx.doi.org/10.2166/ws.2019.051]
[6]
Kim H, Jang JH, Kim SC, Cho JH. Development of a novel hybrid antimicrobial peptide for targeted killing of Pseudomonas aeruginosa. Eur J Med Chem 2020; 185111814
[http://dx.doi.org/10.1016/j.ejmech.2019.111814] [PMID: 31678742]
[7]
Yates CM, Shaw DJ, Roe AJ, Woolhouse ME, Amyes SG. Enhancement of bacterial competitive fitness by apramycin resistance plasmids from non-pathogenic Escherichia coli. Biol Lett 2006; 2(3): 463-5.
[http://dx.doi.org/10.1098/rsbl.2006.0478] [PMID: 17148431]
[8]
(a) Mitchell TJ. The pathogenesis of streptococcal infections: from tooth decay to meningitis. Nat Rev Microbiol 2003; 1(3): 219-30.
[http://dx.doi.org/10.1038/nrmicro771] [PMID: 15035026] ; (b) Sansonetti PJ. War and peace at mucosal surfaces. Nat Rev Immunol 2004; 4(12): 953-64.
[http://dx.doi.org/10.1038/nri1499] [PMID: 15573130]
[9]
(a) Qiu Y, Chan ST, Lin L, et al. Design, synthesis and biological evaluation of antimicrobial diarylimine and -amine compounds targeting the interaction between the bacterial NusB and NusE proteins. Eur J Med Chem 2019; 178: 214-31.
[http://dx.doi.org/10.1016/j.ejmech.2019.05.090] [PMID: 31185412] ; (b) Sahu A, Sahu P, Agrawal R. Synthesis, Pharmacological and Toxicological Screening of Penicillin-Triazole Conjugates (PNTCs). ACS Omega 2019; 4(17): 17230-5.
[http://dx.doi.org/10.1021/acsomega.9b01724] [PMID: 31656896]
[10]
(a) Dheer D, Singh V, Shankar R. Medicinal attributes of 1,2,3-triazoles: Current developments. Bioorg Chem 2017; 71: 30-54.
[http://dx.doi.org/10.1016/j.bioorg.2017.01.010] ; (b) Kumar R, Singh D, Singh J, Singh H, Roy RK, Chaudhary A. 1,2,3-Triazine Scaffold as a Potent Biologically Active Moiety: A Mini Review. Mini-Rev Med Chem 2014; 14: 72-83.
[http://dx.doi.org/10.1021/cr200409f] [PMID: 23531040]
[11]
(a) Nalawade J, Shinde A, Chavan A, et al. Synthesis of new thiazolyl-pyrazolyl-1,2,3-triazole derivatives as potential antimicrobial agents. Eur J Med Chem 2019; 179: 649-59.
[http://dx.doi.org/10.1016/j.ejmech.2019.06.074] [PMID: 31279297] ; (b) Thirumurugan P, Matosiuk D, Jozwiak K. Click chemistry for drug development and diverse chemical-biology applications. Chem Rev 2013; 113(7): 4905-79.
[http://dx.doi.org/10.1021/cr200409f] [PMID: 23531040]
[12]
Aher NG, Pore VS, Mishra NN, Shukla PK, Gonnade RG. Design and synthesis of bile acid-based amino sterols as antimicrobial agents. Bioorg Med Chem Lett 2009; 19(18): 5411-4.
[http://dx.doi.org/10.1016/j.bmcl.2009.07.117] [PMID: 19679476]
[13]
Yang Y, Rasmussen BA, Shlaes DM. Class A beta-lactamases-enzyme-inhibitor interactions and resistance. Pharmacol Ther 1999; 83(2): 141-51.
[http://dx.doi.org/10.1016/S0163-7258(99)00027-3] [PMID: 10511459]
[14]
(a) Dhumal ST, Deshmukh AR, Kharat KR, Sathe BR, Chavan SS, Mane RA. Copper fluorapatite assisted synthesis of new 1,2,3-triazoles bearing a benzothiazolyl moiety and their antibacterial and anticancer activities. New J Chem 2019; 43: 7663-73.
[http://dx.doi.org/10.1039/C9NJ00377K] ; (b) Wu M-J, Wu D-M, Chen J-B, et al. Synthesis and anti-proliferative activity of allogibberic acid derivatives containing 1,2,3-triazole pharmacophore. Bioorg Med Chem Lett 2018; 28(14): 2543-9.
[http://dx.doi.org/10.1016/j.bmcl.2018.05.038] [PMID: 29884535]
[15]
(a) Marvadi SK, Krishna VS, Sinegubova EO, et al. 5-Chloro-2-thiophenyl-1,2,3-triazolylmethyldihydroquinolines as dual inhibitors of Mycobacterium tuberculosis and influenza virus: Synthesis and evaluation. Bioorg Med Chem Lett 2019; 29(18): 2664-9.
[http://dx.doi.org/10.1016/j.bmcl.2019.07.040] [PMID: 31375291] ; (b) Thanh ND, Hai DS, Ha NTT, et al. Synthesis, biological evaluation and molecular docking study of 1,2,3-1H-triazoles having 4H-pyrano[2,3-d]pyrimidine as potential Mycobacterium tuberculosis protein tyrosine phosphatase B inhibitors. Bioorg Med Chem Lett 2019; 29(2): 164-71.
[http://dx.doi.org/10.1016/j.bmcl.2018.12.009] [PMID: 30551903]
[16]
Shaikh MH, Subhedar DD, Khan FAK, et al. Synthesis of Novel Triazole‐incorporated Isatin Derivatives as Antifungal, Antitubercular, and Antioxidant Agents and Molecular Docking Study. J Heterocycl Chem 2017; 54: 413-21.
[http://dx.doi.org/10.1002/jhet.2598]
[17]
Arif MN, Nadeem H, Paracha RZ, Khan A, Imran M, Alid F. Synthesis, Anti-inflammatory, Antimicrobial Potential and Molecular Docking Studies of 4,5-Disubstituted-1,2,4-Triazole Thioacetate Derivatives. Lett Drug Des Discov 2019; 16: 734-45.
[http://dx.doi.org/10.2174/1570180815666180810122226]
[18]
(a) Kaushik CP, Luxmi R, Kumar M, Singh D, Kumar K, Pahwa A. One-pot facile synthesis, crystal structure and antifungal activity of 1,2,3-triazoles bridged with amine-amide functionalities. Synth Commun 2019; 49: 118-28.
[http://dx.doi.org/10.1080/00397911.2018.1544371] ; (b) Khare SP, Deshmukh TR, Sangshetti JN, et al. Design, Synthesis and Molecular Docking Studies of Novel Triazole-Chromene Conjugates as Antitubercular, Antioxidant and Antifungal Agents. ChemistrySelect 2018; 3: 13113-22.
[http://dx.doi.org/10.1002/slct.201801859]
[19]
Saeedi M, Ansari S, Mahdavi M, et al. Synthesis of Novel 1,2,3-Triazole-dihydro[3,2-c]chromenones as Acetylcholinesterase Inhibitors. Synth Commun 2015; 45: 2311-8.
[http://dx.doi.org/10.1080/00397911.2015.1077971]
[20]
Wang G, Peng Z, Wang J, Li J, Li X. Synthesis and biological evaluation of novel 2,4,5-triarylimidazole-1,2,3-triazole derivatives via click chemistry as α-glucosidase inhibitors. Bioorg Med Chem Lett 2016; 26(23): 5719-23.
[http://dx.doi.org/10.1016/j.bmcl.2016.10.057] [PMID: 27810241]
[21]
(a) Tornøe CW, Christensen C, Meldal M. Triazoles by Regiospecific Copper(I)-Catalyzed 1,3-Dipolar Cycloadditions of Terminal Alkynes to Azides. J Org Chem 2002; 67: 3057-64.
[http://dx.doi.org/10.1021/jo011148j] [PMID: 11975567] ; (b) Rostovtsev VV, Green LG, Fokin VV, Sharpless KB. A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective “ligation” of azides and terminal alkynes. Angew Chem Int Ed Engl 2002; 41(14): 2596-9.
[http://dx.doi.org/10.1002/1521-3773(20020715)41:14<2596::AID-ANIE2596>3.0.CO;2-4] [PMID: 12203546]
[22]
Liang Z, Huang Y, Wang S, Deng X. Synthesis and Biological Evaluation of Some Pyrazole Derivatives, Containing (Thio) Semicarbazide, as Dual Anti-Inflammatory Antimicrobial Agents. Lett Drug Des Discov 2019; 16: 1020-30.
[http://dx.doi.org/10.2174/1570180816666190325163117]
[23]
(a) Bhat MA, Al-Tahhan M, Al-Omar MA, Naglah AM, Al-Dhfyan A. Design and Synthesis of Novel Thiosemicarbazones as Potent Anti-breast Cancer Agents. Lett Drug Des Discov 2019; 16: 446-52.
[http://dx.doi.org/10.2174/1570180815666181008100944] ; (b) Yee EMH, Brandl MB, Black DS, Vittorio O, Kumar N. Synthesis of isoflavene-thiosemicarbazone hybrids and evaluation of their anti-tumor activity. Bioorg Med Chem Lett 2017; 27(11): 2454-8.
[http://dx.doi.org/10.1016/j.bmcl.2017.04.002] [PMID: 28408225]
[24]
Moreno-Rodríguez A, Salazar-Schettino PM, Bautista JL, et al. In vitro antiparasitic activity of new thiosemicarbazones in strains of Trypanosoma cruzi. Eur J Med Chem 2014; 87: 23-9.
[http://dx.doi.org/10.1016/j.ejmech.2014.09.027] [PMID: 25238291]
[25]
Sroor FM, Khatab TK, Basyouni WM, El-Bayouki KAM. Synthesis and molecular docking studies of some new thiosemicarbazone derivatives as HCV polymer aseinhibitors. Synth Commun 2019; 49: 1444-56.
[http://dx.doi.org/10.1080/00397911.2019.1605443]
[26]
Abhale YK, Shinde A, Deshmukh KK, Nawale L, Sarkar D, Mhaske PC. Synthesis, antitubercular and antimicrobial potential of some new thiazole substituted thiosemicarbazide derivatives. Med Chem Res 2017; 26: 2557-67.
[http://dx.doi.org/10.1007/s00044-017-1955-1]
[27]
Abbas SY, Basyouni WM, El-Bayouki KAM, Dawood RM, Abdelhafez TH, Elawady MK. Efficient synthesis and anti-bovine viral diarrhea virus evaluation of 5-(aryldiazo)salicylaldehyde thiosemicarbazone derivatives. Synth Commun 2019; 49: 2411-6.
[http://dx.doi.org/10.1080/00397911.2019.1626893]
[28]
Soares MA, Almeida MA, Marins-Goulart C, Chaves OA, Echevarria A, de Oliveira MCC. Thiosemicarbazones as inhibitors of tyrosinase enzyme. Bioorg Med Chem Lett 2017; 27(15): 3546-50.
[http://dx.doi.org/10.1016/j.bmcl.2017.05.057] [PMID: 28583798]
[29]
Singh P, Jain J, Sinha R, Samad A, Kumar R, Malhotra M. Synthesis and screening of substituted thiosemicarbazone derivatives: an approach towards novel anticonvulsant search. Cent Nerv Syst Agents Med Chem 2011; 11(1): 60-5.
[http://dx.doi.org/10.2174/187152411794961112] [PMID: 21294704]
[30]
(a) Adole VA, More RA, Jagdale BS, Pawar TB, Chobe SS. Efficient Synthesis, Antibacterial, Antifungal, Antioxidant and Cytotoxicity Study of 2-(2-Hydrazineyl)thiazole Derivatives. ChemistrySelect 2020; 5: 2778-86.
[http://dx.doi.org/10.1002/slct.201904609] ; (b) El-Helw EAE, Sallam HA, Elgubbi AS. Antioxidant activity of some N-heterocycles derived from 2-(1-(2-oxo-2H-chromen-3-yl)ethylidene) hydrazinecarbothioamide. Synth Commun 2019; 49: 2651-61.
[http://dx.doi.org/10.1080/00397911.2019.1638938]
[31]
Palanimuthu D, Poon R, Sahni S, et al. A novel class of thiosemicarbazones show multi-functional activity for the treatment of Alzheimer’s disease. Eur J Med Chem 2017; 139: 612-32.
[http://dx.doi.org/10.1016/j.ejmech.2017.08.021] [PMID: 28841514]
[32]
Ramadan SK, Sallam HA. Synthesis, Spectral Characterization, Cytotoxic, and Antimicrobial Activities of Some Novel Heterocycles Utilizing 1,3-Diphenylpyrazole-4-carboxaldehyde Thiosemicarbazone. J Heterocycl Chem 2018; 55: 1942-54.
[http://dx.doi.org/10.1002/jhet.3232]
[33]
(a) Abdel-Galil E, Girges MM, Said GE. Synthesis and Biological Studies of Some New Thiazoles, Hydrazones and Azine Derivatives Based on 3,5- Diphenylcyclohex-2-en-1-one. ChemistrySelect 2020; 5: 3075-9.
[http://dx.doi.org/10.1002/slct.201904770] ; (b) He Z, Qiao H, Yang F, et al. Novel thiosemicarbazone derivatives containing indole fragment as potent and selective anticancer agent. Eur J Med Chem 2019; 184111764
[http://dx.doi.org/10.1016/j.ejmech.2019.111764] [PMID: 31614257] ; (c) Shakya B, Shahi N, Ahmad F, Yadav PN, Pokharel YR. 2-Pyridineformamide N(4)-ring incorporated thiosemicarbazones inhibit MCF-7 cells by inhibiting JNK pathway. Bioorg Med Chem Lett 2019; 29(13): 1677-81.
[http://dx.doi.org/10.1016/j.bmcl.2019.04.031] [PMID: 31053506]
[34]
(a) Chauhan S, Verma V, Kumar D, Kumar A. Synthesis, antimicrobial evaluation and docking study of triazole containing triaryl-1H-imidazole. Synth Commun 2019; 49: 1427-35.
[http://dx.doi.org/10.1080/00397911.2019.1600192] ; (b) Lal K, Yadav P, Kumar A. Synthesis, characterization and antimicrobial activity of 4-((1-benzyl/phenyl-1H-1,2,3-triazol-4-yl)methoxy)benzaldehyde analogues. Med Chem Res 2016; 25: 644-52.
[http://dx.doi.org/10.1007/s00044-016-1515-0] ; (c) Teng Y, Qin Y, Song D, et al. A novel series of 11-O-carbamoyl-3-O-descladinosyl clarithromycin derivatives bearing 1,2,3-triazole group: Design, synthesis and antibacterial evaluation. Bioorg Med Chem Lett 2020; 30(2)126850
[http://dx.doi.org/10.1016/j.bmcl.2019.126850] [PMID: 31836439] ; (d) Marepu N, Yeturu S, Pal M. 1,2,3-Triazole fused with pyridine/pyrimidine as new template for antimicrobial agents: Regioselective synthesis and identification of potent N-heteroarenes. Bioorg Med Chem Lett 2018; 28(20): 3302-6.
[http://dx.doi.org/10.1016/j.bmcl.2018.09.021] [PMID: 30243590] ; (e) El-Sayed HA, Abdel Hamid AM, Mohammed SM, Moustafa AH. Design, synthesis, and antimicrobial activity of fluorophore 1,2,3-triazoles linked nicotinonitrile derivatives. Synth Commun 2019; 49: 2096-105.
[http://dx.doi.org/10.1080/00397911.2019.1616760] ; (f) Tittal RK, Yadav P, Lal K, Kumar A. Synthesis, molecular docking and DFT studies on biologically active 1, 4-disubstituted-1, 2, 3-triazole-semicarbazone hybrid molecules. New J Chem 2019; 43: 8052-8.
[http://dx.doi.org/10.1039/C9NJ00473D] ; (g) Singh H, Singh JV, Gupta MK, et al. Triazole tethered isatin-coumarin based molecular hybrids as novel antitubulin agents: Design, synthesis, biological investigation and docking studies. Bioorg Med Chem Lett 2017; 27(17): 3974-9.
[http://dx.doi.org/10.1016/j.bmcl.2017.07.069] [PMID: 28797799]
[35]
(a) Muluk MB, Dhumal ST, Phatak PS, et al. Synthesis, antimicrobial activity, and molecular docking study of formylnaphthalenyloxymethyl‐triazolyl‐N‐phenylacetamides. J Heterocycl Chem 2019; 56: 2411-8.
[http://dx.doi.org/10.1002/jhet.3628] ; (b) Muluk MB, Dhumal ST, Rehman NNMA, Dixit PP, Kharat KR, Haval KP. Synthesis, Anticancer and Antimicrobial Evaluation of New (E)‐N′‐Benzylidene‐2‐(2‐ethylpyridin‐4‐yl)‐4‐methylthiazole‐5‐carbohydrazides. ChemistrySelect 2019; 4: 8993-7.
[http://dx.doi.org/10.1002/slct.201902030]
[36]
Phatak PS, Sathe BP, Dhumal ST, et al. Synthesis, antimicrobial evaluation and docking studies of substituted acetylphenoxymethyl-triazolyl-N-phenylacetamides. J Heterocycl Chem 2019; 56: 1928-38.
[http://dx.doi.org/10.1002/jhet.3568]
[37]
(a) Muluk MB, Phatak PS, Pawar SB, et al. Synthesis, antimicrobial and antioxidant activities of new pyridyl and thiazolyl bearing carbohydrazides. J Chin Chem Soc (Taipei) 2019; 66: 1507-17.
[http://dx.doi.org/10.1002/jccs.201900198] ; (b) Thalji RK, Raha K, Andreotti D, et al. Structure-guided design of antibacterials that allosterically inhibit DNA gyrase. Bioorg Med Chem Lett 2019; 29(11): 1407-12.
[http://dx.doi.org/10.1016/j.bmcl.2019.03.029] [PMID: 30962087]
[38]
Phatak PS, Bakale RD, Dhumal ST, et al. Synthesis, antitubercular evaluation and molecular docking studies of phthalimide bearing 1,2,3-triazoles. Synth Commun 2019; 49: 2017-28.
[http://dx.doi.org/10.1080/00397911.2019.1614630]