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Current Organic Chemistry

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ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

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Research Article

Design, Synthesis, and Antimicrobial Evaluation of Novel Sulfonamide Modified with Azoles

Author(s): Pratibha Periwal, Ashwani Kumar, Vikas Verma*, Devinder Kumar, Mahavir Parshad, Meenakshi Bhatia and Sourbh Thakur

Volume 28, Issue 7, 2024

Published on: 13 March, 2024

Page: [558 - 572] Pages: 15

DOI: 10.2174/0113852728296342240216074100

Price: $65

Abstract

Sulfonamide, imidazole, and triazole chemical nuclei possess good antimicrobial potential. This study aimed to amalgamate sulfonamide, imidazole, and triazole moieties in a single molecular framework with the intent of improving their antimicrobial activities. The objective of this study was the synthesis of conjugates containing sulfonamide and azole moieties along with in vitro and in silico evaluation as antimicrobial candidates. A series of sulfonamide-modified azoles (7a-r) was synthesized by multicomponent condensation of 1,2-dicarbonyl compounds, ammonium acetate and aryl-substituted aldehydes in glacial acetic acid. The structure of synthesized molecules was elucidated with the help of various spectroscopic techniques, such as FTIR, NMR, and HRMS. The target molecules were tested for in vitro antimicrobial potency against four bacterial strains and two fungal strains. Molecules 7c (MIC 0.0188 μmol/mL), 7f (MIC 0.0170 μmol/mL) and 7i (MIC 0.0181 μmol/mL) were most active against S. aureus and C. albicans. Against E. coli, molecules 7d (MIC 0.0179 μmol/mL), 7f (MIC 0.0170 μmol/mL) and 7i (MIC 0.0181 μmol/mL) were found to be highly active. Moreover, the binding conformations were investigated by in silico molecular docking, and QTAIM (Quantitative theory of atoms in the molecule) analysis was also performed. Molecular properties, such as the heat of formation, HOMO energy, LUMO energy and COSMO volume, were found to be in direct correlation with the antimicrobial potency of molecules 7c, 7f and 7i against S. aureus and C. albicans. All the synthesized molecules were more potent than clinically approved sulfonamides, namely sulfadiazine and sulfabenzamide.

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[1]
Payne, D. J. Microbiology. Desperately seeking new antibiotics. Science, 2008, 321(5896), 1644-1645.
[http://dx.doi.org/10.1126/science.1164586] [PMID: 18801989]
[2]
World Health Organisation (WHO). 2023. Available from: https://www.who.int/
[3]
Supuran, C. Special issue: Sulfonamides. Molecules, 2017, 22(10), 1642.
[http://dx.doi.org/10.3390/molecules22101642] [PMID: 28961201]
[4]
Al-Blewi, F.F.; Almehmadi, M.A.; Aouad, M.R.; Bardaweel, S.K.; Sahu, P.K.; Messali, M.; Rezki, N.; El Ashry, E.S.H. Design, synthesis, ADME prediction and pharmacological evaluation of novel benzimidazole-1,2,3-triazole-sulfonamide hybrids as antimicrobial and antiproliferative agents. Chem. Cent. J., 2018, 12(1), 110.
[http://dx.doi.org/10.1186/s13065-018-0479-1] [PMID: 30387018]
[5]
Ren, Y.; Ma, Y.; Cherukupalli, S.; Tavis, J.E.; Menéndez-Arias, L.; Liu, X.; Zhan, P. Discovery and optimization of benzenesulfonamides-based hepatitis B virus capsid modulators via contemporary medicinal chemistry strategies. Eur. J. Med. Chem., 2020, 206, 112714.
[http://dx.doi.org/10.1016/j.ejmech.2020.112714] [PMID: 32949990]
[6]
Shahzad, S.; Qadir, M.A.; Ahmed, M.; Ahmad, S.; Khan, M.J.; Gulzar, A.; Muddassar, M. Folic acid-sulfonamide conjugates as antibacterial agents: Design, synthesis and molecular docking studies. RSC Advances, 2020, 10(70), 42983-42992.
[http://dx.doi.org/10.1039/D0RA09051D] [PMID: 35514930]
[7]
Meşeli, T.; Doğan, Ş.D.; Gündüz, M.G.; Kökbudak, Z.; Skaro Bogojevic, S.; Noonan, T.; Vojnovic, S.; Wolber, G.; Nikodinovic-Runic, J. Design, synthesis, antibacterial activity evaluation and molecular modeling studies of new sulfonamides containing a sulfathiazole moiety. New J. Chem., 2021, 45(18), 8166-8177.
[http://dx.doi.org/10.1039/D1NJ00150G]
[8]
Potey, L.C.; Marathe, R.; Sable, P. In vitro anti-inflammatory activity of quinoxalinsulfonamides. Int. J. Chemtech Res., 2017, 10, 726-734.
[9]
Kumar, M.; Ramasamy, K.; Mani, V.; Mishra, R.K.; Majeed, A.B.A.; Clercq, E.D.; Narasimhan, B. Synthesis, antimicrobial, anticancer, antiviral evaluation and QSAR studies of 4-(1-aryl-2-oxo-1,2-dihydro-indol-3-ylideneamino)-N-substituted benzene sulfonamides. Arab. J. Chem., 2014, 7(4), 396-408.
[http://dx.doi.org/10.1016/j.arabjc.2012.12.005]
[10]
Mun, J.; Jabbar, A.A.; Devi, N.S.; Yin, S.; Wang, Y.; Tan, C.; Culver, D.; Snyder, J.P.; Van Meir, E.G.; Goodman, M.M. Design and in vitro activities of N-alkyl-N-[(8-R-2,2-dimethyl-2H-chromen-6-yl)methyl]heteroaryl-sulfonamides, novel, small-molecule hypoxia inducible factor-1 pathway inhibitors and anticancer agents. J. Med. Chem., 2012, 55(15), 6738-6750.
[http://dx.doi.org/10.1021/jm300752n] [PMID: 22746274]
[11]
Chibale, K.; Haupt, H.; Kendrick, H.; Yardley, V.; Saravanamuthu, A.; Fairlamb, A.H.; Croft, S.L. Antiprotozoal and cytotoxicity evaluation of sulfonamide and urea analogues of quinacrine. Bioorg. Med. Chem. Lett., 2001, 11(19), 2655-2657.
[http://dx.doi.org/10.1016/S0960-894X(01)00528-5] [PMID: 11551771]
[12]
Ezabadi, I.R.; Camoutsis, C.; Zoumpoulakis, P.; Geronikaki, A.; Soković, M.; Glamočilija, J.; Ćirić, A. Sulfonamide-1,2,4-triazole derivatives as antifungal and antibacterial agents: Synthesis, biological evaluation, lipophilicity, and conformational studies. Bioorg. Med. Chem., 2008, 16(3), 1150-1161.
[http://dx.doi.org/10.1016/j.bmc.2007.10.082] [PMID: 18053730]
[13]
Pandit, S.S.; Kulkarni, M.R.; Pandit, Y.B.; Lad, N.P.; Khedkar, V.M. Synthesis and in vitro evaluations of 6-(hetero)-aryl-imidazo[1,2-b]pyridazine-3-sulfonamide’s as an inhibitor of TNF-α production. Bioorg. Med. Chem. Lett., 2018, 28(1), 24-30.
[http://dx.doi.org/10.1016/j.bmcl.2017.11.026] [PMID: 29173945]
[14]
Hu, B.; Ellingboe, J.; Han, S.; Largis, E.; Lim, K.; Malamas, M.; Mulvey, R.; Niu, C.; Oliphant, A.; Pelletier, J.; Singanallore, T.; Sum, F.W.; Tillett, J.; Wong, V. Novel (4-piperidin-1-yl)-phenyl sulfonamides as potent and selective human beta(3) agonists. Bioorg. Med. Chem., 2001, 9(8), 2045-2059.
[http://dx.doi.org/10.1016/S0968-0896(01)00114-6] [PMID: 11504641]
[15]
Roush, W.R.; Gwaltney, S.L.; Cheng, J.; Scheidt, K.A.; McKerrow, J.H.; Hansell, E. Vinyl sulfonate esters and vinyl sulfonamides: Potent, irreversible inhibitors of cysteine proteases. J. Am. Chem. Soc., 1998, 120(42), 10994-10995.
[http://dx.doi.org/10.1021/ja981792o]
[16]
Wan, Y.; Fang, G.; Chen, H.; Deng, X.; Tang, Z. Sulfonamide derivatives as potential anti-cancer agents and their SARs elucidation. Eur. J. Med. Chem., 2021, 226, 113837.
[http://dx.doi.org/10.1016/j.ejmech.2021.113837] [PMID: 34530384]
[17]
Küçükbay, H.; Buğday, N.; Küçükbay, F.Z.; Berrino, E.; Bartolucci, G.; Del Prete, S.; Capasso, C.; Supuran, C.T. Synthesis and carbonic anhydrase inhibitory properties of novel 4-(2-aminoethyl)benzenesulfonamide-dipeptide conjugates. Bioorg. Chem., 2019, 83, 414-423.
[http://dx.doi.org/10.1016/j.bioorg.2018.11.003] [PMID: 30419497]
[18]
Buğday, N.; Küçükbay, F.Z.; Küçükbay, H.; Bua, S.; Bartolucci, G.; Leitans, J.; Kazaks, A.; Tars, K.; Supuran, C.T. Synthesis of novel dipeptide sulfonamide conjugates with effective carbonic anhydrase I, II, IX, and XII inhibitory properties. Bioorg. Chem., 2018, 81, 311-318.
[http://dx.doi.org/10.1016/j.bioorg.2018.08.032] [PMID: 30176570]
[19]
Küçükbay, F.Z.; Küçükbay, H.; Tanc, M.; Supuran, C.T. Synthesis and carbonic anhydrase I, II, IV and XII inhibitory properties of N-protected amino acid - sulfonamide conjugates. J. Enzyme Inhib. Med. Chem., 2016, 31(6), 1476-1483.
[http://dx.doi.org/10.3109/14756366.2016.1147438] [PMID: 26899532]
[20]
Brown, E.D.; Wright, G.D. Antibacterial drug discovery in the resistance era. Nature, 2016, 529(7586), 336-343.
[http://dx.doi.org/10.1038/nature17042] [PMID: 26791724]
[21]
Küçükbay, H.; Durmaz, R.; Okyucu, N.; Günal, S. Antifungal activity of some bis-5-methylbenzimidazole compounds. Folia Microbiol., 2003, 48(5), 679-681.
[http://dx.doi.org/10.1007/BF02993478] [PMID: 14976728]
[22]
Güngördü, A.; Sireci, N.; Küçükbay, H.; Birhanli, A.; Ozmen, M. Evaluation of in vitro and in vivo toxic effects of newly synthesized benzimidazole-based organophosphorus compounds. Ecotoxicol. Environ. Saf., 2013, 87, 23-32.
[http://dx.doi.org/10.1016/j.ecoenv.2012.10.007] [PMID: 23116621]
[23]
Shabalin, D.A.; Camp, J.E. Recent advances in the synthesis of imidazoles. Org. Biomol. Chem., 2020, 18(21), 3950-3964.
[http://dx.doi.org/10.1039/D0OB00350F] [PMID: 32419000]
[24]
Deswal, L.; Verma, V.; Kumar, D.; Kumar, A.; Bhatia, M.; Deswal, Y.; Kumar, A. Development of novel anti-infective and antioxidant azole hybrids using a wet and dry approach. Future Med. Chem., 2021, 13(11), 975-991.
[http://dx.doi.org/10.4155/fmc-2020-0321] [PMID: 33896215]
[25]
Punia, S.; Verma, V.; Kumar, D.; Kumar, A.; Deswal, L.; Singh, G.; Sahoo, S.C. Pyrazolyl-Imidazole clubbed 1,2,3-triazoles: Synthesis, structure explication and antimicrobial evaluation. J. Mol. Struct., 2022, 1262, 133060.
[http://dx.doi.org/10.1016/j.molstruc.2022.133060]
[26]
Chauhan, S.; Verma, V.; Kumar, D.; Gupta, R.; Gupta, S.; Bajaj, A.; Kumar, A.; Parshad, M. N-Heterocycles hybrids: Synthesis, antifungal and antibiofilm evaluation. Synth. Commun., 2022, 52(6), 898-911.
[http://dx.doi.org/10.1080/00397911.2022.2056852]
[27]
Yao, J.; Takenaga, K.; Koshikawa, N.; Kida, Y.; Lin, J.; Watanabe, T.; Maru, Y.; Hippo, Y.; Yamamoto, S.; Zhu, Y.; Nagase, H. Anticancer effect of a pyrrole‐imidazole polyamide‐triphenylphosphonium conjugate selectively targeting a common mitochondrial DNA cancer risk variant in cervical cancer cells. Int. J. Cancer, 2023, 152(5), 962-976.
[http://dx.doi.org/10.1002/ijc.34319] [PMID: 36214789]
[28]
Nikitin, E.A.; Shpakovsky, D.B.; Tyurin, V.Y.; Kazak, A.A.; Gracheva, Y.A.; Vasilichin, V.A.; Pavlyukov, M.S.; Mironova, E.M.; Gontcharenko, V.E.; Lyssenko, K.A.; Antonets, A.A.; Dubova, L.G.; Shevtsov, P.N.; Shevtsova, E.F.; Shamraeva, M.A.; Shtil, A.A.; Milaeva, E.R. Novel organotin complexes with phenol and imidazole moieties for optimized antitumor properties. J. Organomet. Chem., 2022, 959, 122212.
[http://dx.doi.org/10.1016/j.jorganchem.2021.122212]
[29]
Deswal, Y.; Asija, S.; Tufail, A.; Dubey, A.; Deswal, L.; Kumar, N.; Saroya, S.; Kirar, J.S.; Gupta, N.M. Instigating the in vitro antidiabetic activity of new tridentate Schiff base ligand appended M(II) complexes: From synthesis, structural characterization, quantum computational calculations to molecular docking, and molecular dynamics simulation studies. Appl. Organomet. Chem., 2023, 37(4), e7050.
[http://dx.doi.org/10.1002/aoc.7050]
[30]
Deswal, L.; Verma, V.; Kirar, J.S.; Kumar, D.; Deswal, Y.; Kumar, A.; Bhatia, M. Benzimidazole-1,2,3-triazole-piperazine hybrids: Design, synthesis, antidiabetic evaluation and molecular modelling studies. Res. Chem. Intermed., 2023, 49(3), 1059-1083.
[http://dx.doi.org/10.1007/s11164-022-04921-4]
[31]
Ali, S.; Ali, M.; Khan, A.; Ullah, S.; Waqas, M.; Al-Harrasi, A.; Latif, A.; Ahmad, M.; Saadiq, M. Novel 5-(Arylideneamino)-1H-Benzo[d]imidazole-2-thiols as potent anti-diabetic agents: Synthesis, in vitro α-glucosidase inhibition, and molecular docking studies. ACS Omega, 2022, 7(48), 43468-43479.
[http://dx.doi.org/10.1021/acsomega.2c03854] [PMID: 36506132]
[32]
Deswal, L.; Verma, V.; Kumar, D.; Deswal, Y.; Kumar, A.; Kumar, R.; Parshad, M.; Bhatia, M. Synthesis, antimicrobial and α-glucosidase inhibition of new benzimidazole-1,2,3-triazole-indoline derivatives: A combined experimental and computational venture. Chem. Zvesti, 2022, 76(12), 7607-7622.
[http://dx.doi.org/10.1007/s11696-022-02436-1]
[33]
Nikitina, P.A.; Basanova, E.I.; Nikolaenkova, E.B.; Os’kina, I.A.; Serova, O.A.; Bormotov, N.I.; Shishkina, L.N.; Perevalov, V.P.; Tikhonov, A.Y. Synthesis of esters and amides of 2-aryl-1-hydroxy-4-methyl-1H-imidazole-5-carboxylic acids and study of their antiviral activity against orthopoxviruses. Bioorg. Med. Chem. Lett., 2023, 79, 129080.
[http://dx.doi.org/10.1016/j.bmcl.2022.129080] [PMID: 36414175]
[34]
Jiang, X.; Sharma, P.P.; Rathi, B.; Ji, X.; Hu, L.; Gao, Z.; Kang, D.; Wang, Z.; Xie, M.; Xu, S.; Zhang, X.; De Clercq, E.; Cocklin, S.; Pannecouque, C.; Dick, A.; Liu, X.; Zhan, P. Discovery of novel 1,2,4‐triazole phenylalanine derivatives targeting an unexplored region within the interprotomer pocket of the HIV capsid protein. J. Med. Virol., 2022, 94(12), 5975-5986.
[http://dx.doi.org/10.1002/jmv.28064] [PMID: 35949003]
[35]
Dong, H.R.; Wu, J.G.; Huo, G.Y. Design, synthesis and biological studies of some new imidazole-1,2,3-triazole hybrid derivatives. J. Mol. Struct., 2022, 1256, 132516.
[http://dx.doi.org/10.1016/j.molstruc.2022.132516]
[36]
De, S.; Aamna, B.; Sahu, R.; Parida, S.; Behera, S.K.; Dan, A.K. Seeking heterocyclic scaffolds as antivirals against dengue virus. Eur. J. Med. Chem., 2022, 240, 114576.
[http://dx.doi.org/10.1016/j.ejmech.2022.114576] [PMID: 35816877]
[37]
Fan, Y.L.; Jin, X.H.; Huang, Z.P.; Yu, H.F.; Zeng, Z.G.; Gao, T.; Feng, L.S. Recent advances of imidazole-containing derivatives as anti-tubercular agents. Eur. J. Med. Chem., 2018, 150, 347-365.
[http://dx.doi.org/10.1016/j.ejmech.2018.03.016] [PMID: 29544148]
[38]
Nandwana, N.K.; Singh, R.P.; Patel, O.P.S.; Dhiman, S.; Saini, H.K.; Jha, P.N.; Kumar, A. Design and synthesis of imidazo/benzimidazo [1, 2-c] quinazoline derivatives and evaluation of their antimicrobial activity. ACS Omega, 2018, 3(11), 16338-16346.
[http://dx.doi.org/10.1021/acsomega.8b01592] [PMID: 31458269]
[39]
Hao, S.; Cheng, X.; Wang, X.; An, R.; Xu, H.; Guo, M.; Li, C.; Wang, Y.; Hou, Z.; Guo, C. Design, synthesis and biological evaluation of novel carbohydrate-based sulfonamide derivatives as antitumor agents. Bioorg. Chem., 2020, 104, 104237.
[http://dx.doi.org/10.1016/j.bioorg.2020.104237] [PMID: 32911194]
[40]
Jian-Song Gao, Q.L.; Wu, B.W.; Li, D.; Shi, L.; Zhu, T.; Lou, J.F.; Jin, C.Y.; Zhang, Y.B.; Zhang, S.Y.; Liu, H.M. Novel tertiary sulfonamide derivatives containing benzimidazole moiety as potent anti-gastric cancer agents: Design, synthesis and SAR studies. Eur. J. Med. Chem., 2019, 183, 111731.
[http://dx.doi.org/10.1016/j.ejmech.2019.111731] [PMID: 31577977]
[41]
Batra, N.; Rajendran, V.; Wadi, I.; Lathwal, A.; Dutta, R.K.; Ghosh, P.C.; Gupta, R.D.; Nath, M. Synthesis, characterization, and antiplasmodial efficacy of sulfonamide‐appended [1,2,3]‐triazoles. J. Heterocycl. Chem., 2020, 57(4), 1625-1636.
[http://dx.doi.org/10.1002/jhet.3888]
[42]
Deswal, L.; Verma, V.; Kumar, D.; Kaushik, C.P.; Kumar, A.; Deswal, Y.; Punia, S. Synthesis and antidiabetic evaluation of benzimidazole‐tethered 1,2,3‐triazoles. Arch. Pharm., 2020, 353(9), 2000090.
[http://dx.doi.org/10.1002/ardp.202000090] [PMID: 32567729]
[43]
Chauhan, S.; Verma, V.; Kumar, D.; Kumar, A. Synthesis, antimicrobial evaluation and docking study of triazole containing triaryl-1H-imidazole. Synth. Commun., 2019, 49(11), 1427-1435.
[http://dx.doi.org/10.1080/00397911.2019.1600192]
[44]
Periwal, P.; Verma, V.; Kumar, D.; Kumar, A.; Bhatia, M.; Thakur, S.; Parshad, M. Novel azole–sulfonamide conjugates as potential antimicrobial candidates: Synthesis and biological assessment. Future Medicinal Chemistry, 2024.
[http://dx.doi.org/10.4155/fmc-2023-0251]
[45]
Gönül, Z.; Öztürk, D.A.; Küçükbay, F.; Tekin, S.; Tekin, Z.; Küçükbay, H. Antioxidant and cytotoxic properties of some new dipeptide‐indole conjugates. J. Heterocycl. Chem., 2023, 60(1), 86-95.
[http://dx.doi.org/10.1002/jhet.4564]
[46]
Küçükbay, H.; Gönül, Z.; Küçükbay, F.Z.; Tekin, Z.; Angeli, A.; Bartolucci, G.; Supuran, C.T.; Tatlıcı, E.; Apohan, E.; Yeşilada, Ö. Synthesis of new 7‐amino‐3,4‐dihydroquinolin‐2(1H)‐one‐peptide derivatives and their carbonic anhydrase enzyme inhibition, antioxidant, and cytotoxic activities. Arch. Pharm., 2021, 354(11), 2100122.
[http://dx.doi.org/10.1002/ardp.202100122]
[47]
Emamian, S.; Lu, T.; Kruse, H.; Emamian, H. Exploring nature and predicting strength of hydrogen bonds: A correlation analysis between atoms‐in‐molecules descriptors, binding energies, and energy components of symmetry‐adapted perturbation theory. J. Comput. Chem., 2019, 40(32), 2868-2881.
[http://dx.doi.org/10.1002/jcc.26068] [PMID: 31518004]
[48]
Deswal, Y.; Asija, S.; Kumar, D.; Jindal, D.K.; Chandan, G.; Panwar, V.; Saroya, S.; Kumar, N. Transition metal complexes of triazole-based bioactive ligands: Synthesis, spectral characterization, antimicrobial, anticancer and molecular docking studies. Res. Chem. Intermed., 2022, 48(2), 703-729.
[http://dx.doi.org/10.1007/s11164-021-04621-5]
[49]
Pettersen, E.F.; Goddard, T.D.; Huang, C.C.; Meng, E.C.; Couch, G.S.; Croll, T.I.; Morris, J.H.; Ferrin, T.E. UCSF CHIMERAX: Structure visualization for researchers, educators, and developers. Protein Sci., 2021, 30(1), 70-82.
[http://dx.doi.org/10.1002/pro.3943] [PMID: 32881101]
[50]
Marvin, S. ChemAxon. 2019. Available from: https://docs.chemaxon.com/display/docs/marvin-js-history-of-changes.md#aug-5th-2019-marvin-js19190
[51]
Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2010, 31(2), 455-461.
[http://dx.doi.org/10.1002/jcc.21334] [PMID: 19499576]
[52]
Dassault Systèmes. Discovery Studio Visualizer v17.2.0.16349; BIOVIA, 2016.
[53]
Stewart, J.J.; James, J.P. Mopac2016; Stewart Computational Chemistry: Colorado Springs, CO, USA, 2016, p. 650.
[54]
Alex, A.G. Firefly version 8.2.0, build number 10203, Copyright (c) 1994; Firefly Project: Moscow, Russia, 2016.
[55]
Lu, T.; Chen, F. Multiwfn: A multifunctional wavefunction analyzer. J. Comput. Chem., 2012, 33(5), 580-592.
[http://dx.doi.org/10.1002/jcc.22885] [PMID: 22162017]

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