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Current Drug Discovery Technologies

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ISSN (Print): 1570-1638
ISSN (Online): 1875-6220

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Research Article

Synthesis and Biological Activity Evaluation of Pyrazole–1,2,4–triazole Hybrids: A Computer-aided Docking Studies

Author(s): Naga Mohan Mallisetty*, Hanumantharao Ganipisetti, Debendra Majhi, Raju Sirisilla and Venkata Nagendra Kumar Putta*

Volume 20, Issue 2, 2023

Published on: 28 December, 2022

Article ID: e251122211263 Pages: 12

DOI: 10.2174/1570163820666221125121625

Price: $65

Abstract

Background: In the present study, a new series of 1,2,4-triazole linked to pyrazole derivatives (8a-j) of 4-(((7-amino-7H-[1,2,4]triazolo[4,3-b][1,2,4]triazol-6-yl)methyl)amino)-1,5-dimethyl- 2-phenyl-1H-pyrazol-3(2H)-one were synthesized and assessed for their antibacterial and anticancer activity.

Objective: Encouraged by these results, these analogues 4-(((7-amino-7H-[1,2,4]triazolo[4,3- b][1,2,4]triazol-6-yl)methyl)amino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-ones 8 have been synthesized and their inhibitory potential activity against different bacterial microorganisms and cancer cell lines was discussed.

Methods: All the synthesized final scaffolds were characterized by 1H NMR, 13C NMR, IR, mass and elemental analysis. All the synthesized 1,2,4–triazole linked to pyrazole compounds were evaluated for their antimicrobial sensitivity by using the agar dilution technique. The anticancer activity of these compounds has been assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay and docking results are described by Autodock 4.2.

Results: In vitro analysis suggests that compounds 8h, 8f, and 8b demonstrated excellent antibacterial activity against S. aureus, P. aeruginosa, S. epidermidis with MICs of 8, 8, 11 μg/mL respectively, while the remaining compounds showed moderate to good inhibitory potential. Some of them exhibited potent cytotoxicity against MCF-7 and P388 cancer cell lines and compounds 8c, 8f, and 8d reveal the highest potency against MCF-7 with IC50 values 2.8 ± 0.4, 3.1 ± 0.4, 3.5 ± 0.2 μM, respectively. Especially 8c, 8i and 8f showed better interaction patterns with amino acids Ala197 (N–N), Lys168 (N–N), Asn163 (O–N) at 3.13, 3.09, 3.00 A° as reported in DNA (Topo II) complex (1ZXM).

Conclusion: New findings have established the fact that fused 1,2,4-triazoles linked to pyrazole contributed great significance in the field of medicinal chemistry due to their various biological properties.

Graphical Abstract

[1]
a) Klapötke TM, Stierstorfer J. Azidoformamidinium and 5-aminotetrazolium dinitramide-two highly energetic isomers with a balanced oxygen content. Dalton Trans 2009; 4(4): 643-53.
[http://dx.doi.org/10.1039/B811767E] [PMID: 19378557];
b) Klapötke TM, Sabaté CM, Stierstorfer J. Neutral 5-nitrotetrazoles: Easy initiation with low pollution. New J Chem 2009; 33(1): 136-47.
[http://dx.doi.org/10.1039/B812529E];
c) Thottempudi V, Shreeve JM. Synthesis and promising properties of a new family of high-density energetic salts of 5-nitro-3-trinitromethyl-1H-1,2,4-triazole and 5,5′-bis(trinitromethyl)-3,3′-azo-1H-1,2,4-triazole. J Am Chem Soc 2011; 133(49): 19982-92.
[http://dx.doi.org/10.1021/ja208990z] [PMID: 22029279];
d) Thottempudi V, Gao H, Shreeve JM. Trinitromethyl-substituted 5-nitro- or 3-azo-1,2,4-triazoles: Synthesis, characterization, and energetic properties. J Am Chem Soc 2011; 133(16): 6464-71.
[http://dx.doi.org/10.1021/ja2013455] [PMID: 21449560]
[2]
Gao H, Shreeve JM. Azole-based energetic salts. Chem Rev 2011; 111(11): 7377-436.
[http://dx.doi.org/10.1021/cr200039c] [PMID: 21838230]
[3]
Kohler J, Mayer R. Explosivstoffe. (9th ed.), Weinheim: Wiley VCH 1998.
[http://dx.doi.org/10.1002/9783527625826]
[4]
Oga S. Method for producing bitrazole amine compound. JP Patent 2006249061, 2006.
[5]
Klapotke TM, Holl G, Geith J, Hammerl A, Weigand JJ. New trends in research of energetic materials. Proceedings of the Seminar. 7th. Pardubice, Czech Republic, ed. J. Wagenknecht, Press of the University of Pardubice, Pardubice, 2004; 25, 100.
[6]
a) Klapötke TM, Stierstorfer J, Wallek AU. Nitrogen-rich salts of 1-methyl-5-nitriminotetrazolate: an auspicious class of thermally stable energetic materials. Chem Mater 2008; 20(13): 4519-30.
[http://dx.doi.org/10.1021/cm8004166];
b) Srinivas D, Ghule VD, Muralidharan K, Jenkins HDB. Tetraanionic nitrogen-rich tetrazole-based energetic salts. Chem Asian J 2013; 8(5): 1023-8.
[http://dx.doi.org/10.1002/asia.201300033] [PMID: 23418032]
[7]
Karrouchi K, Radi S, Ramli Y, et al. Synthesis and pharmacological activities of pyrazole derivatives: A review. Molecules 2018; 23(1): 134.
[http://dx.doi.org/10.3390/molecules23010134] [PMID: 29329257]
[8]
Nossier E, Fahmy H, Khalifa N, El-Eraky W, Baset M. Design and synthesis of novel pyrazole-substituted different nitrogenous hetero-cyclic ring systems as potential anti-inflammatory agents. Molecules 2017; 22(4): 512.
[http://dx.doi.org/10.3390/molecules22040512] [PMID: 28338602]
[9]
Vijesh AM, Isloor AM, Shetty P, Sundershan S, Fun HK. New pyrazole derivatives containing 1,2,4-triazoles and benzoxazoles as potent antimicrobial and analgesic agents. Eur J Med Chem 2013; 62: 410-5.
[http://dx.doi.org/10.1016/j.ejmech.2012.12.057] [PMID: 23385092]
[10]
Jia H, Bai F, Liu N, et al. Design, synthesis and evaluation of pyrazole derivatives as non-nucleoside hepatitis B virus inhibitors. Eur J Med Chem 2016; 123: 202-10.
[http://dx.doi.org/10.1016/j.ejmech.2016.07.048] [PMID: 27484509]
[11]
Zhou L, Wang PY, Zhou J, et al. Antimicrobial activities of pyridinium-tailored pyrazoles bearing 1,3,4-oxadiazole scaffolds. J Saudi Chem Soc 2017; 21(7): 852-60.
[http://dx.doi.org/10.1016/j.jscs.2017.04.005]
[12]
Sayed GH, Azab ME, Anwer KE, Raouf MA, Negm NA. Pyrazole, pyrazolone and enaminonitrile pyrazole derivatives: Synthesis, characterization and potential in corrosion inhibition and antimicrobial applications. J Mol Liq 2018; 252: 329-38.
[http://dx.doi.org/10.1016/j.molliq.2017.12.156]
[13]
Wang M, Xu S, Lei H, et al. Design, synthesis and antitumor activity of Novel Sorafenib derivatives bearing pyrazole scaffold. Bioorg Med Chem 2017; 25(20): 5754-63.
[http://dx.doi.org/10.1016/j.bmc.2017.09.003] [PMID: 28927801]
[14]
Özdemir Z, Karakurt A, Calis U, et al. Synthesis, anticonvulsant and antimicrobial activities of some new [1-(2-naphthyl)-2-(pyrazol-1-yl)ethanone]oxime ethers. Med Chem 2014; 11(1): 41-9.
[http://dx.doi.org/10.2174/1573406410666140428150358] [PMID: 24773349]
[15]
Karrouchi K, Chemlal L, Taoufik J, et al. Synthesis, antioxidant and analgesic activities of Schiff bases of 4-amino-1,2,4-triazole derivatives containing a pyrazole moiety. Ann Pharm Fr 2016; 74(6): 431-8.
[http://dx.doi.org/10.1016/j.pharma.2016.03.005] [PMID: 27107461]
[16]
Chae E, Shin YJ, Ryu EJ, et al. Discovery of biological evaluation of pyrazole/imidazole amides as mGlu5 receptor negative allosteric modulators. Bioorg Med Chem Lett 2013; 23(7): 2134-9.
[http://dx.doi.org/10.1016/j.bmcl.2013.01.116] [PMID: 23434029]
[17]
Malvar DC, Ferreira RT, de Castro RA, et al. Antinociceptive, anti-inflammatory and antipyretic effects of 1.5-diphenyl-1H-Pyrazole-3-carbohydrazide, a new heterocyclic pyrazole derivative. Life Sci 2014; 95(2): 81-8.
[http://dx.doi.org/10.1016/j.lfs.2013.12.005] [PMID: 24355293]
[18]
Li W, Li J, Shen H, Cheng J, Li Z, Xu X. Synthesis, nematicidal activity and docking study of novel chromone derivatives containing substituted pyrazole. Chin Chem Lett 2017; 29(6): 911-4.
[19]
Karrouchi K, Yousfi E, Sebbar N, et al. New pyrazole-hydrazone derivatives: X-ray analysis, molecular structure investigation via Density Functional Theory (DFT) and their high in-situ catecholase activity. Int J Mol Sci 2017; 18(11): 2215.
[http://dx.doi.org/10.3390/ijms18112215] [PMID: 29068421]
[20]
Wang SL, Shi YJ, He HB, Li Y, Li Y, Dai H. Synthesis and bioactivity of novel pyrazole oxime derivatives containing oxazole ring. Chin Chem Lett 2015; 26(6): 672-4.
[http://dx.doi.org/10.1016/j.cclet.2015.04.017]
[21]
Hernandez-Vazquez E, Ocampo-Montalban H, Ceron-Romero L, et al. Antidiabetic, anti-dyslipidemic and toxicity profile of ENV-2: A potent pyrazole derivative against diabetes and related diseases. Eur J Pharmacol 2017; 803: 159.
[http://dx.doi.org/10.1016/j.ejphar.2017.03.036] [PMID: 28322830]
[22]
Aouad MR, Mayaba MM, Naqvi A, et al. Design, synthesis, in silico and in vitro antimicrobial screenings of novel 1,2,4-triazoles carrying 1,2,3-triazole scaffold with lipophilic side chain tether. Chem Cent J 2017; 11(1): 117.
[http://dx.doi.org/10.1186/s13065-017-0347-4] [PMID: 29159721]
[23]
Ünver Y, Deniz S, Çelik F, Akar Z, Küçük M, Sancak K. Synthesis of new 1,2,4-triazole compounds containing Schiff and Mannich bases (morpholine) with antioxidant and antimicrobial activities. J Enzyme Inhib Med Chem 2016; 31(S3): 89-95.
[http://dx.doi.org/10.1080/14756366.2016.1206088] [PMID: 27430189]
[24]
Swamy DK, Kuberkar SV, Deshmukh MV. Studies on synthesis, antibacterial screening and the mass fragmentation of 1-(4,6-dimethylbenzothiazolyl)-3,5-disubstituted-1,2,4-1H-triazoles. J Chem Chem Pharmaceut Res 2010; 2: 411.
[25]
Gupta D, Jain DK. Synthesis, antifungal and antibacterial activity of novel 1,2,4-triazole derivatives. J Adv Pharm Technol Res 2015; 6(3): 141-6.
[http://dx.doi.org/10.4103/2231-4040.161515] [PMID: 26317080]
[26]
Ming-Xia Song M-X, Deng X-Q. Recent developments on triazole nucleus in anticonvulsant compounds: A review. J Enzyme Inhib Med Chem 2018; 33(1): 453-78.
[27]
Mohammad A. A brief review on antitubercular activity of pharmacological active some triazole analogues Glob J Res Rev 2014; 1: 051.
[28]
Bawa S, Ali R, Afzal O, et al. Antidepressant potential of nitrogen-containing heterocyclic moieties: An updated review. J Pharm Bioallied Sci 2011; 3(2): 194-212.
[http://dx.doi.org/10.4103/0975-7406.80765] [PMID: 21687347]
[29]
El-Gazzar YI, Georgey HH, El-Messery SM, et al. Synthesis, biological evaluation and molecular modeling study of new (1,2,4-triazole or 1,3,4-thiadiazole)-methylthio-derivatives of quinazolin-4(3 H)-one as DHFR inhibitors. Bioorg Chem 2017; 72: 282-92.
[http://dx.doi.org/10.1016/j.bioorg.2017.04.019] [PMID: 28499189]
[30]
Patel BD, Bhadada SV, Ghate MD. Design, synthesis and anti-diabetic activity of triazolotriazine derivatives as dipeptidyl peptidase-4 (DPP-4) inhibitors. Bioorg Chem 2017; 72: 345-58.
[http://dx.doi.org/10.1016/j.bioorg.2017.03.004] [PMID: 28302310]
[31]
Saeedi M, Safavi M, Karimpour-Razkenari E, et al. Synthesis of novel chromenones linked to 1,2,3-triazole ring system: Investigation of biological activities against Alzheimer’s disease. Bioorg Chem 2017; 70: 86-93.
[http://dx.doi.org/10.1016/j.bioorg.2016.11.011] [PMID: 27914694]
[32]
Le Duc Y, Licsandru E, Vullo D, Barboiu M, Supuran CT. Carbonic anhydrases activation with 3-amino-1H-1,2,4-triazole-1-carboxamides: Discovery of subnanomolar isoform II activators. Bioorg Med Chem 2017; 25(5): 1681-6.
[http://dx.doi.org/10.1016/j.bmc.2017.01.031] [PMID: 28161251]
[33]
Demirbas N, Ugurluo Glu R. Synthesis of novel 4-alkylidene- and 4-alkylamino-5-oxo-4,5-dihydro-[1,2,4]triazole derivatives and investigation of their antitumor activities. Turk J Chem 2004; 28: 559.
[34]
Shivarama HB, Veerendra B, Shivananda MK, Poojary B. Synthesis characterization and anticancer activity studies on some Mannich bases derived from 1,2,4-triazoles. Eur J Med Chem 2003; 38(7-8): 759-67.
[http://dx.doi.org/10.1016/S0223-5234(03)00128-4] [PMID: 12932907]
[35]
Kaushik CP, Lal K, Kumar A, Kumar S. Synthesis and biological evaluation of amino acid-linked 1,2,3-bistriazole conjugates as poten-tial antimicrobial agents. Med Chem Res 2014; 23(6): 2995-3004.
[http://dx.doi.org/10.1007/s00044-013-0882-z]
[36]
Gerlier D, Thomasset N. Use of MTT colorimetric assay to measure cell activation. J Immunol Methods 1986; 94(1-2): 57-63.
[http://dx.doi.org/10.1016/0022-1759(86)90215-2] [PMID: 3782817]
[37]
Abu Bakar MF, Mohamad M, Rahmat A, Burr SA, Fry JR. Cytotoxicity, cell cycle arrest, and apoptosis in breast cancer cell lines exposed to an extract of the seed kernel of Mangifera pajang (bambangan). Food Chem Toxicol 2010; 48(6): 1688-97.
[http://dx.doi.org/10.1016/j.fct.2010.03.046] [PMID: 20363279]
[38]
ACD/Chem Sketch, version 2020.2.1, Advanced Chemistry Development, Inc., Toronto, ON, Canada. 2021. Available from: www.acdlabs.com
[39]
O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR. Open Babel: An open chemical toolbox. J Cheminform 2011; 3(1): 33.
[http://dx.doi.org/10.1186/1758-2946-3-33] [PMID: 21982300]
[40]
Morris GM, Huey R, Lindstrom W, et al. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem 2009; 30(16): 2785-91.
[http://dx.doi.org/10.1002/jcc.21256] [PMID: 19399780]
[41]
Morris GM, Goodsell DS, Halliday RS, et al. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem 1998; 19(14): 1639-62.
[http://dx.doi.org/10.1002/(SICI)1096-987X(19981115)19:14<1639:AID-JCC10>3.0.CO;2-B]
[42]
Wang R, Lu Y, Wang S. Comparative evaluation of 11 scoring functions for molecular docking. J Med Chem 2003; 46(12): 2287-303.
[http://dx.doi.org/10.1021/jm0203783] [PMID: 12773034]

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