Generic placeholder image

Anti-Infective Agents

Editor-in-Chief

ISSN (Print): 2211-3525
ISSN (Online): 2211-3533

Research Article

Design, Synthesis, and Pharmacological Evaluation of Substituted Oxadiazole-Pyridazin-3-One Derivatives as Antioxidant and Antimicrobial Agents

Author(s): Minaxi Saini, Rina Das* and Dinesh K. Mehta*

Volume 20, Issue 4, 2022

Published on: 05 July, 2022

Article ID: e170322202325 Pages: 10

DOI: 10.2174/2211352520666220317142519

Price: $65

Abstract

Background: The chemical modification of pyridazinone leads to a potent therapeutic agent.

Aims: A series of novel analogues of 4,5-dichloro-6-(substituted-benzyl)-2-(5-mercapto-[1,3,4]- oxadiazol-2-ylmethyl)-2H-pyridazin-3-one have been synthesized.

Objectives: The novel synthesized pyridazinone derivatives were docked for possible targets, followed by antimicrobial and antioxidant activities.

Methods: The target compounds were synthesized using a nucleophilic substitution reaction. The structures of newly synthesized compounds were confirmed by FT-IR, 1H-NMR, 13C-NMR, mass spectroscopy, and elemental analysis.

Results: The novel synthesised compounds were screened for their antimicrobial and antioxidant properties in vitro. Compound 5e showed good antibacterial and antifungal activity with MIC 25 μg/mL and 6.25 μg/mL against all the bacterial and fungal strains and in-vitro antioxidant activity with an IC50 of 51.64. The experimental results were further supported by molecular docking analysis using V-Life Science MDS 4.6 software and the GRIP batch docking method.

Conclusion: All the compounds have been evaluated in vitro for antioxidant and antimicrobial activities against several strains of microbes and have shown significant activity. The experimental results were further supported by molecular docking analysis, describing improved interaction patterns.

Keywords: Antimicrobial activity, antioxidant activity, oxadiazole, pyridazinone, docking, V-life Science MDS 4.6 software.

Graphical Abstract

[1]
Saini, M.; Mehta, D.K.; Das, R. Biological evaluation and molecular docking studies of synthesized 5-substituted-2-chlorophenyl-4-chloro derivatives bearing pyridazinone moiety. Lett. Org. Chem., 2020, 17(3), 170-183.
[http://dx.doi.org/10.2174/1570178616666190705152605]
[2]
Khaidem, S.; Sarveswari, S.; Gupta, R.; Vijayakumar, V. Synthesis and biological evaluation of some pyridazinone derivatives. Int. J. Res. Pharm. Chem., 2012, 2(2), 2231-2781.
[3]
Saini, M.; Mehta, D.K.; Das, R. Antimicrobial and antioxidant evaluation of some novel synthesized pyridazinone derivatives. IJPR, 2016, 8(4), 53-59.
[4]
Unsal, O.; Balkan, A.; Aypak, C.; Terzolu, B.; Goren, M.Z. Synthesis and evaluation of the anticonvulsant activities of some 5-(4-substitutedbenzylidene)-6-methyl-4,5-dihydropyridazine-3(2H)-ones. J. Pharm. Sci., 2004, (29), 185-194.
[5]
Ahmed, E.M.; Kassab, A.E.; El-Malah, A.A.; Hassan, M.S. Synthesis and biological evaluation of pyridazinone derivatives as selective COX-2 inhibitors and potential anti-inflammatory agents. Eur. J. Med. Chem., 2019, 171, 25-37.
[http://dx.doi.org/10.1016/j.ejmech.2019.03.036] [PMID: 30904755]
[6]
Saini, M.; Mehta, D.K.; Das, R. Pyridazinone derivatives as anti-inflammatory agents. Mini Rev. Med. Chem., 2016, 16(12), 996-1012.
[http://dx.doi.org/10.2174/1389557516666160611015815] [PMID: 27290912]
[7]
Husain, A.; Ahmad, A.; Bhandari, A.; Ram, V. Synthesis and antitubercular activity of pyridazinone derivatives. J. Chil. Chem. Soc., 2011, 56(3), 778-780.
[http://dx.doi.org/10.4067/S0717-97072011000300013]
[8]
Banerjee, P.S.; Sharma, P.K.; Nema, R.K. Synthesis and anticonvulsant activity of pyridazinone derivatives. Int. J. Chemtech Res., 2009, 1(3), 522-525.
[9]
Rathish, I.G.; Javed, K.; Ahmad, S.; Bano, S.; Alam, M.S.; Akhter, M.; Pillai, K.K.; Ovais, S.; Samim, M. Synthesis and evaluation of anticancer activity of some novel 6-aryl-2-(p-sulfamylphenyl)-pyridazin-3(2H)-ones. Eur. J. Med. Chem., 2012, 49(49), 304-309.
[http://dx.doi.org/10.1016/j.ejmech.2012.01.026] [PMID: 22305543]
[10]
Dogruer, D.S.; Onkol, T.; Ozkan, S.; Ozgen, S.; Sahin, M.F. Synthesis and antimicrobial activity of some 3(2H)-pyridazinone and 1(2H)-phthalazinone derivatives. Turk. J. Chem., 2008, (32), 469-479.
[11]
Cao, S.; Wei, N.; Zhao, C.; Li, L.; Huang, Q.; Qian, X. Syntheses, antifeedant activity, and QSAR analysis of new oxa(thia)diazolyl 3(2H)-pyridazinones. J. Agric. Food Chem., 2005, 53(8), 3120-3125.
[http://dx.doi.org/10.1021/jf047985e] [PMID: 15826068]
[12]
Asif, M. General Study of pyridazine compounds against cyclooxygenase enzyme and their relation with analgesic, anti-inflammatory and anti-arthritic activities. Chron. Young Sci., 2010, 1(3), 3-9.
[13]
Samanta, K.C.; Asif, M.; Pooja Garg, V.; Sharma, P.; Singh, R. Synthesis of different substituted pyridazinone derivatives and their anticonvulsant activity. Eur. J. Chem., 2011, 8(1), 245-251.
[14]
Dinoiu, V. Synthesis of new CF3-containing pyridazinone and lactam derivatives. Rev. Roum. Chim., 2006, 51(7-8), 623-628.
[15]
Piaz, V.D.; Vergelli, C.; Giovannoni, M.P.; Biancalani, C.; Cilibrizzi, A.; Graziano, A.; Cesari, N. Synthesis and evaluation of novel pyrrolo[2,3-d] and thieno[2,3-d]pyridazinones as in vitro antiproliferative agents. Acta Chim. Slov., 2009, (56), 571-579.
[16]
Cao, W.; Zhang, H.; Chen, J.; Deng, H.; Shao, M.; Lei, L.; Qian, J.; Zhu, Y.A. Facile preparation of trans-1,2-cyclopropanes containing trifluoro methyl phenyl group and its application to the construction of pyrazole and cyclopropane ring fused pyridazinone derivatives. Tetrahedron, 2008, 64(28), 6670-6674.
[http://dx.doi.org/10.1016/j.tet.2008.05.016]
[17]
Sotelo, E.; Coelho, A.; Ravina, E. Pyridazines. Part 34: Retro-eneassisted palladium-catalyzed, synthesis of 4,5-disubstituted-3(2H)- pyridazinones. Tetrahedron Lett., 2003, 44(24), 4459-4462.
[http://dx.doi.org/10.1016/S0040-4039(03)01029-3]
[18]
Asif, M. Anticonvulsant and comparative structure activity relationship of pyridazine derivatives with currently clinically used anticonvulsants. Int. J. Adv. Sci. Res., 2010, 1(1), 35-45.
[19]
Asif, M. Recent efforts for the development of antitubercular drug containing diazine ring. Med. Chem., 2012, 2(7), 151-167.
[20]
Asif, M.; Singh, A.; Ratnakar, L. Antimicrobial agents: Brief study of pyridazine derivatives against some phathogenic microrganisms. J. Pharm. Res., 2011, 4(3), 664-667.
[21]
Ames, B.N.; Shigenaga, M.K.; Hagen, T.M. Oxidants, antioxidants, and the degenerative diseases of aging. Proc. Natl. Acad. Sci. , 1993, 90(17), 7915-7922.
[http://dx.doi.org/10.1073/pnas.90.17.7915] [PMID: 8367443]
[22]
Costa, D.; Gomes, A.; Lima, J.L.; Fernandes, E. Singlet oxygen scavenging activity of non-steroidal anti-inflammatory drugs. Redox, 2008, 13(4), 153-160.
[http://dx.doi.org/10.1179/135100008X308876] [PMID: 18647485]
[23]
Caliskan-Ergün, B.; Süküroğlu, M.; Coban, T.; Banoğlu, E.; Suzen, S. Screening and evaluation of antioxidant activity of some pyridazine derivatives. J. Enzyme Inhib. Med. Chem., 2008, 23(2), 225-229.
[http://dx.doi.org/10.1080/14756360701475167] [PMID: 18343908]
[24]
Peksel, A.; Celik, C.; Ocal, N.; Yanardag, R. Antioxidant and radical scavenging activities of some norcantharidin and bridged perhydroisoindole derivatives. J. Serb. Chem. Soc., 2013, 78(1), 15-25.
[http://dx.doi.org/10.2298/JSC120123036P]
[25]
De, S.; Adhikari, S.; Tilak-Jain, J.; Menon, V.P.; Devasagayam, T.P. Antioxidant activity of an aminothiazole compound: Possible mechanisms. Chem. Biol. Interact., 2008, 173(3), 215-223.
[http://dx.doi.org/10.1016/j.cbi.2008.03.011] [PMID: 18466888]
[26]
Al-Ayed, A.S.; Hamdi, N. A new and efficient method for the synthesis of novel 3-acetyl coumarins oxadiazoles derivatives with expected biological activity. Molecules, 2014, 19(1), 911-924.
[http://dx.doi.org/10.3390/molecules19010911] [PMID: 24424404]
[27]
Suree, N.; Yi, S.W.; Thieu, W.; Marohn, M.; Damoiseaux, R.; Chan, A.; Jung, M.E.; Clubb, R.T. Discovery and structure-activity relationship analysis of Staphylococcus aureus sortase A inhibitors. Bioorg. Med. Chem., 2009, 17(20), 7174-7185.
[http://dx.doi.org/10.1016/j.bmc.2009.08.067] [PMID: 19781950]
[28]
El-Hashash, M.A.; Rizk, S.A. Synthesis of novel antibacterial and antifungal α-amino acids and heterocyclic compounds. Eur. Chem. Bull., 2013, 2, 637-641.
[29]
Kus, C.; Ayhan-Kılcıgil, G.; Tunçbilek, M.; Altanlar, N.; Çoban, T.; Can-Eke, B.; Iscan, M. Antimicrobial and antioxidant activities of some benzimidazole derivatives. Lett. Drug Des. Discov., 2009, 6(5), 374-379.
[http://dx.doi.org/10.2174/1570180810906050374]
[30]
Nayak, P.S.; Narayana, B.; Sarojini, B.K.; Sheik, S.; Shashidhara, K.S.; Chandrashekar, K.R. Design, synthesis, molecular docking and biological evaluation of imides, pyridazines, imidazoles derived from itaconic anhydride for potential antioxidant and antimicrobial activities. J. Taibah Univ. Sci., 2016, 10(6), 823-838.
[http://dx.doi.org/10.1016/j.jtusci.2014.09.005]
[31]
Mehta, D.K.; Taya, P.; Das, R.; Dua, K. Design, synthesis and molecular docking studies of novel thiadiazole analogues with potential antimicrobial and antiinflammatory activities. Antiinflamm. Antiallergy Agents Med. Chem., 2019, 18(2), 91-109.
[http://dx.doi.org/10.2174/1871520619666190307162442] [PMID: 30848217]
[32]
Mabkhot, Y.N.; Al-Har, M.S.; Barakat, A.; Aldawsari, F.D.; Aldalbahi, A.; Ul-Haq, Z. Synthesis, anti-microbial and molecular docking studies of quinazolin-4(3H)-one derivatives. Molecules, 2014, 19(7), 8725-8739.
[http://dx.doi.org/10.3390/molecules19078725] [PMID: 24968329]
[33]
Mowry, D.T. Mucochloric acid. II. Reactions of aldehyde group. J. Am. Chem. Soc., 1953, 75(8), 1909-1910.
[http://dx.doi.org/10.1021/ja01104a038]
[34]
Siddiqui, A.A.; Islam, M.; Kumar, S. Synthesis and antituberculostic activity of 5-{3′-oxo-6′-(substituted phenyl)-2′,3′,4′,5′-tetrahydropyridazin-2′-yl}methyl-2-substituted 1,3,4-oxadiazole. Pharm. Lett., 2010, 2(2), 319-327.
[35]
Yassin, F.A.; Seleim, A.F. Synthesis and reactions of 5-phenylpyrido-[3,2-d]-pyridazin-8(7H)-one derivatives. Pharma Chem., 2013, 5(3), 1-7.
[36]
Zou, X.J.; Zhang, Z.; Jin, G. Synthesis and biological activity of 1,3,4-oxadiazolesubstituted pyridazinones. J. Chem. Res., 2002, 2002(5), 228-230.
[http://dx.doi.org/10.3184/030823402103171780]
[37]
Zarrok, H.; Saddik, R.; Oudda, H.; Hammouti, B.; El Midaoui, A.; Zarrouk, A.; Benchat, N.; Touhami, N.E. 5-(2-Chlorobenzyl)-2,6-dimethylpyridazin-3-one: An efficient inhibitor of C38 steel corrosion in hydrochloric acid. Pharma Chem., 2011, 3(5), 272-282.
[38]
Islam, M.; Albratty, M. Antiviral activity of some novel synthesized 1, 3, 4-oxadiazole. J. Chem. Biol. Phys. Sci., 2016, 6(2), 624-633.
[39]
Morsy, J.M. Facile synthesis of 3(2H)-pyridazinones and 2(3H)-furanones of anticipated biological activities. J. Chin. Chem. Soc. , 2008, 55, 1243-1250.
[40]
Wu, J.; Song, B.; Chen, H.; Bhadury, P.; Hu, D. Synthesis and antifungal activity of 5-chloro-6-phenylpyridazin-3(2H)-one derivatives. Molecules, 2009, 14(9), 3676-3687.
[http://dx.doi.org/10.3390/molecules14093676] [PMID: 19783950]
[41]
Blake, J.S.; Dahl, M.V.; Herron, M.J.; Nelson, R.D. An immunoinhibitory cell wall glycoprotein (mannan) from Trichophyton rubrum. J. Invest. Dermatol., 1991, 96(5), 657-661.
[http://dx.doi.org/10.1111/1523-1747.ep12470582] [PMID: 2022872]
[42]
Singh, N.; Ranjana, R.; Kumari, M.; Kumar, B. A review on biological activities of hydrazone derivatives. Int. J. Pharm. Clin. Res., 2016, 8(3), 162-166.
[43]
Cristiane, F.F.G.; Alexandre, K.; Luciana, M.K. In vitro study of antioxidant and scavenger properties of phenolic compounds from Lychnophora species. Quim. Nova, 2010, 33(4), 867-870.
[44]
Alp, A.S.; Kilcigi̇l, G.; Özdamar, E.D.; Çoban, T.; Eke, B. Synthesis and evaluation of antioxidant activities of novel 1,3,4-oxadiazole and imine containing 1H-benzimidazoles. Turk. J. Chem., 2015, 39(1), 42-53.
[http://dx.doi.org/10.3906/kim-1403-44]
[45]
Sudha, R.; Charles, C.K.; Nithya, G. In vitro antioxidant activity of different substituted benzilic acid using 2,2-diphenyl-1-picryl hydrazyl radical, Abts assay method. Asian J. Pharm. Clin. Res., 2016, 9(3), 127-130.
[46]
Zou, X.J.; Lai, L.H.; Jin, G.Y.; Zhang, Z.X. Synthesis, fungicidal activity, and 3D-QSAR of pyridazinone-substituted 1,3,4-oxadiazoles and 1,3,4-thiadiazoles. J. Agric. Food Chem., 2002, 50(13), 3757-3760.
[http://dx.doi.org/10.1021/jf0201677] [PMID: 12059155]
[47]
Mehta, D.K.; Saini, M. Design, synthesis, molecular docking studies and biological evaluation of novel pyridazin-3-one derivatives. Int. J. Pharm. Biol. Sci., 2019, 10(1), 127-140.
[http://dx.doi.org/10.22376/ijpbs.2019.10.1.p127-140]
[48]
Khokra, S.L.; Khan, S.A.; Thakur, P.; Chowdhary, D.; Ahmad, A.; Husain, A. Synthesis, molecular docking and potential antioxidant activity of di/trisubstituted pyridazinone derivatives. J. Chin. Chem. Soc. , 2016, 63(9), 739-750.
[http://dx.doi.org/10.1002/jccs.201600051]
[49]
Shehzadi, N.; Hussain, K.; Khan, M.T.; Bukhari, N.I.; Islam, M.; Salman, M.; Siddiqui, S.Z.; Rehman, A.; Abbasi, M.A. Radical scavenging and endogenous defence system inducing activities of 5-[(4-chlorophenoxy)methyl]- 1,3,4-oxadiazole-2-thiol: A Novel Antioxidant. Indian J. Pharm. Sci., 2018, 80(6), 1125-1135.
[http://dx.doi.org/10.4172/pharmaceutical-sciences.1000464]
[50]
Nagle, P.; Pawar, Y.; Sonawane, A.; Bhosale, S.; More, D. Docking simulation, synthesis and biological evaluation of novel pyridazinone containing thymol as potential antimicrobial agents. Med. Chem. Res., 2014, 23(2), 918-926.
[http://dx.doi.org/10.1007/s00044-013-0685-2]
[51]
Ozdemir, Z.; Alagoz, M.A.; Akdemir, A.G.; Ozcelik, A.B.; Ozcelik, B.; Uysal, M. Studies on a novel series of 3(2H)-pyridazinones: Synthesis, molecular modelling, antimicrobial activity. J. Res. Pharm., 2019, 23(5), 960-972.
[http://dx.doi.org/10.35333/jrp.2019.43]
[52]
Devgun, M.; Prasad, S.; Khokra, S.L.; Narang, R. Molecular docking studies of dihydropyridazin-3(2H)-one derivatives as Antifungal, antibacterial and anti-helmintic agents. World J. Adv. Res. Rev., 2021, 12(01), 186-214.

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy