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Abstract

The growing pharmaceutical relevance of drug-resistant pathogens has necessitated the emergence of new treatment medicines. In this scenario, a novel series of N′-(substituted)-2-(4-(3-nitroimidazo[1,2-b]-pyridazin-6-yl)piperazin-1-yl)acetohydrazides and 1-(2-(substituted)-5-((4-(3-nitroimidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)methyl)-1,3,4-oxadiazol-3 (2H)-yl)ethan-1-ones have been synthesized and characterized by 1H & 13C NMR spectral data and screened for antimicrobial activity, as well as molecular docking studies. The synthesized compounds were tested against Escherichia coli (1668), Bacillus cereus (1272), Candida albicans (854) by using disc diffusion method. Among all the synthesized compounds 3c and 4c exhibit good potent antimicrobial activity against Escherichia coli, 3a, 4c against Bacillus cereus and 4a, 4c against Candida albicans. The Auto-Dock 4.2/ADT application was performed to investigate the binding interaction of the synthesized compounds with BAX protein. Among all the synthesized compounds 4e, 4a, 3e and 3a showed the highest binding affinity (-8.0, -7.5, -7.0 and -6.9 Kcal/mol) with BAX protein.

Keywords

3-Nitro-6-(piperazin-1-yl)imidazo[1 2-b]pyridazine Molecular docking 1 3 4-Oxadiazoles Antibacterial activity Antifungal activity BAX protein Hydrazones.

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Subba Rao, B., Sanjeeva, P., Karuna Raman, P., Satyanarayana Swamy, V., Kamala Prasad, V., & Venkata Ramana, P. (2022). Synthesis of N’-(Substituted)-2-(4-(3-nitroimidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)acetohydrazides and their 1,3,4-Oxadiazole Derivatives: Characterization, Antimicrobial Activity and Molecular Docking Studies. Asian Journal of Organic & Medicinal Chemistry, 7(2), 187–197. https://doi.org/10.14233/ajomc.2022.AJOMC-P384
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References

  1. M.Y. Freeman, M.Y. Lee, H. Lu, X. Wang and E. Rodriguez, 1-Thia-Cope Rearrangements during the Thionation of 2-endo-3-endo-Bis(aroyl)bicyclo[2.2.1]hept-5-enes, J. Org. Chem., 59, 3695 (1994); https://doi.org/10.1021/jo00092a034
  2. D. Sharma, Salahuddin, V. Sharma, R. Kumar, S. Joshi, S. Kumari, S. Saxena, A. Mazumder, M.S. Yar and M.J. Ahsan, 1,3,4-Oxadiazoles as Potential Pharmacophore for Cytotoxic Potentiality: A Comprehensive Review, Curr. Top. Med. Chem., 21, 1377 (2021); https://doi.org/10.2174/1568026621666210612031144
  3. J.R. Dimmock, S.C. Vashishtha and J.P. Stables, Anticonvulsant Properties of Various Acetylhydrazones, Oxamoylhydrazones and Semicarbazones Derived from Aromatic and Unsaturated Carbonyl Compounds, Eur. J. Med. Chem., 35, 241 (2000); https://doi.org/10.1016/S0223-5234(00)00123-9
  4. B.F.D. Gatphoh, N.N. Aggarwal, M.V. Kumar and B.C. Revanasiddappa, Synthesis, in silico Studies, and Anticonvulsant Activity of 1,3,4-Oxadiazole Derivatives, Trends Sci., 18, 701 (2021); https://doi.org/10.48048/tis.2021.701
  5. L. Kayukova, A. Vologzhanina, K. Praliyev, G. Dyusembaeva, A. Uzakova, G. Baitursynova, V. Bismilda, L. Chingissova and K. Akatan, Boulton-Katritzky Rearrangement of 5-Substituted Phenyl-3-[2-(morpholin-1-yl)ethyl]-1,2,4-oxadiazoles as a Synthetic Path to Spiropyrazoline Benzoates and Chloride with Antitubercular Properties, Molecules, 26, 967 (2021); https://doi.org/10.3390/molecules26040967
  6. R. Das and D.K. Mehta, Evaluation and Docking Study of Pyrazine Containing 1,3,4-Oxadiazoles Clubbed with Substituted Azetidin-2-one: A New Class of Potential Antimicrobial and Antitubercular, Drug Res., 71, 26 (2021); https://doi.org/10.1055/a-1252-2378
  7. H. Randhawa, A. Kamboj and A.K. Saluja, Synthesis, Pharmacological Evaluation and Computational Studies of Some Novel Hydrazone Derivatives of Thiophene Chalcone as Antimicrobial and Antioxidant Agents, World J. Pharm. Res., 3, 3146 (2014).
  8. I.F. Izgi, I.F. Sengul, E. Sahin, M.S. Koca, F. Cebeci and H. Kandemir, Synthesis of 7-Azaindole Based Carbohydrazides and 1,3,4-Oxadiazoles: Antioxidant Activity, a-Glucosidase Inhibition Properties and Docking Study, J. Mol. Struct., 1247, 131343 (2022); https://doi.org/10.1016/j.molstruc.2021.131343
  9. M. El-Behery and H. El-Twigry, Synthesis, Magnetic, Spectral and Antimicrobial Studies of Cu(II), Ni(II) Co(II), Fe(III), and UO2(II) Complexes of a New Schiff Base Hydrazone Derived from 7-Chloro-4-hydrazinoquinoline, Mol. Biomol., 66, 28 (2007); https://doi.org/10.1016/j.saa.2006.02.017
  10. M. Rabie, Two Antioxidant 2,5-Disubstituted-1,3,4-oxadiazoles (CoViTris2020 and ChloViD2020): Successful Repurposing Against COVID-19 as the First Potent Multitarget Anti-SARS-CoV-2 Drugs, New J. Chem., 45, 761 (2021); https://doi.org/10.1039/D0NJ03708G
  11. E. Kümmerle, J.M. Raimundo, C.M. Leal, G.S. da Silva, T.L. Balliano, M.A. Pereira, C.A. de Simone, R.T. Sudo, G. Zapata-Sudo and C.A. Fraga, Studies Towards the Identification of Putative Bioactive Conformation of Potent Vasodilator Arylidene N-Acylhydrazone Derivatives, Eur. J. Med. Chem., 44, 4004 (2009); https://doi.org/10.1016/j.ejmech.2009.04.044
  12. S. Nasr, S. Bondock and M. Youns, Anticancer Activity of New Coumarin Substituted Hydrazide–Hydrazone Derivatives, Eur. J. Med. Chem., 76, 539 (2014); https://doi.org/10.1016/j.ejmech.2014.02.026
  13. M.P. Tantak, M. Malik, L. Klingler, Z. Olson, A. Kumar, R. Sadana and D. Kumar, Indolyl-a-keto-1,3,4-oxadiazoles: Synthesis, Anti-Cell Proliferation Activity, and Inhibition of Tubulin Polymerization, Bioorg. Med. Chem. Lett., 37, 127842 (2021); https://doi.org/10.1016/j.bmcl.2021.127842
  14. N. Kandile, M. Mohamed, H. Zaky and H. Mohamed, Novel Pyridazine Derivatives: Synthesis and Antimicrobial Activity Evaluation, Eur. J. Med. Chem., 44, 1989 (2009); https://doi.org/10.1016/j.ejmech.2008.09.047
  15. N. Singh, R. Ranjana, M. Kumari and B. Kumar, A Review on Biological Activities of Hydrazone Derivatives, Int. J. Pharm. Clin. Res., 8, 162 (2016).
  16. M.G. Mamolo, V. Falagiani, D. Zampieri, L. Vio and E. Banfi, Synthesis and Antimycobacterial Activity of [5-(Pyridin-2-yl)-1,3,4-thiadiazol-2-ylthio]acetic Acid Arylidene-Hydrazide Derivatives, Il Farmaco, 56, 587 (2001); https://doi.org/10.1016/S0014-827X(01)01097-7
  17. K. Singh, R. Pal, S.A. Khan, B. Kumar and M.J. Akhtar, Insights into the Structure Activity Relationship of Nitrogen-Containing Heterocyclics for the Development of Antidepressant Compounds: An Updated Review, J. Mol. Struct., 1237, 130369 (2021); https://doi.org/10.1016/j.molstruc.2021.130369
  18. V. Singh, V. Srivastava, G. Palit and K. Shanker, Coumarin Congeners as Antidepressants, Arzneimittelforschung, 42, 993 (1992).
  19. G. Gemma, G. Kukreja, C. Fattorusso, M. Persico, M.P. Romano, M. Altarelli, L. Savini, G. Campiani, E. Fattorusso, N. Basilico, D. Taramelli, V. Yardley and S. Butini, Synthesis of N1-Arylidene-N2-quinolyl- and N2-Acrydinylhydrazones as Potent Antimalarial Agents Active Against CQ-Resistant P. falciparum Strains, Bioorg. Med. Chem. Lett., 16, 5384 (2006); https://doi.org/10.1016/j.bmcl.2006.07.060
  20. I.A. Darwish, T.A. Wani, N.Y. Khalil, A.-A. Al-Shaikh and N. Al-Morshadi, Development of a Novel 96-Microwell Assay with High Throughput for Determination of Olmesartan Medoxomil in its Tablets, Chem. Cent. J., 6, 1 (2012); https://doi.org/10.1186/1752-153X-6-1
  21. A. Patil and S. Mohite, Synthesis of 1,3,4-Oxadiazole Derivatives with its Antifungal Activity Evaluation, Asian J. Res. Chem, 14, 336 (2021); https://doi.org/10.52711/0974-4150.2021.00057
  22. M. Almasirad, M. Tajik, D. Bakhtiari, A. Shafiee, M. Abdollahi, M.J. Zamani, R. Khorasani and H. Esmaily, Synthesis and Analgesic Activity of N-Arylhydrazone Derivatives of Mefenamic Acid, J. Pharm. Pharm. Sci., 8, 419 (2005).
  23. K. Rana, Salahuddin and J.K. Sahu, Significance of 1,3,4-Oxadiazole Containing Compounds in New Drug Development, Curr. Drug Res. Rev., 13, 90 (2021); https://doi.org/10.2174/2589977512666201221162627
  24. W. Bispo Jr., M.S. Alexandre-Moreira, M.A. Alves, A. Perez-Rebolledo, G.L. Parrilha, E.E. Castellano, O.E. Piro, E.J. Barreiro, L.M. Lima and H. Beraldo, Analgesic and Anti-Inflammatory Activities of Salicylaldehyde 2-Chlorobenzoyl Hydrazone (H2LASSBio-466), Salicylaldehyde 4-Chlorobenzoyl Hydrazone (H2LASSBio-1064) and their Zinc(II) Complexes, Molecules, 16, 6902 (2011); https://doi.org/10.3390/molecules16086902
  25. R. Nesaragi, R.R. Kamble, S. Dixit, B. Kodasi, S.R. Hoolageri, P.K. Bayannavar, J.P. Dasappa, S. Vootla, S.D. Joshi and V.M. Kumbar, Green Synthesis of Therapeutically Active 1,3,4-Oxadiazoles as Antioxidants, Selective COX-2 Inhibitors and their in silico Studies, Bioorg. Med. Chem. Lett., 43, 128112 (2021); https://doi.org/10.1016/j.bmcl.2021.128112
  26. V.A. Shelke, S.M. Jadhav, S.G. Shankarwar, A.S. Munde and T.K. Chondhekar, Synthesis, Characterization, Antibacterial and Antifungal Studies of Some Transition and Rare Earth Metal Complexes of Nbenzylidene-2-hydroxybenzohydrazide, Bull. Chem. Soc. Ethiopia, 25, 381 (2011); https://doi.org/10.4314/bcse.v25i3.68590
  27. K. Ibrahim, I. Gabr and R. Zaky, Synthesis and Magnetic, Spectral and Thermal Eukaryotic DNA Studies of Some 2-Acetylpyridine-[N-(3-hydroxy-2-naphthoyl)]hydrazone Complexes, J. Coord. Chem., 62, 1100 (2009); https://doi.org/10.1080/00958970802464616
  28. P. Zoufalý, A. Kliuikov, E. Èižmár, I. Císaøová and R. Herchel, cis- and trans-Isomers of Fe(II) and Co(II) Complexes with Oxadiazole Derivatives - Structural and Magnetic Properties, Eur. J. Inorg. Chem., 2021, 1190 (2021); https://doi.org/10.1002/ejic.202001148
  29. O. Pouralimardan, A.-C. Chamayou, C. Janiak and H. Hosseini-Monfared, Hydrazone Schiff Base-Manganese(II) Complexes: Synthesis, Crystal Structure and Catalytic Reactivity, Inorg. Chim. Acta, 360, 1599 (2007); https://doi.org/10.1016/j.ica.2006.08.056
  30. S. Basu, S. Chowdhury, R. Banerjee, H.S. Evans and S. Mukherjee, A Novel Blue Luminescent High-Spin Iron(III) Complex with Interlayer O–H···Cl Bridging: Synthesis, Structure and Spectroscopic Studies, Polyhedron, 26, 3617 (2007); https://doi.org/10.1016/j.poly.2007.03.053
  31. O.V. Arapov, O.F. Alferova, E.I. Levocheskaia and I.I. Krasil’nikov, Radioprotective Efficiency of Acyl Hydrazones, Radiobiologiia, 27, 843 (1987).
  32. S. Siemann, D.P. Evanoff, L. Marrone, A.J. Clarke, T. Viswanatha and G.I. Dmitrienko, N-Arylsulfonyl Hydrazones as Inhibitors of IMP-1 Metallo-b-Lactamase, Antimicrob. Agents Chemother., 46, 2450 (2002); https://doi.org/10.1128/AAC.46.8.2450-2457.2002
  33. M. Bakir, O. Green and W.H. Mulder, Synthesis, Characterization and Molecular Sensing Behavior of [ZnCl2(h3-N,N,O-dpkbh)] (dpkbh = di-2-pyridyl ketone benzoyl hydrazone), J. Mol. Struct., 873, 17 (2008); https://doi.org/10.1016/j.molstruc.2007.03.001
  34. A. Lipinski, F. Lombardo, B.W. Dominy and P.J. Feeney, Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings, Adv. Drug Deliv. Rev., 23, 3 (1997); https://doi.org/10.1016/S0169-409X(96)00423-1
  35. W. Kahsai, K. Xiao, S. Rajagopal, S. Ahn, A.K. Shukla, J. Sun, T.G. Oas and R.J. Lefkowitz, Multiple Ligand-Specific Conformations of the b2-Adrenergic Receptor, Nat. Chem. Biol., 7, 692 (2011); https://doi.org/10.1038/nchembio.634
  36. X.-Y. Meng, H.-X. Zhang, M. Mezei and M. Cui, Molecular Docking: A Powerful Approach for Structure-based Drug Discovery, Curr. Comput. Aided Drug Des., 7, 146 (2011); https://doi.org/10.2174/157340911795677602
  37. F. Lopez-Vallejo, T. Caulfield, K. Martinez-Mayorga, M. A. Giulianotti, A. Nefzi, R. A. Houghten and J. L. Medina-Franco, Integrating Virtual Screening and Combinatorial Chemistry for Accelerated Drug Discovery, Comb. Chem. High Throughput Screen., 14, 475 (2011); https://doi.org/10.2174/138620711795767866
  38. S.-Y. Huang and X. Zou, Advances and Challenges in Protein-Ligand Docking, Int. J. Mol. Sci., 11, 3016 (2010); https://doi.org/10.3390/ijms11083016
  39. S. Cheemanapalli, A. C.M, S.B. Pakala and S.K. Chitta, Design and Screening of Syringic Acid Analogues as BAX Activators-An in silico Approach to Discover “BH3 Mimetics”, Comput. Biol. Chem., 74, 49 (2018); https://doi.org/10.1016/j.compbiolchem.2018.03.003
  40. Y. Tan, M.R. Demeter, H. Ruan and M.J. Comb, BAD Ser-155 Phosphorylation Regulates BAD/Bcl-XL Interaction and Cell Survival, J. Biol. Chem., 275, 25865 (2000); https://doi.org/10.1074/jbc.M004199200
  41. C. Mulakayala, B. Banaganapalli, N. Mulakayala, M. Pulaganti, A. C.M and S.K. Chitta, Design and Evaluation of New Chemotherapeutics of Aloe-Emodin (AE) against the Deadly Cancer Disease: An in silico Study, J. Chem. Biol., 6, 141 (2013); https://doi.org/10.1007/s12154-013-0097-2
  42. Q. Zheng, B. Wang, J. Gao, N. Xin, W. Wang, X. Song, Y. Shao and C. Zhao, CD155 Knockdown Promotes Apoptosis via AKT/Bcl-2/Bax In Colon Cancer Cells, J. Cell. Mol. Med., 22, 131 (2018); https://doi.org/10.1111/jcmm.13301
  43. S. Azmi, Z. Wang, P.A. Philip, R.M. Mohammad and F.H. Sarkar, Emerging Bcl-2 Inhibitors for the Treatment of Cancer, Expert Opin. Emerg. Drugs, 16, 59 (2011); https://doi.org/10.1517/14728214.2010.515210
  44. A.W. Bauer, W.M. Kirby, J.C. Sherris and M. Turck, Antibiotic Susceptibility Testing by a Standardized Single Disk Method, Am. J. Clin. Pathol., 45, 149 (1966).
  45. S.L. Dhonnar, R.A. More, V.A. Adole, B.S. Jagdale, N.V. Sadgir and S.S. Chobe, Synthesis, Spectral Analysis, Antibacterial, Antifungal, Antioxidant and Hemolytic Activity Studies of Some New 2,5-Disubstituted-1,3,4-oxadiazoles, J. Mol. Struct., 1253, 132216 (2022); https://doi.org/10.1016/j.molstruc.2021.132216
  46. G.M. Morris, R. Huey, W. Lindstrom, M.F. Sanner, R.K. Belew, D.S. Goodsell and A.J. Olson, AutoDock4 and AutoDockTools4: Automated Docking with Selective Receptor Flexibility, J. Comput. Chem., 30, 2785 (2009); https://doi.org/10.1002/jcc.21256
  47. N. Chinthakunta, S. Cheemanapalli, S. Chinthakunta, C. Anuradha and S.K. Chitta, A New Insight into Identification of in silico Analysis of Natural Compounds Targeting GPR120, Netw. Model. Anal. Health Inform. Bioinform., 7, 8 (2018); https://doi.org/10.1007/s13721-018-0166-0
  48. M.J. Ahsan, 1,3,4-Oxadiazole Containing Compounds as Therapeutic Targets for Cancer Therapy, Mini Rev. Med. Chem., 22, 164 (2021); https://doi.org/10.2174/1389557521666210226145837