In Vitro Antimicrobial Activities of 6-Substituted-3(2H)- pyridazinone-2-acetyl-2- (substituted/nonsubstitutedbenzal/ acetophenone) Hydrazone Derivatives

Open access


Aim: In vitro antibacterial activity of 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(substituted/nonsubstitutedbenzal/ acetophenone) hydrazone derivatives were tested in common species causing hospital-acquired infections. Material and Method: Antimicrobial activities of the compounds were performed by determining minimum inhibitory concentration (MIC) value against four Gram-positive, five Gram-negative and four Candida species fungi. Modified serial microdilution method was carried out. Reference strains of American Type Culture Collection (ATCC) were used. Results: In general, eleven compounds exhibited considerable activity. Comparatively, compound 3 exhibited strong activity against Enterobacter hormaechei and 5, 11 were the most active against Acinetobacter baumannii at 31.25 μg/mL. Compounds 1,2,3,4,8 and 10 were found to be as active as positive control ampicillin trihidrate against Stenotrophomonas maltophilia. On the other hand, compounds 1,2,3,4,7,8,9,10 and 11 showed strong antifungal activitiy as much as fluconazole against Candida tropicalis. Compound 1 was mostly active against Candida albicans, Candida glabrata, Candida parapsilosis and Candida tropicalis. It was also revealed that the antifungal activity of compounds 1, 6, 7, 8 and 9 were higher than the others. Compound 1 and 8 exhibited the best activity against Candida glabrata and Candida parapsilosis respectively. Conclusions: All tested compounds showed better activity against Gram-negative bacteria and yeast than Gram-positive bacteria. These compounds may be considered as alternative antimicrobial agents in the treatment of multiple drug resistant Gram-negative, Gram-positive bacteria and fungal pathogens. Especially, we suggested that Compound 1 and 8 might be a promising candidate of new antifungal agents

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. Nolte O. Antimicrobial resistance in the 21st century: a multifaceted challenge. Protein Pept Lett 2014; 21:330-5. DOI: 10.2174/09298665113206660106

  • 2. Thabit Ak Crandon JL Nicolau DP. Antimicrobial resistance: impact on clinical and economic outcomes and the need for new antimicrobials. Expert Opin Pharmacother 2015;16(2):159-77. DOI: 10.1517/14656566.2015.993381

  • 3. MacCarthy MW Kontoyiannis DP Cornely OA Perfect JR Walsh TJ. Novel Agents and Drug Targets to Meet the Challenges of Resistant Fungi. J Infect Dis 2017;216:474-83. DOI: 10.1093/infdis/jix130

  • 4. Rai M Ingle AP Pandit R Paralikar P Gupta I Chaud MV Dos Santos CA. Broadenin the spectrum of small-molecule antibacterials by metallic nanoparticles to overcome microbial resistance. Int J Pharm 2017;532:139-148. DOI: 10.1016/j.ijpharm.2017.08.127

  • 5. Ibrahim HM Behbehani H Elnagdi MH. Approaches towards the synthesis of a novel class of 2-amino- 5-arylzonicotinate pyridazinone and pyrido[23-d] pyrimidine derivatives as potent antimicrobial agents. Chem Cent J 2013;7(1):123. DOI: 10.1186/1752-153X-7-123

  • 6. Singh J Sharma D Bansal R. Pyridazinone:an attractive lead for ant-inflamatory and analgesic drug discovery. Future Med Chem 2017;9(1):95-127. DOI: 10.4155/fmc-2016-0194

  • 7. Jaballah MY Serya RT Abouzid K. Pyridazinone Based Scaffods as Privileed Structures in anti-cancer Therapy. Drug Res (Stuttg) 2017;67(3):138-48. DOI: 10.1055/s-0042-119992

  • 8. Asif M. A mini review on biological activities pf pyridazinone derivatives as antiulcer antisecretory antihistamin and particularly against histamine H3R. Mini Rev Med Chem 2015;14(3):1093-103. DOI: 10.2174/1 389557514666141127143133

  • 9. Sukuroglu M Onkol T Onurdag FK Akalin G Sahin MF. Synthesis and in vitro biological activity of new 46-disubstituted 3(H)-pyridazinone-acetohydrazide derivatives. Z Naturforsch C 2012;67(5-6):257-65. DOI: 10.5560/ZNC.2012.67c0257

  • 10. Bansal R Sridhar T. Pyridazin-3(2H)-ones: the versatile pharmacophore of medicinal significance. Med Chem Res 2013;22:2539-52. DOI: 10.1007/s00044- 012-0261-1

  • 11. Purohit DM Shah VH. Novel method for synthesis and antimicrobial evaluation of 2-aroyl-6-hydroxy/chloro/ hydrazino/carboxymethoxy-3(2H)-pyridazinones. Heterocycl Commun 1997;3 (3):267-272. DOI: 10.1515/HC.1997.3.3.267

  • 12. Islam M Siddiqui AA Rajesh R. Synthesis antitubercular antifungal and antibacterial activities of 6-susbtituted phenyl-2-(3’-substituded phenyl pyridazin- 6’-yl)-2345-tetrahydropyridazin-3-one. Acta Pol Pharm 2008;65(3):353-62.

  • 13. Ozcelik AB Gokce M Orhan I Kaynak F Sahin MF. Synthesis and antimicrobial acetylcholinesterase and butyrycholinesterase inhibitory activities of novel ester and hydrazide derivatives of 3(H)-pyridazinone. Arnzeimittelforschung 2010;60(7):452-8.

  • 14. Sonmej M Berber L Akbas B. Synthesis antibacterial and antifungal activity of some new pyridazinone metal complexes. Eur J Med Chem 2005;41:101-5. DOI: 10.1016/j.ejmech.2005.10.003

  • 15. Akbas E Berber I. Antibacterial and antifungal activities of new pyrazolo [34-d]pyridazin derivatives Eur J Med Chem 2005;40:401-5. DOI: 10.1016/j.ejmech. 2004.12.001

  • 16. Utku S Gokce M Aslan G Bayram G Ulger M Emekdaş G et al. Synthesis and in vitro antimycobacterial activities of novel 6-substituted-3(2H)-pyridazinone- 2-acetyl-2-(substituted/nonsubstituted acetophenone) hydrazine. Turk J Chem 2011;35(2):331-9.

  • 17. Gokce M Utku S Kupeli E. Synthesis and analgesic and anti-inflammatory activities 6-substituted-3(2H)-pyridazinone- 2-acetyl-2-(p-substituted/nonsubstituted benzal) hydrazone derivatives. Eur J Med Chem 2009;44:3760-64. DOI: 10.1016/j.ejmech.2009.04.048

  • 18. Jorgensen JH Ferraro MJ. Antimicrobial suspectibility testing: general principles and comtemporary. Clin Infect Dis 1998;26:973-80. DOI: 10.1086/513938

  • 19. Woods GL Washington JA Antibacterial susceptibility tests: dilution and disk diffusion methods. In: Murray PR Baron EJ Pfaller MA Tenover FC Yolken RH eds. Manual of clinical microbiology. 6th ed. Washington DC: American Society for Microbiology; 1995:1327-41.

  • 20. Clinical Laboratory Standards Institute. Performance Standards For Antimicrobial Susceptibility Testing; Twenty-Second Informational Supplement. CLSI. M02-A11 and M07-A9 2012:40-61.

  • 21. [Last accested 1 August 2017].

  • 22. Lob SH Badal RE Hackel MA Sahm DF. Epidemiology and antimicrobial Suspectibility of Gram-Negative Pathogens Causing Intra-abdominal Infections in Pediatrics Patients in Europe-SMART 2011-2014. J Pediatric Infect Dis Soc 2017;6(1):72-79

  • 23. Akova M. Epidemiology of antimicrobial resistance in bloodstream infections. Virulence 2016;7(3):252-66. DOI: 10.1080/21505594.2016.1159366

  • 24. Karlowksy JA Hoban DJ Hackel MA Lob SH Sahm DF. Resistance among Gram-negative ESKAPE pathogens isolated from hospitalized patients with intra-abdominal and urinary tract infections in Latin American countries: SMART 2013-2015. Braz J Infect Dis 2017;21(3):343-8. DOI: 10.1016/j.bjid.2017.03.006

  • 25. Koksal F Yılmaz G Unal S Zarakolu P Korten V Mulazzimoglu L et al. Epidemiology and susceptibility of pathogens from SMART 2011-12 Turkey: evaluation of hospital-acquired versus community-acquired urinary tract infections and ICU- versus non-ICU-associated intra-abdominal infections. J Antimicrob Chemother 2017;72: 1364-72. DOI: 10.1093/jac/dkw574

  • 26. Bernabe KJ Langendorf C Ford N Ronat JB Murphy RA. Antibiotic resistance in West Africa: a systematic review and meta-analysis. International Journal of Antimicrobial Agent 2017;17: 30274-1.

  • 27. Kelly AM Mathema B Larson EL. Carbapenem-resistant Enterobacteriaceae in the community: a scoping review. Int J Antimicrob Agents 2017;50:127-134. DOI: 10.1016/j.ijantimicag.2017.03.012

  • 28. Srinivasan A Lopez-Ribot JL Ramasubramanian AK. Overcoming antifungal resistance. Drug Discov Today Technol 2014:65-71. DOI: 10.1016/j.ddtec.2014.02.005

  • 29. Maubon D Garnaud C Calandra T Sanglard D Cornet M. Resistance of Candida spp. to antifungal drugs in the ICU: where are we now?. Intensive Care Med 2014;40:1241-55. DOI: 10.1007/s00134-014-3404-7

  • 30. Ben-Ami R Olshtain-Pops K Krieger M et al. Antibiotic exposure as a risk factor for fluconazole-resistant Candida bloodstream infection. Antimicrob Agents Chemother 2012; 56: 2518-2523. DOI: 10.1128/AAC.05947-11

  • 31. Arendrup MC. Update on antifungal resistance in Aspergillus and Candida Clin Microbiol Infect 2014; 20 (Suppl. 6): 42-48.

Journal information
Impact Factor

IMPACT FACTOR 2018: 0.800
5-year IMPACT FACTOR: 0.655

CiteScore 2017: 0.31

SCImago Journal Rank (SJR) 2018: 0.194
Source Normalized Impact per Paper (SNIP) 2018: 0.306

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 350 220 6
PDF Downloads 200 138 4