SYNTHESIS AND EVALUATION OF BENZODIOXOLE APPENDED PYRAZOLINE DERIVATIVES AS NEW ANTIMICROBIAL AGENTS

Year 2015, Volume: 4 Issue: 1, 1 - 11, 12.01.2016

Mehlika Dilek Altıntop , Belgin Sever Ahmet Özdemir , Zafer Asım Kaplancıklı

Abstract

In the current work,new pyrazoline derivatives were synthesized via the reaction of 1-(chloroacetyl)-3-(2-thienyl)-5-(3,4-methylenedioxyphenyl)-2-pyrazoline with sodium salts of N,N-disubstituted dithiocarbamic acids. The compounds were investigated for their inhibitory effects on pathogenic bacteria and yeasts using broth microdilution method. MTT assay was carried out to determine the cytotoxic effects of the compounds on NIH/3T3 mouse embryonic fibroblast cell line. Among the tested compounds, 1-[[(4-(4-fluorophenyl)piperazin-1-yl)thiocarbamoylthio]acetyl]-3-(2-thienyl)-5-(3,4-methylendioxyphenyl)-2-pyrazoline (2) was found to be the most promising antimicrobial agent due to its notable inhibitory effects on Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli and Candida parapsilosis when compared with the reference agents. Compound 2 did not cause any toxicity against NIH/3T3 cell line. This outcome pointed out that the antimicrobial activity of compound 2 was selective.

Keywords

Benzodioxole; Dithiocarbamate; Pyrazoline; Antimicrobial activity; Cytotoxicity

BENZODİOKSOL HALKASI TAŞIYAN PİRAZOLİN TÜREVLERİNİN SENTEZİ VE YENİ ANTİMİKROBİYAL AJANLAR OLARAK DEĞERLENDİRİLMESİ

Abstract

Bu çalışmada, 1-(kloroasetil)-3-(2-tiyenil)-5-(3,4-metilendioksifenil)-2-pirazolinin N,N-disübstitüe ditiyokarbamik asitler ile reaksiyonuyla yeni pirazolin türevleri sentezlendi. Bileşikler, broth mikrodilüsyon yöntemi kullanılarak patojenik bakterilere ve mayalara karşı inhibitör etkileri için araştırıldı. Bileşiklerin NIH/3T3 fare embriyonik fibroblast hücre dizisine karşı sitotoksik etkilerini saptamak için MTT deneyi gerçekleştirildi. Referans maddeler ile kıyaslandığında test edilen bileşikler arasında, 1-[[(4-(4-florofenil)piperazin-1-il)tiyokarbamoiltiyo]asetil]-3-(2-tiyenil)-5(3,4-metilendioksifenil)-2-pirazolin (2) Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli ve Candida parapsilosis mikroorganizmaları üzerindeki dikkate değer inhibitör etkilerine bağlı olarak en umut verici antimikrobiyal ajan olarak bulundu. Bileşik 2, NIH/3T3 hücre dizisine karşı herhangi bir toksisiteye neden olmadı. Bu sonuç, bileşik 2’nin antimikrobiyal etkisinin seçici olduğunu gösterdi

Keywords

Benzodioksol, Ditiyokarbamat, Pirazolin, Antimikrobiyal etki, Sitotoksisite

References

• Altıntop, M.D., Kaplancıklı, Z.A., TuranZitouni, G., Özdemir, A., İşcan, G., Akalın, G., Ulusoylar Yıldırım, Ş. (2011). Synthesis and Anticandidal Activity of New Triazolothiadiazine Derivatives. European Journal of Medicinal Chemistry, 46, 5562-5566.
• Altintop, M.D., Özdemir, A., Kaplancikli, Z.A., Turan-Zitouni, G., Temel, H.E., A. Çiftçi, G. (2013). Synthesis and Biological Evaluation of Some Pyrazoline Derivatives Bearing a Dithiocarbamate Moiety as New Cholinesterase Inhibitors. Archiv der Pharmazie – Chemistry in Life Sciences, 346, 189-199.
• Attia, M.I., Kansoh, A.L., El-Brollosy, N.R. (2014). Antimicrobial Pyrimidinones II: Synthesis and Antimicrobial Evaluation of Certain Novel 5,6-Disubstituted 2- (substituted amino)alkylthiopyrimidin- 4(3H)-ones. Monatshefte für Chemie, 145, 1825-1837.
• Holla, B.S., Mahalinga, M., Ashok, M. and Karegoudar, P. (2006). Convenient Synthesis of Some 4′-MethtylthioContaining Aryl and Arylfuryl Pyrazolines and Their Antimicrobial Activity Studies. Phosphorus, Sulfur, and Silicon and the Related Elements, 181, 1427-1436.
• Kathiravan, M.K., Salake, A.B., Chothe, A.S., Dudhe, P.B., Watode, R.P., Mukta, M.S. and Gadhwe, S. (2012). The Biology and Chemistry of Antifungal Agents: A Review. Bioorganic and Medicinal Chemistry, 20(19), 5678-5698.
• Kumar, S. (2013). A Review on Anticonvulsant Activity of 1,3-Benzodioxole Ring System Based Compounds. International Journal of Pharmaceutical Sciences and Research, 4(9), 3296-3303.
• Malik, M.A., Al-Thabaiti, S.A. and Malik, M.A. (2012). Synthesis, Structure Optimization and Antifungal Screening of Novel Tetrazole Ring Bearing Acyl-Hydrazones. International Journal of Molecular Sciences, 13, 10880-10898.
• Moellering, R.C. Jr. (2011). Discovering New Antimicrobial Agents. International Journal of Antimicrobial Agents, 37(1), 2- 9.
• Mosmann, T. (1983). Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays. Journal of Immunological Methods, 65, 55-63.
• Munawar, M.A., Azad, M., Athar, M. and Groundwater, P.W. (2008). Synthesis and Antimicrobial Activity of QuinolineBased 2-Pyrazolines. Chemical Papers, 62(3), 288-293.
• Özdemir, A., Altıntop, M.D., Kaplancıklı, Z.A., Turan-Zitouni, G., Akalın Çiftçi, G., Demirci, F. (2014). Synthesis and Biological Evaluation of A New Series of Pyrazolines as New Anticandidal Agents. Pharmaceutical Chemistry Journal, 48(9), 605-614.
• Pierce, C.G. and Lopez-Ribot, J.L. (2013). Candidiasis Drug Discovery and Development: New Approaches Targeting Virulence for Discovering and Identifying New Drugs. Expert Opinion on Drug Discovery, 8(9), 1117-1126.
• Rahman, M.A. and Siddiqui, A.A. (2010). Pyrazoline Derivatives: A Worthy Insight into the Recent Advances and Potential Pharmacological Activities. International Journal of Pharmaceutical Sciences and Drug Research, 2(3), 165-175.
• Ramiz, M.M., El-Sayed, W.A., El-Tantawy, A. and Abdel-Rahman, A.A. (2010). Antimicrobial Activity of New 4,6- Disubstituted Pyrimidine, Pyrazoline, and Pyran Derivatives. Archives of Pharmacal Research, 33(5), 647-654.
• Rodrigues, C.F., Silva, S. and Henriques, M. (2014). Candida glabrata: A Review of Its Features and Resistance. European Journal of Clinical Microbiology and Infectious Diseases, 33, 673-688.
• Samshuddin, S., Narayana, B., Sarojini, B.K., Khan, M.T.H., Yathirajan, H.S., Raj, C.G.D. and Raghavendra, R. (2012). Antimicrobial, Analgesic, DPPH Scavenging Activities and Molecular Docking Study of Some 1,3,5-Triaryl-2- pyrazolines. Medicinal Chemistry Research, 21(8), 2012-2022.
• Sivakumar, P.M., Ganesan, S., Veluchamy, P. and Doble, M. (2010). Novel Chalcones and 1,3,5-Triphenyl-2-pyrazoline Derivatives as Antibacterial Agents. Chemical Biology and Drug Design, 6(5), 407-411