SYNTHESIS and ANTIMICROBIAL ACTIVITY of SOME NOVEL QUINOXALINE HYDRAZONES

Year 2015, Volume: 4 Issue: 1, 31 - 39, 12.01.2016

Esra Başyiğit Ulviye Acar Çevik , Yusuf Özkay , Hülya Karaca Gençer , Ümit Uçucu

Abstract

A new class of 10 novel quinoxaline hydrazones was synthesized to examine their antimicrobial activity. The structural of the compounds was confirmed by IR, ¹H-NMR, and MS spectral data and elemental analyses. Antimicrobial activity of the compounds was evaluated against 3 fungal and 7 bacterial strains by Micro-broth dilution assay. All of the synthesized compounds indicated showed significant antibacterial activity against Pseudomonas aeruginosa. Furthermore, antibacterial activity of the 2,4-difluoro substituted compound 4b displayed two fold better activity than chloramphenicol against this bacterial strain.  

Keywords

Quinoxaline, Hydrazone, Antimicrobial activity, Micro-broth dilution, Pseudomonas aeruginosa

BAZI YENİ KİNOKSALİN HİDRAZONLARIN SENTEZİ ve ANTİMİKROBİYAL AKTİVİTELERİ

Abstract

10 yeni kinoksalin hidrazondan oluşan yeni bir grup aktimikrobiyal aktivitesi incelenmek üzere sentezlenmiştir. Bileşiklerin yapıları IR, 1H-NMR, MS spektral ve elemental analiz ile aydınlatılmıştır. Bileşiklerin antimikrobiyal aktiviteleri Mikro-broth dilüsyon yöntemi ile 3 fungus ve 7 bakteri türüne karşı değerlendirilmiştir. Sentezlenen bütün bileşikler Pseudomonas aeruginosa’ ya karşı önemli antibakteriyal aktivite göstermiştir. Ayrıca, 2,4-difloro yapısı içeren 4b bileşiği Pseudomonas aeruginosa’ ya karşı kloramfenikolden 2 kat daha iyi antibakteriyal aktivite göstermiştir

Keywords

Kinoksalin, Hidrazon, Antimikrobiyal aktivite, Mikro-broth dilüsyon

References

• Akhand, S.S., Pettit, R.S., Gardner, T.E., Anderson, G.G. (2014). New treatments in development for Pseudomonas aeruginosa Infections in the Lungs of Individuals with Cystic Fibrosis. Orphan Drugs Research and Reviews 4.
• Backes, G.L., Neumann, D.M., Jursic, B.S. (2014). Synthesis and Antifungal Activity of Substituted Salicylaldehyde Hydrazones, Hydrazides and Sulfohydrazides. Bioorganic & Medicinal Chemistry 22(17), 4629–4636.
• Becker, I. (2008). Preparation of derivatives of 1-(2-pyrimidinyl) Piperazine as Potential Antianxiety, Antidepressant, and Antipsychotic Agents. Journal of Heterocyclic Chemistry 45: 1005-1022.
• Carta, A., Paglietti, G., Nikookar, M.E.R., Sanna, P., Sechi, L., Zanetti, S. (2002). Novel Substituted Quinoxaline 1,4-dioxides with in vitro Antimycobacterial and Anticandidal Activity. European Journal of Medicinal Chemistry 37(5), 355–366.
• Chen, C.Y., Lin, T.P., Chen, C.K., Lin, S.C., Tseng, M.C., Wen, Y.S., Sun, S.S. (2008). New Chromogenic and Fluorescent Probes for Anion Detection:  Formation of a [2+2] Supramolecular Complex on Addition of Fluoride with Positive Homotropic Cooperativity. Journal of Organic Chemistry 73(3), 900-911.
• CLSI. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically Approved Standard, CLSI Document M7-A7, seventhed. (2006). ISBN1-56238-587-9.
• El-Faham, A., El-Massry, A.M., Amer, A., Gohar, Y.M. (2002). A Versatile Synthetic Route to Chiral Quinoxaline Derivatives from Aminoacids Precursors. Letters Peptide Science 9(1), 49–54.
• El-Sabbagh, OI., El-Sadek, M.E., Lashine, S.M., Yassin, S.H., El-Nabtity, S.M. (2009). Synthesis of new 2(1H)-Quinoxalinone Derivativesfor Antimicrobial and Antiinflammatory Evaluation. Medicinal Chemistry Research 18(9), 782–797.
• Ishikawa, H., Sugiyama, T., Kurita, K., Yokoyama, A. (2012). Synthesis and Antimicrobial Activity of 2,3Bis(bromomethyl)quinoxaline Derivatives. Bioorganic Chemistry 41:1–5.
• Ishikawa, H., Sugiyama, T., Yokoyama, A. (2013). Synthesis of 2,3bis(halomethyl)quinoxaline Derivatives and Evaluation of Their Antibacterial and Antifungal Activities. Chemical and Pharmaceutical Bulletin 61(4), 438–444.
• Kamal, A., Babu, K.S., Faazil, S., Ali Hussaini, S.M., Shaik, A.B. (2014). L-Proline Mediated Synthesis of Quinoxalines; Evaluation of Cytotoxic and Antimicrobial Activity. Royal Society of Chemistry 4(86), 46369–46377.
• Khaksar, S., Tajbakhsh, M., Gholami, M., Rostamnezhad, F.A. (2014). Highly efficient Procedure for the Synthesis of Quinoxaline Derivatives using Polyvinylpolypyrrolidone Supported Triflic Acid Catalyst. Chinese Chemical Letters 25(9), 1287–1290.
• Khan, J., Wahab, A., Qayyum, A., Jamshed, S. (2014). Drug Resistance Pattern of Pseudomonas aeruginosa isolates at PIMS Hospital. Journal of Chemical and Pharmaceutical Research 6(11), 715-719.
• Kotharkar, S.A., Shinde, D.B. (2006). Synthesis of antimicrobial 2,9,10-trisubstituted-6-oxo7,12-dihydro-chromeno[3,4-b]quinoxalines. Bioorganic & Medicinal Chemistry Letters 16(24), 6181–6184.
• Nagaraj, K., Ambika, S., Arunachalam, S. (2015). Synthesis, CMC Determination, and Intercalativebinding Interaction with Nucleic Acid of Asurfactant–copper(II) complex with Modified Phenanthroline Ligand (dpq). Journal of Biomolecular Structure and Dynamics 33(2), 274-288.
• Narasimhan, B., Kumar, P., Sharma, D. (2010). Biological Activities of Hydrazide Derivatives in the New Millennium. Acta Pharmaceutica Sciencia 52:169-180.
• Poole, K. (2014). Stress Responses as Determinants of Antimicrobial Resistance in Pseudomonas aeruginosa: Multidrug Efflux and More. Canadian Journal of Microbiology 60:783-791.
• Ramalingam, P., Ganapaty, S., Rao, C.B. (2010). In vitro Antitubercular and Antimicrobial Activities of 1-Substituted Quinoxaline-2,3(1H,4H)-diones. Bioorganic & Medicinal Chemistry Letters 20(1), 406– 408.
• Sıngh, D.C.P., Hashım, S.R., Sınghal R.G. (2011). Synthesis and Antimicrobial Activity of Some New Thioether Derivatives of Quinoxaline. E-Journal of Chemistry 8(2), 635-642.
• Soliman, A.M., Amer, A.A. (2012). Synthesis and Antimicrobial Activity of Some Novel Quinoxalines. Synthetic Communications 42(10), 1401–1410.
• Ulbrich, K., Subr, V. (2004). Polymeric Anticancer Drugs with pH-controlled Activation. Advanced Drug Delivery Reviews, 56(7), 1023-1050.
• Veerappa, K., Babu, Y., Siddanakatte, D. (2014). The Influence of Imipenem Resistant Metallo-Beta-Lactamase Positive and Negative Pseudomonas aeruginosa Nosocomial Infections on Mortality and Morbidity. Journal of Natural Science Biology & Medicine 5(2), 345-351.
• Vieira, M., Pinheiro, C., Fernandes, R., Noronha, J.P., Prudencio, C. (2014). Antimicrobial Activity of Quinoxaline 1,4Dioxide with 2- and 3-substituted Derivatives. Microbiol Research 169(4), 287– 293.
• Yan-Yan, H. (2010). An Efficient Synthesis of 3-(indol-3-yl)quinoxalin-2-ones with TfOHCatalyzed Friedel–Crafts Type Coupling Reaction in Air. Tetrahedron Letters 51(15), 2023-2028.
• Yurttaş, L., Özkay, Y., Karaca, H., Tunalı, Y., Kaplancıklı. Z.A. (2013). Synthesis and Antimicrobial Evaluation of Some 2,5Disubstituted Benzimidazole Derivatives. Letters in Drug Design & Discovery 10(6), 486-491.
• Wayne, P.A. (2008). CLSI document M27-A3, Clinical and Laboratory Standards Institute.
• Wu, J., Wang, J., Hu, D., He, M., Jin, L., Song, B. (2012). Synthesis and Antifungal Activity of Novel Pyrazolecarboxamide Derivatives Containing Hydrazone Moiety. Chemistry Central Journal 6:51.
• Zhang, M., Dai, Z.C., Qian, S.S., Liu, J.Y., Xiao, Y., Lu, A.M., Zhu, H.L., Wang, J.X., Ye, Y.H. (2014). Design, Synthesis, Antifungal, and Antioxidant Activities of (e‑6-((2Phenylhydrazono)methyl)quinoxaline Derivatives. Journal of Agricultural and Food Chemistry 62(40), 9637−9643.