Synthesis and Biological Evaluation of Imidazole-2-thione Fused Furazan as a New Biheterocyclic Scaffold

Gülşah Kurt; Fatih Sevgi

doi:10.29130/dubited.880667

TR EN

Yeni İki Hetero halkalı Bir Yapı Olarak İmidazol-2-tiyon ile Kaynaşmış Furazan Sentezi ve Biyolojik Değerlendirmesi

Abstract

İmidazole-2-tiyon grubunun furazan halkasıyla birleşmesinden oluşan iki heterohalkalı yeni bir bileşik sentez lenmiş ve biyolojik aktivitesi araştırılmıştır. Vic-dioksimlerinsilikajel destekli mikrodalga dehidrasyonunu içeren yeni bir stratejiyle, azot bakımından zengin heterohalkalar olan imidazol-2-tiyon ve 1,2,5-oksadiazol (furazan) uygun bir şekilde kaynaştırılmıştır. Hedeflenen furazan bileşiği olan “N,N’-difenil-4H-imidazo[4,5-c]furazan-5(6H)-tiyon" [II] (DFTFrz), kabul edilebilir bir verimle “(4E,5Z)-4,5-bis(hidroksimino)-N,N’-difenil imidazoli din-2-tiyon” [I] (DFTD) bileşiğinden sentezlendi ve LC-MS/MS, FT-IR ve NMR spektroskopisi metotlarıyla karakterize edildi. Elde edilen tiyoürefurazan ve çıkış maddesi dioksimin biyolojik değerlendirmesi, broth mikro dilüsyon ve disk diffüzyon yöntemlerini içeren antibakteriyel etki çalışmalarıyla araştırıldı. Tiyoüre furazanın test edilen patojenik bakteriler üzerinde öncülü olan dioksime göre daha etkili olduğu bulunmuştur. Bileşikler gram negatif bakteriler üzerinde herhangi bir etki göstermezken gram pozitif bakteriler özellikle de stafilakok türleri üzerinde orta derecede etki göstermiştir.

Keywords

Tiyoüre, Furazan, Imidazol-2-tiyon, İkili heterohalka, Antibakteriyel

Synthesis and Biological Evaluation of Imidazole-2-thione Fused Furazan as a New Biheterocyclic Scaffold

Abstract

A new imidazole-2-thione fused furazan biheterocyclic group was synthesized and its biological activity was investigated. Nitrogen rich heterocycles, imidazole-2-thione and 1,2,5-oxadiazole (furazan) have been conveni ently fused. To accomplish this, we have improved a new strategy that silica gel supported solvent free micro wave dehydration of vicinal dioximes. The target furazan "N,N’-diphenyl-4H-imidazo[4,5-c]furazan-5(6H) –thio ne" [II] (DFTFrz) was obtained from (4E,5Z)-4,5-bis(hydroxyimino)-N,N’-diphenylimidazolidine-2-thione [I] (DFTD) with acceptable yield and characterized by LC-MS/MS, FT-IR and NMR spectroscopy. The biological evaluation of the obtained thiourea furazan and its precursor dioxime were investigated by antibacterial effect studies using broth microdilution and disc diffusion methods. It was observed that thioure furazan was more effective on the tested pathogenic bacteria than its precursor dioxime. The compounds did not show any effect on gram negative bacteria, while they exhibited a moderate effect on gram positive bacteria, especially Staphylococcus spp.

Keywords

Thiourea, Furazan, Imidazole-2-thione, Biheterocyclic, Antibacterial

References

[1]R.A.Olofson, and J.S.Michelman, “Furazan,” 1, 2. The Journal of Organic Chemistry, vol.30, no.6, pp.1854-1859, 1965.
[2]L.F.Leonid and N.M.Nina, “Advances in the synthesis of non-annelated polynuclear hetero cyclic systems comprising the 1,2,5-oxadiazole ring,”Russian Chemical Reviews, vol. 85, no.10, pp. 1097-1145, 2016
[3]R.W.Beal and T.B.Brill, “Thermal Decomposition of Energetic Materials 77. Behavior of N-N Bridged Bifurazan Compounds on Slow and Fast Heating,”Propellants Explosives Pyrotechnics, vol, 25, no. 5, pp. 241-246, 2000.
[4]D. Fischer, T.M.Klapötke, M.Reymann, J.Stierstorfer, and M. B. R. Völkl, “Energetic alliance of tetrazole-1-oxides and 1,2,5-oxadiazoles,”New Journal of Chemistry, vol. 39, no.3, pp. 1619-1627, 2015.
[5]G.C.Tron, F.Pagliai, E.Del Grosso, A.A.Genazzani, and G.Sorba, “Synthesis and cytotoxic evaluation of combretafurazans, ”Journal of medicinal chemistry, vol. 48, no. 9, pp.3260-3268, 2005.
[6]G.Ohta, T.Takegoshi, K.Ueno, and M.Shimizu, “Investigations on Steroids. IV. Syntheses of Androstano [2, 3-c]-furazans and Related Compounds,”Chemical & Pharmaceutical Bulletin, vol. 13, no.12, pp.1445-1459, 1965.
[7]C.Velázquez, P.P.Rao, R.McDonald, and E.E.Knaus, “Synthesis and biological evaluation of 3,4- diphenyl-1, 2, 5-oxadiazole-2-oxides and 3, 4-diphenyl-1, 2, 5-oxadiazoles as potential hybrid COX-2 inhibitor/nitric oxide donor agents,”Bioorganic & medicinal chemistry, vol. 13, no.8, pp. 2749-2757, 2005.
[8]R.Calvino, A.Serafino, B.Ferrarotti, A.Gasco, and A.Sanfilippo, “Syntheses, Structures and Antimicrobial Properties of Some Halogenofuroxans and Related Furazans,”Archivder Pharmazie, vol. 317, no. 8, pp.695-701, 1984
[9]M.C.Das, S.Paul, P.Gupta, P.Tribedi, S.Sarkar, D.Manna, et al., “3-Amino-4-aminoximido furazan derivatives: small molecules possessing antimicrobial and antibiofilm activity against Staphyl ococcus aureus and Pseudomonas aeruginosa,”Journal of Applied Microbiology, vol.120, no. 4, pp. 842-859, 2016
[10]W.S.Li, S.V.More, C.H.Wang, Y.C.Jen, C.F.Yao, T.F. Wang, et al., “Synthesis and structure–activity relationships of novel furazan-3,4-diamide analogs as potent anti-cancer agents,” Bioorganic & Medicinal Chemistry Letters, vol.20, no. 3, pp.1148-1152, 2010.

[11]A.Gelain, M.Mori, F.Meneghetti, F.Porta, L.Basile, G.Marverti, et al., “Exploring the Biologi cal Activity of a Library of 1,2,5-Oxadiazole Derivatives Endowed with Antiproliferative Activity,” Anticancer Research, vol. 39, no.1, pp. 135-144, 2019.
[12]A.B.Sheremetev, D.E.Dmitriev, N.K.Lagutina, M.M.Raihstat, A.S.Kiselyov, M.N. Semenova, et al., “ New functionalized aminofurazans as potential antimitotic agentsin the sea urchin embryo assay,” Mendeleev Communications, vol. 20, no. 3, pp. 132-134, 2010.
[13]D.C.Schroeder, “Thioureas,” Chemical Reviews, vol.55, no. 1, pp. 181-228, 1955.
[14]A.Saeed, U.Flörke, and M.F.Erben, “A review on the chemistry, coordination, structure and biological properties of 1-(acyl/aroyl)-3-(substituted) thioureas,” Journal of Sulfur Chemistry, vol. 35,no. 3, pp. 318-355, 2014.
[15]I.L.Goncalves, G.O.de Azambuja, D.F.Kawano, and V.L.Eifler-Lima, “Thioureas as building blocks for the generation of heterocycles and compounds with pharmacological activity: an overview,”Mini-Reviews in Organic Chemistry, vol.15, no.1, pp.28-35, 2018.
[16]B.V.Trzhtsinskaya, and N.D.Abramova, “Imidazole-2-Thiones: Synthesis, Structure, Proper ties. Sulfur Reports,” vol.10, no.4, pp.389-421, 1991.
[17]A.Beheshti, E.Sadat Mousavifard, M.Kubicki, A.Grześkiewicz, and S.Elham Rezatofighi, “Tuning the structure of mercury (II) complexes as antibacterial agents by varying the halogen atoms (Cl and Br) and extending the spacer length of the imidazole-2-thione ligands,” Inorganica Chimica Acta, vol.514, no. 120010, 2021.
[18]D.Manna, G.Roy, and G.Mugesh, “Antithyroid Drugs and Their Analogues: Synthesis, Struc ture, and Mechanism of Action,” Accounts of Chemical Research, vol. 46, no.11, pp. 2706-2715, 2013.
[19]H.B.Burch, and D.S.Cooper, “Antithyroid drug therapy: 70 years later,” European journal of endocrinology, vol.179, no.5, pp. R261-R274, 2018.
[20]J. Xu , and J.C.Yadan, “Synthesis of L-(+)-Ergothioneine,” The Journal of Organic Chemis try, vol. 606296, pp. 6301, 1995.
[21] Q.Xu, C.H.Heo, G.Kim, H.W. Lee, H.M. Kim, and J.Yoon, “Development of imidazoline-2 Thiones Based Two-Photon Fluorescence Probes for Imaging Hypochlorite Generation in a Co-Cul ture System,” Angewandte Chemie International Edition, vol. 54, pp. 4890-4894, 2015
[22] Q.Xu,C.H.Heo, J.A.Kim, H.S.Lee, Y.Hu, D.Kim, K.M.K.Swamy, G.Kim, S.J.Nam, H.M.Kim and J. Yoon, “A Selective Imidazoline-2-thione-Bearing Two-Photon Fluorescent Probe for Hypochlo rous Acid in Mitochondria,” Analytical Chemistry, vol. 88, pp. 6615-6620, 2016.
[23]A.B.Sheremetev, “Chemistry of furazans fused to five-membered rings,” Journal of Hetero cyclic Chemistry, vol. 32, no. 2, pp. 371-385, 1995.
[24]B.S.Aleksei,“The chemistry of furazans fused to six- and seven-membered heterocycles with one heteroatom,” Russian Chemical Reviews, vol. 68, no.2, pp. 137-148, 1999.
[25]B.S.Aleksei, and L.Y.Igor, “Advances in the chemistry of furazano[3,4 -b]pyrazines and their analogues,” Russian Chemical Reviews, vol.72, no.1, pp.87-100, 2003.
[26]H.Gao, Q.Zhang, and J.N.M. Shreeve, “Fused heterocycle-based energetic materials,” Journal of Materials Chemistry A, vol.8, no.8, pp. 4193-4216, 2020.
[27]P.L, Vander Peet, T.U.Connell, C.Gunawan, J.M.White, P.S.Donnelly, and S.J.Williams, “A click chemistry approach to 5,5'-disubstituted-3,3'-bisisoxazoles from dichloroglyoxime and alkynes: luminescent organometallic iridium and rhenium bisisoxazole complexes,” J.Org Chem, vol.78, no.14, pp.7298-7304. 2013
[28]C.Grundmann, V.Mini, J.M. Dean, and H.D. Frommeld, “Über Nitriloxyde, IV. Dicyan-di-N-oxyd,”Justus Liebigs Annalen der Chemie, vol. 687, no.1, pp. 191-214, 1965.
[29]S.Serin, and Ö.Bekaroǧlu, “Synthesis and complex formation of stereoisomers of 1,3-Diphenyl-2-thioxo-4,5-bis(hydroxyimino)-Imidazoline,” Zeitschrift für anorganische und allgemeine Chemie, vol. 496, no.1, pp. 197-204, 1983.
[30]A.W.Bauer, W.M.M.Kirby, J.C.Sherris, and M.Turck, “Antibiotic Susceptibility Testing by a Standardized Single Disk Method,” American Journal of Clinical Pathology, vol. 45, no. 4, pp. 493-496, 1966.
[31]A.N. Kursunlu, E.Guler, F.Sevgi, and B.Ozkalp, “Synthesis, spectroscopic characterization and antimicrobialstudies of Co(II), Ni(II), Cu(II) and Zn(II) complexes with Schiff bases derived from 5-bromo-salicylaldehyde,”Journal of Molecular Structure, vol. 1048, pp. 476-481, 2013.
[32]B.Mercimek, M.A.Ozler, G.Irez, and Ö.Bekaroĝlu, “Synthesis of a Novel Heterocyclic Dioxi me and Its Mononuclear Complexes with Ni(II), Co(II), Cn(II), Zn(II), Cd(II) and Hg(II),” Synthesis and Reactivity in Inorganic and Metal-Organic Chemistry, vol. 29, no. 3, pp. 513-524, 1999.
[33]A.B.Sheremetev, Y.L.Shamshina, and D.E.Dmitriev, “Synthesis of 3-alkyl-4-amino furazans. Russian Chemical Bulletin,” vol. 54, no.4, pp. 1032-1037, 2005.
[34]A.I.Stepanov, D.V.Dashko, and A.A.Astrat’ev,“1,2-Di(4-R-furazan-3-yl)glyoximes: Synthesis by the Reduction of 3,4-Bis(4-R-furazan-3-yl)furoxans and Study of the Reactivity of these Compounds,” Chemistry of Heterocyclic Compounds, vol. 49, no.5, pp. 776-790, 2013
[35]M.Yadav, S.Shirude, D.Puntambekar, P.Patel, H.Prajapati, A.Parmar, et al., “Studies in 3, 4-diaryl-1,2,5-oxadiazoles and their N-oxides: Search for better COX-2 inhibitors,” Acta pharmaceutica, vol. 57, no.1, pp. 13-30, 2007.
[36]Y.Kamitori, “A convenient and facile synthesis of 3-trifluoromethyl-1,2,5-oxadiazoles with the use of silica gel as an effective catalyst,”Heterocycles, vol. 51, no.3, pp. 627-630, 1999.
[37] S.R.Martínez, D.M.Rocca, V.Aiassa, and M.C.Becerra, “Linezolid as an eradication agent against assembled methicillin-resistant Staphylococcus aureus biofilms,” RSC Advances, vol. 6, no.103, pp. 101023-101028, 2016.
[38]M.Boce, M.Tasse, S.Mallet-Ladeira, F.Pillet, C.Da Silva, P.Vicendo, et al., “Effect of trans (NO,OH)-[RuFT(Cl)(OH)NO](PF6) ruthenium nitrosyl complex on methicillin-resistant Staphyl ococcus epidermidis,” Scientific Reports, vol.9, no.1, pp. 15162, 2019.
[39]H.Nikaido,“The role of outer membrane and efflux pumps in the resistance of gram-negative bacteria. Can we improve drug access,” Drug Resistance Updates, vol.1, no. 2, pp. 93-98, 1998.
[40]M.F.Richter, B.S.Drown, A.P.Riley, A.Garcia, T.Shirai, R.L.Svec, et al.,“Predictive compo und accumulation rules yield a broad-spectrum antibiotic,” Nature, vol. 545, no.7654, pp. 299-304, 2017.

Details

Primary Language

English

Subjects

Engineering

Journal Section

Research Article

Authors

Gülşah Kurt ^*
0000-0001-5943-9307
Türkiye

Fatih Sevgi
0000-0002-5049-2053
Türkiye

Publication Date

January 31, 2022

Submission Date

February 15, 2021

Acceptance Date

June 18, 2021

Published in Issue

Year 2022 Volume: 10 Number: 1

DOI

https://doi.org/10.29130/dubited.880667

IZ

https://izlik.org/JA29XE53ZL

APA

Kurt, G., & Sevgi, F. (2022). Synthesis and Biological Evaluation of Imidazole-2-thione Fused Furazan as a New Biheterocyclic Scaffold. Duzce University Journal of Science and Technology, 10(1), 14-26. https://doi.org/10.29130/dubited.880667

AMA

1.Kurt G, Sevgi F. Synthesis and Biological Evaluation of Imidazole-2-thione Fused Furazan as a New Biheterocyclic Scaffold. DUBİTED. 2022;10(1):14-26. doi:10.29130/dubited.880667

Chicago

Kurt, Gülşah, and Fatih Sevgi. 2022. “Synthesis and Biological Evaluation of Imidazole-2-Thione Fused Furazan As a New Biheterocyclic Scaffold”. Duzce University Journal of Science and Technology 10 (1): 14-26. https://doi.org/10.29130/dubited.880667.

EndNote

Kurt G, Sevgi F (January 1, 2022) Synthesis and Biological Evaluation of Imidazole-2-thione Fused Furazan as a New Biheterocyclic Scaffold. Duzce University Journal of Science and Technology 10 1 14–26.

IEEE

[1]G. Kurt and F. Sevgi, “Synthesis and Biological Evaluation of Imidazole-2-thione Fused Furazan as a New Biheterocyclic Scaffold”, DUBİTED, vol. 10, no. 1, pp. 14–26, Jan. 2022, doi: 10.29130/dubited.880667.

ISNAD

Kurt, Gülşah - Sevgi, Fatih. “Synthesis and Biological Evaluation of Imidazole-2-Thione Fused Furazan As a New Biheterocyclic Scaffold”. Duzce University Journal of Science and Technology 10/1 (January 1, 2022): 14-26. https://doi.org/10.29130/dubited.880667.

JAMA

1.Kurt G, Sevgi F. Synthesis and Biological Evaluation of Imidazole-2-thione Fused Furazan as a New Biheterocyclic Scaffold. DUBİTED. 2022;10:14–26.

MLA

Kurt, Gülşah, and Fatih Sevgi. “Synthesis and Biological Evaluation of Imidazole-2-Thione Fused Furazan As a New Biheterocyclic Scaffold”. Duzce University Journal of Science and Technology, vol. 10, no. 1, Jan. 2022, pp. 14-26, doi:10.29130/dubited.880667.

Vancouver

1.Gülşah Kurt, Fatih Sevgi. Synthesis and Biological Evaluation of Imidazole-2-thione Fused Furazan as a New Biheterocyclic Scaffold. DUBİTED. 2022 Jan. 1;10(1):14-26. doi:10.29130/dubited.880667

Cited By

Recent advances in the synthesis of pharmacologically active 1,2,3-, 1,2,4-, and 1,2,5-oxadiazole-based lead compounds

Russian Chemical Reviews

https://doi.org/10.59761/RCR5185