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Synthesis of some 3,4-disubstituted-6,7-dihydro-imidazo[2,1-b][1,3]thiazole and 3,4-disubstituted-7,8-dihydro-6H-imidazo[2,1-b][1,3]thiazine derivatives and evaluation of their cytotoxicities against F2408 and 5RP7 cells

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Abstract

This article describes the synthesis of 3,4-disubstituted-6,7-dihydro-imidazo[2,1-b][1,3]thiazoles and 3,4-disubstituted-7,8-dihydro-6H-imidazo[2,1-b][1,3]thiazines, having substituted or nonsubstituted phenyl rings at the 5,6 and 2,3 positions, respectively, their cytotoxic effects through noncancer (F2408) and cancer (5RP7) cells, and their detailed 1H- and 13C-nuclear magnetic resonance (NMR) spectral characterization. The title compounds were obtained by the cyclization of 4,5-diaryl-imidazole-2-thione and dihaloalkane (i.e., 1,2-dihaloethane or 1,3-dihalopropane), in the presence of potassium carbonate (K2CO3) in N,N-dimethyl formamide (DMF). 4,5-Diaryl-imidazole-2-thione was prepared by condensation of α-hydroxyketones (acyloins), which were obtained by treating aldehydes with cyanide, with thioureas in AcOH. The structure of imidazo[2,1-b][1,3]thiazole and imidazo[2,1-b][1,3]thiazine derivatives was confirmed by infrared (IR), 1H-NMR, and 13C-NMR. The cytotoxicities of the synthesized compounds on both of noncancer (F2408) and cancer (5RP7) cells were measured by 3-(4,5-dimethyl-thiazollyl-2)-2,5-diphenyltetrazolium (MTT) assay. In the presence of only lower doses of compounds 9 and 11, bearing methyl or methoxy substituents on the phenyl ring of imidazo[2,1-b][1,3]thiazole scaffold, the cytotoxic effect was higher on 5RP7 cells than control cells after 24 h.

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Acknowledgements

This study was supported in part by the Anadolu University Scientific Research Projects Foundation, AÜBAP, Eskişehir-TÜRKİYE (Project no. 990321/2000). The authors would like to thank AÜBAP and are grateful to the facilities of Anadolu University Medicinal and Aromatic Plant and Drug Research Center (AÜBİBAM, TR). They would also like to thank Novruz Akhmedov, PhD (University of Florida, Department of Chemistry, Gainesville) for his valuable contributions on the NMR analysis and Mutlu D. Aytemir, PhD (Hacettepe University, Department of Pharmaceutical Chemistry, Ankara-Türkiye) for her SciFinder screening study.

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  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470, Eskişehir, Turkey

    Asiye Meriç

  2. Department of Biochemistry, Faculty of Pharmacy, Anadolu University, 26470, Eskişehir, Turkey

    Zerrin İncesu & İbrahim Hatipoğlu

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  1. Asiye Meriç
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  2. Zerrin İncesu
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Correspondence to Asiye Meriç.

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Meriç, A., İncesu, Z. & Hatipoğlu, İ. Synthesis of some 3,4-disubstituted-6,7-dihydro-imidazo[2,1-b][1,3]thiazole and 3,4-disubstituted-7,8-dihydro-6H-imidazo[2,1-b][1,3]thiazine derivatives and evaluation of their cytotoxicities against F2408 and 5RP7 cells. Med Chem Res 17, 30–41 (2008). https://doi.org/10.1007/s00044-008-9090-7

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