Synthesis, reactions and biological activity of some new bis-heterocyclic ring compounds containing sulphur atom

Chemistry Central Journal

Yahia Nasser Mabkhot³  Assem Barakat¹  Abdullah Mohammed Al-Majid³  Saeed Alshahrani³  Sammer Yousuf²  M Iqbal Choudhary² 

[1] Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia 21321, Alexandria, Egypt

[2] H.E.J. Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi 75270, Pakistan

[3] Department of Chemistry, Faculty of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia

关键词: Cancer cell line;    Ctotoxicity;    DPPH radical scavenging activity;    α-glucosidase inhibition;    β-glucuronidase inhibition;    Bisheterocycles;    Thiazole;    Imidazole;    Oxazole;    Thienothiophene;   

Others  :  787881
DOI  :  10.1186/1752-153X-7-112

 received in 2013-04-02, accepted in 2013-06-28,  发布年份 2013

【 摘 要 】

Background

The derivatives of thieno[2,3-b]thiophene belong to a significant category of heterocyclic compounds, which have shown a wide spectrum of medical and industrial application.

Results

A new building block with two electrophilic center of thieno[2,3-b]thiophene derivatives 2 has been reported by one-pot reaction of diketone derivative 1 with Br₂/AcOH in excellent yield. A variety of heteroaromatics having bis(1H-imidazo[1,2a] benzimidazole), bis(1H-imidazo[1,2-b][1,2,4]triazole)-3-methyl-4-phenylthieno[2,3-b]thiophene derivatives, dioxazolo-, dithiazolo-, and 1H-imidazolo-3-methyl-4-phenylthieno[2,3-b]thiophene derivatives as well pyrrolo, thiazolo -3-methyl-4-phenylthieno[2,3-b]thiophene derivatives have been designed, synthesized, characterized, and evaluated for their biological activity. Compounds 3–9 showed good bioassay result. These new derivatives were evaluated for anti-cancer activity against PC-3 cell lines, in vitro antioxidant potential and β-glucuronidase and α-glucosidase inhibitory activities. Compound 3 (IC₅₀ = 56.26 ± 3.18 μM) showed a potent DPPH radical scavenging antioxidant activity and found to be more active than standard N-acetylcystein (IC₅₀ = 105.9 ± 1.1 μM). Compounds 8a (IC₅₀ = 13.2 ± 0.34 μM) and 8b (IC₅₀ = 14.1 ± 0.28 μM) found as potent inhibitor of α-glucusidase several fold more active than the standard acarbose (IC₅₀ = 841 ± 1.73 μM). Most promising results were obtained in β-glucuronidase enzyme inhibition assay. Compounds 5 (IC₅₀ = 0.13 ± 0.019 μM), 6 (IC₅₀ = 19.9 ± 0.285 μM), 8a (IC₅₀ = 1.2 ± 0.0785 μM) and 9 (IC₅₀ = 0.003 ± 0.09 μM) showed a potent inhibition of β-glucuronidase. Compound 9 was found to be several hundred fold more active than standard D-Saccharic acid 1,4-lactone (IC₅₀ = 45.75 ± 2.16 μM).

Conclusions

Synthesis, characterization, and in vitro biological activity of a series of thieno[2,3-b]thiophene have been investigated.

【 授权许可】

   
2013 Mabkhot et al.; licensee Chemistry Central Ltd.

【 图 表 】

Scheme 1

Scheme 2

Scheme 3

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