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

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 Br(2)/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 (IC(50) = 56.26 ± 3.18 μM) showed a potent DPPH radical scavenging antioxidant activity and found to be more active than standard N-acetylcystein (IC(50) = 105.9 ± 1.1 μM). Compounds 8a (IC(50) = 13.2 ± 0.34 μM) and 8b (IC(50) = 14.1 ± 0.28 μM) found as potent inhibitor of α-glucusidase several fold more active than the standard acarbose (IC(50) = 841 ± 1.73 μM). Most promising results were obtained in β-glucuronidase enzyme inhibition assay. Compounds 5 (IC(50) = 0.13 ± 0.019 μM), 6 (IC(50) = 19.9 ± 0.285 μM), 8a (IC(50) = 1.2 ± 0.0785 μM) and 9 (IC(50) = 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 (IC(50) = 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.