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

ABSTRACT:

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 ?-glucuronidase and ?-glucosidase inhibitory activities. Compound 3 (IC50?=?56.26?±?3.18??M) showed a potent DPPH radical scavenging antioxidant activity and found to be more active than standard N-acetylcystein (IC50?=?105.9?±?1.1??M). Compounds 8a (IC50?=?13.2?±?0.34??M) and 8b (IC50?=?14.1?±?0.28??M) found as potent inhibitor of ?-glucusidase several fold more active than the standard acarbose (IC50?=?841?±?1.73??M). Most promising results were obtained in ?-glucuronidase enzyme inhibition assay. Compounds 5 (IC50?=?0.13?±?0.019??M), 6 (IC50?=?19.9?±?0.285??M), 8a (IC50?=?1.2?±?0.0785??M) and 9 (IC50?=?0.003?±?0.09??M) showed a potent inhibition of ?-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??M).

Conclusions

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

SUBMITTER: Mabkhot YN 

PROVIDER: S-EPMC3728144 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature