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

Abstract

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

Crystal structure of 1-(5-acetyl-3,4-dimethyl-thieno[2,3-b]thiophen-2-yl)- ethanone, C12H12O2S2

“…Some thieno [2,3-b]thiophene derivatives also inhibit several important enzymes in cellular systems, such as a-glucosidase and b-glucuronidase inhibition, or exhibited DPPH radical scavenging antioxidant activity [9][10]. The title compound is composed of two planar thiophene rings (S1/C2-C5 and S1A/C2A-C5A) with maximum deviation of 0.005(1) Å for C2 atom from rmsplane.…”

S-NICS Investigation for Heterocyclic Anticancer Compounds

“…Many of heterocyclic compounds are known as anticancer drugs such as alkylating agents which have targeted cell DNA causing cell death. Heterocycles 1 structures are composed by atoms other than carbon, where the most times substituents are sulfur, oxygen 1 and nitrogen 1,2 .The model size of heterocycles ring, together with the substituent group of the core scaffold 2 , impact tightly on the chemical and physical properties 3 while among the clinical applications, heterocyclic compound has an active role as anti-bacterial 4,5 , anti-viral 6 , anti-fungal 7 , antiinflammatory 8 and anti-tumor drugs [9][10][11] .…”

“…Heterocyclic structures played an important behavior in the metabolism 11 of all cells; maximum number of them is 6 (or sometimes 5) membered hetero-cycles including one to three heteroatoms 11 . Recently, imidazole fragment has been attracting much concentration because of its role as attractive scaffold for biochemical active heterocyclic 11 drugs…”

“…Structure activities relationship was reduced 9 from biological results and will be used in further design 11 of new active compounds. Currently, a number of drugs are used in the treatment 11 of the cancer, but most of them were produced controlled effect on the cancer cells.…”

“…Structure activities relationship was reduced 9 from biological results and will be used in further design 11 of new active compounds. Currently, a number of drugs are used in the treatment 11 of the cancer, but most of them were produced controlled effect on the cancer cells. The usual applications of heterocycles are as vast as it is diverse and is not extensively 9 encompassed in the scope 10 of that study.…”