title: Green synthesis and anti-inflammatory studies of a series of 1,1-bis(heteroaryl)alkane derivatives.
abstract: Molecular iodine has been used as an efficient catalyst for a double Friedel-Crafts reaction of various heteroarenes, i.e. 2-methylfuran, 2-ethylfuran, 2-methylthiophene, pyrrole, N-methylpyrrole and indole, using aldehydes as alkylating agents under "open-flask" conditions with toluene or water as the reaction media. In the presence of 10 mol% iodine in toluene at room temperature, both aliphatic and aromatic aldehydes reacted smoothly to give the corresponding bis(heteroaryl)alkanes in good to excellent yields. Interestingly, with water as the solvent, the bis(heteroaryl)alkane adducts were obtained in moderate to good yields. The use of mild reaction conditions, low catalyst loadings, and eco-friendly reagents in a single step synthesis are the advantages of the present procedure. In an effort to discover novel non-steroidal anti-inflammatory agents, the synthesized bis(heteroaryl)alkanes were evaluated for the anti-inflammatory activity in the lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage model. These compounds (50 μM) significantly inhibited NO production and did not exhibit significant cytotoxic effects on macrophage cells. Among them, bis[(5-methyl)2-furyl](4-nitrophenyl) methane exhibited the most potent inhibition of NO with IC50 value of 42.4 ± 1.9, which is similar to that of the positive control, aminoguanidine (43.3 ± 2.5 μM). Thus, the bis[(5-methyl)2-furyl](4-nitrophenyl) methane could be considered a lead compound for the development of novel anti-inflammatory agents.
authors.affiliation: Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Burapha University, Chonburi 20131, Thailand. Electronic address: jaray@buu.ac.th.
authors.forename: Jaray
authors.initials: J
authors.lastname: Jaratjaroonphong
authors.affiliation: Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Burapha University, Chonburi 20131, Thailand.
authors.forename: Surisa
authors.initials: S
authors.lastname: Tuengpanya
authors.affiliation: Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Burapha University, Chonburi 20131, Thailand.
authors.forename: Rungnapha
authors.initials: R
authors.lastname: Saeeng
authors.affiliation: Biological Science Program, Faculty of Science, Burapha University, Chonburi 20131, Thailand; Department of Biochemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Burapha University, Chonburi 20131, Thailand.
authors.forename: Sarinporn
authors.initials: S
authors.lastname: Udompong
authors.affiliation: Department of Biochemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Burapha University, Chonburi 20131, Thailand.
authors.forename: Klaokwan
authors.initials: K
authors.lastname: Srisook
mesh_terms: D000473:Alkanes / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D055772:Green Chemistry Technology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D013329:Structure-Activity Relationship
chemical_list: D000473:Alkanes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D009569:Nitric Oxide
keywords: 1,1-Bis(heteroaryl)alkane; Anti-inflammatory agents; Iodine; Nitric oxide