Synthesis of 1,4‐Anthracene‐9,10‐dione Derivatives and Their Regulation of Nitric Oxide, IL‐1β and TNF‐α in Activated RAW264.7 Cells

Abstract

Mitoxantrone is an anthracenedione antineoplastic and immunosuppressive agent approved for multiple sclerosis treatment. Novel mono- and disubstituted anthraquinone derivatives, analogues of mitoxantrone, were synthesized through the addition of lipophilic amino alcohols and evaluated for their effect on IL-1β, TNF-α and nitric oxide production by LPS/IFN-γ-stimulated RAW264.7 cells. The disubstituted 1,4-anthracene-9,10-dione 10 showed significant inhibition of nitric oxide, TNF-α and IL-1β production at the concentration of 5 μg/mL, with a much lower cytotoxicity than mitoxantrone. The monosubstituted 3, 4, 11, 12 and 13 also displayed a moderate to good inhibitory capacity on IL-1β production. However, the methylated compounds 11, 12 and 13 failed to inhibit the TNF-α production, and compound 13 was the only one to decrease the production of nitric oxide. None of these derivatives was toxic at the tested concentrations. Compounds 10 and 13 had better inhibitory capacity of the inflammatory mediators analyzed, with reliable viability of the cells.

Synthesis and Biological Evaluation of 5‐Nitropyrimidine‐2,4‐dione Analogues as Inhibitors of Nitric Oxide and iNOS Activity

“…Normally, NO is expressed by eNOS and nNOS at a low level; while activated proinflammatory cytokines or lipopolysaccharide (LPS), the iNOS produces a high level of NO to exert immune defense against pathogens at the inflammatory site . Aberrant iNOS‐mediated NO biosynthesis, located in macrophages, has been involved in a variety of pathological and physiological diseases including septic stroke, hypertension, cancer, ischemia, and rheumatoid arthritis . Therefore, pharmacological reduction of iNOS‐mediated NO production is regarded as one of the essential conditions to alleviate a variety of acute and chronic inflammatory diseases.…”

Recent advances in the syntheses of anthracene derivatives

“…ple, in 2008, Deiters and co-workers described an efficient twostep route to prepare substituted anthracenes and azaanthracenes via microwave-assisted [2 + 2 + 2] cyclotrimerization reactions in the presence of nickel and cobalt catalysts [38]. First, they employed diyne 15 in the reaction with a series of alkynes (16) or nitriles (17) bearing a variety of functional groups including alkyl and alkene chains, hydroxy groups, and benzene and pyridine rings, to achieve the corresponding cyclotrimerization products 18 or 19 (Scheme 4). The subsequent DDQ oxidation step yielded anthracenes 20 or azaanthracenes 21 in good yields (see the representative examples 20a-d and 21a-d) [38].…”

“…For example, OLEDs fabricated with 9,10-diphenylanthracene derivatives 1 and 2 are blue light emitters [11,12], the 2,2'-bianthracene derivative 3 provides a green and fluorescent OLED [13], 2,2'-bianthracenyl (4) has been employed as an organic semiconductor in an OFET device [14], and di-nalkoxyanthracenes have gelling properties with diverse solvents, mainly alkanes and alcohols [4]. Furthermore, anthracene derivatives display useful biological activities; for instance, the anthraquinone derivatives 5 and 6 exert antimicrobial and antiinflammatory activity, respectively (Figure 1) [15,16].…”

Total Synthesis and Determination of the Absolute Configuration of Parimycin

“…With 14 in hand, the stage was now set to complete the total synthesis of parimycin. This was achieved through the deprotection of the remaining methyl ethers in 14 with BBr 3 and subsequent reduction with sodium dithionite in the presence of tetra- n -butylammonium bromide (TBAB) in dichloromethane/H 2 O (2:1) to afford (±)-parimycin ( 1 ) in 34% overall yield from 3 . The 1 H nuclear magnetic resonance (NMR) spectral data of 1 were in good agreement with those reported for the natural product…”