35486-69-2Relevant academic research and scientific papers
Synthesis and biological evaluation of pyranoisoflavone derivatives as anti-inflammatory agents
Wei, Zhe,Yang, Youzhe,Xie, Caifeng,Li, Chunyan,Wang, Guangcheng,Ma, Liang,Xiang, Mingli,Sun, Jian,Wei, Yuquan,Chen, Lijuan
, p. 172 - 183 (2014/07/21)
In this paper, barbigerone (1a) and its twenty-seven related structural analogues were synthesized via complementary synthetic routes and their anti-inflammatory effects on the expression of TNF-α in LPS-stimulated splenocytes were evaluated. Among these compounds, 1a, 1d, 1f and 1g were found to remarkably inhibit TNF-α production. Furthermore, 1g showed the most potent and dose-dependent manner inhibitory effect on TNF-α release, with better IC50 value (3.58 μM) than barbigerone (8.46 μM). Oral administration of 1g at 20 mg/kg/day for two weeks obviously demonstrated protective effect in adjuvant-induced arthritis models as evaluated by clinical score of paws, and histological examination of joint tissues from rats. Mechanism studies on mRNA and protein level suggested that 1g inhibited the TNF-α production via depressing TNF-α converting enzyme (TACE) mRNA expression. In conclusion, these data show 1g with potential therapeutic effects as an anti-inflammatory agent.
Anti-AIDS agents. 60. Substituted 3′R,4′R-di-O-(-)-camphanoyl- 2′,2′-dimethyldihydropyrano[2,3-f]chromone (DCP) analogues as potent anti-HIV agents
Yu, Donglei,Chen, Chin-Ho,Brossi, Arnold,Lee, Kuo-Hsiung
, p. 4072 - 4082 (2007/10/03)
Synthesis of positional isomers is a commonly used technique in drug design. Accordingly, based on prior SAR studies of 3′R,4′R-di-O-(S)- camphanoyl-(+)-cis-khellactone (DCK, 1) analogues, a series of mono- and disubstituted chromone derivatives of 3′R,4′R-di-O-(-)camphanoyl- 2′,2′-dimethyldihydropyrano[2,3-f]chromone (DCP, 4) were designed and synthesized. Together with 1 and 4-methyl DCK (2), all newly synthesized DCP analogues (4-21) were screened for anti-HIV-1 activity against a non-drug-resistant strain in H9 lymphocytes and a multiple reverse transcriptase (RT) inhibitor-resistant strain in the MT4 cell line. Several DCP analogues (4, 5, 7, 8, 13, and 17) exhibited extremely high anti-HIV activity in the nondrug-resistant strain assay, with EC50 values ranging from 0.00032 to 0.0057 μM and remarkable therapeutic indexes (TI) ranging from 5.6 × 103 to 1.16 × 105, which were similar to those of 2 (EC50 0.0059 μM, TI > 6.6 × 103) and better than those of 1 (EC50 0.049 μM, TI > 328). Even more promisingly, some DCP analogues also showed activity against a multi-RT inhibitor-resistant strain, HIV-1 RTMDR1, whereas most DCK analogues did not. The most significant compound was 8, with an EC50 value of 0.06 μM and TI of 718 against the multi-RT inhibitor-resistant HIV-1 strain. Compounds 9 and 10 also showed good activity with an EC50 value of 0.14 μM, and TIs of 272 and >111, respectively. 2-Ethyl DCP (8) exhibited the best anti-HIV activity in both assays. Further development of 8-related compounds as clinical trial candidates is warranted.
