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- W3081848457 endingPage "104218" @default.
- W3081848457 startingPage "104218" @default.
- W3081848457 abstract "Abstract Thalidomide and its analogs are immunomodulatory drugs that inhibit the production of certain inflammatory mediators associated with cancer. In the present work, a new series of thalidomide analogs was designed and synthesized to obtain new effective antitumor immunomodulatory agents. The synthesized compounds were evaluated for their cytotoxic activities against a panel of four cancer cell lines (HepG-2, HCT-116, PC3 and MCF-7). Compounds 33h, 33i, 42f and 42h showed strong potencies against all tested cell lines with IC50 values ranging from 14.63 to 49.90 µM comparable to that of thalidomide (IC50 values ranging from 32.12 to 76.91 µM). The most active compounds were further evaluated for their in vitro immunomodulatory activities via estimation of human tumor necrosis factor alpha (TNF-α), human caspase-8 (CASP8), human vascular endothelial growth factor (VEGF), and nuclear factor kappa-B P65 (NF-κB P65) in HCT-116 cells. Thalidomide was used as a positive control. Compounds 33h and 42f showed a significant reduction in TNF-α. Furthermore, compounds 33i and 42f exhibited significant elevation in CASP8 levels. Compounds 33i and 42f inhibited VEGF. In addition, compound 42f showed significant decrease in levels of NF-κB p65. Moreover, apoptosis and cell cycle tests of the most active compound 42f, were performed. The results indicated that compound 42f significantly induce apoptosis in HCT-116 cells and arrest cell cycle at the G2/M phase." @default.
- W3081848457 created "2020-09-08" @default.
- W3081848457 creator A5015501804 @default.
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- W3081848457 creator A5091586820 @default.
- W3081848457 date "2020-11-01" @default.
- W3081848457 modified "2023-10-16" @default.
- W3081848457 title "Design, synthesis, and biological evaluation of new challenging thalidomide analogs as potential anticancer immunomodulatory agents" @default.
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- W3081848457 doi "https://doi.org/10.1016/j.bioorg.2020.104218" @default.
- W3081848457 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32932121" @default.
- W3081848457 hasPublicationYear "2020" @default.