Synthesis and Biological Activity Screening of Newly Synthesized Trimethoxyphenyl-Based Analogues as Potential Anticancer Agents.
Tarfah Al-WarhiMatokah AbualnajaOla A Abu AliFayez AlthobaitiFahad AlharthiFahmy G ElsaidAli A ShatiEman FayadDoaa ElghareebAli Hussein Abu AlmaatyIslam ZakiPublished in: Molecules (Basel, Switzerland) (2022)
A group of novel trimethoxyphenyl (TMP)-based analogues were synthesized by varying the azalactone ring of 2-(3,4-dimethoxyphenyl)-4-(3,4,5-trimethoxybenzylidene)oxazolone 1 and characterized using NMR spectral data as well as elemental microanalyses. All synthesized compounds were screened for their cytotoxic activity utilizing the hepatocellular carcinoma (HepG2) cell line. Compounds 9 , 10 and 11 exhibited good cytotoxic potency with IC 50 values ranging from 1.38 to 3.21 μM compared to podophyllotoxin (podo) as a reference compound. In addition, compounds 9 , 10 and 11 exhibited potent inhibition of β-tubulin polymerization. DNA flow cytometry analysis of compound 9 shows cell cycle disturbance at the G2/M phase and a significant increase in Annexin-V-positive cells compared with the untreated control. Compound 9 was further studied regarding its apoptotic potential in HepG2 cells; it decreased the level of MMP and Bcl-2 as well as boosted the level of p53 and Bax compared with the control HepG2 cells.
Keyphrases
- cell cycle
- flow cytometry
- induced apoptosis
- cell proliferation
- molecular docking
- cell death
- cell cycle arrest
- magnetic resonance
- anti inflammatory
- human health
- high resolution
- oxide nanoparticles
- optical coherence tomography
- solid state
- circulating tumor
- endoplasmic reticulum stress
- signaling pathway
- cell free
- big data
- structure activity relationship
- climate change
- molecular dynamics simulations
- nucleic acid