Harnessing molecular hybridization approach to discover novel quinoline EGFR-TK inhibitors for cancer treatment.
Noha RyadAyman Abo ElmaatyIbrahim M IbrahimAli Hassan Ahmed MaghrabiMaryam Abdulrahman Yahya AlahdalRasha Mohammed SaleemIslam ZakiLina M A Abdel GhanyPublished in: Future medicinal chemistry (2024)
Aim: Using molecular hybridization approach, novel 18 quinoline derivatives ( 6a-11 ) were designed and synthesized as EGFR-TK inhibitors. Materials & methods: The antiproliferative activity was assessed against breast (MCF-7), leukemia (HL-60) and lung (A549) cancer cell lines. Moreover, the most active quinoline derivatives ( 6d and 8b ) were further investigated for their potential as EGFR-TK inhibitors. In addition, cell cycle analysis and apoptosis induction activity were conducted. Results: A considerable cytotoxic activity was attained with IC 50 values spanning from 0.06 to 1.12 μM. Besides, the quinoline derivatives 6d and 8b displayed potent inhibitory activity against EFGR with IC 50 values of 0.18 and 0.08 μM, respectively. Conclusion: Accordingly, the afforded quinoline derivatives can be used as promising lead anticancer candidates for future optimization.
Keyphrases
- cell cycle
- molecular docking
- small cell lung cancer
- epidermal growth factor receptor
- tyrosine kinase
- single molecule
- structure activity relationship
- cell proliferation
- oxidative stress
- bone marrow
- endoplasmic reticulum stress
- cell death
- squamous cell carcinoma
- papillary thyroid
- molecular dynamics simulations
- machine learning
- risk assessment
- big data
- anti inflammatory
- nucleic acid
- atomic force microscopy
- lymph node metastasis