Design, synthesis and structure-activity relationship studies of novel spirochromanone hydrochloride analogs as anticancer agents.
Surendar ChittiSravani PulyaAdinarayana NandikollaTarun Kumar PatelBanoth Karan KumarSankaranarayanan MurugesanBalaram GhoshKondapalli Venkata Gowri Chandra SekharPublished in: Future medicinal chemistry (2022)
Aim: Literature reports suggest spirochromanone derivatives exhibit anticancer activity. Methodology: The authors designed and synthesized 18 spirochromanone derivatives ( Csp 1-18 ). The compounds were characterized and evaluated for anticancer activity against human breast cancer (MCF-7) and murine melanoma (B16F10) cell lines. Results: The anticancer activity ranged from 4.34 to 29.31 μm. The most potent compounds, Csp 12 and Csp 18 , were less toxic against the human embryonic kidney (HEK-293) cell line and ∼ two/∼fourfold selective toward MCF-7 than B16F10 in comparison to the reference, BG-45 . Csp 12 caused 28.6% total apoptosis, leading to significant cytotoxicity, and arrested the G2 phase of the cell cycle in B16F10 cells. A molecular docking study of Csp 12 exhibited effective binding at the active site of the epidermal growth factor receptor kinase domain. Conclusion: This study highlights the importance of spirochromanones as anticancer agents.
Keyphrases
- molecular docking
- cell cycle
- epidermal growth factor receptor
- structure activity relationship
- endothelial cells
- cell cycle arrest
- tyrosine kinase
- systematic review
- breast cancer cells
- cell proliferation
- oxidative stress
- advanced non small cell lung cancer
- molecular dynamics simulations
- cell death
- emergency department
- young adults
- pluripotent stem cells
- dna binding
- pi k akt
- anti inflammatory