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Published on: September 1, 2019
Semicarbazone Derivatives Bearing Phenyl Moiety: Synthesis, Anticancer Activity, Cell Cycle, Apoptosis-Inducing and
Abstract:
A series of semicarbazone derivatives bearing phenyl moiety were synthesized and evaluated for the vitro anticancer activities in four human cancer cell lines (human colon cancer (HT29), human neuro-blastoma (SK-N-SH), human breast cancer (MDA-MB-231), and human gastric cancer (MKN45)). Biological evaluation led to the identification of 11q and 11s, which showed excellent anticancer activities against tested cancer cell lines with IC50 values ranging from 0.32 to 1.57 µM, respectively, while exhibiting weak cytotoxicity on the normal cells (human umbilical vein endothelial cell (HUVEC)). Flow cytometric assay for cell cycle and apoptosis revealed that 11q and 11s caused an arrest in the Sub-G1 cell cycle and inhibited proliferation of cancer cells by inducing apoptosis in a dose-dependent manner. Further enzymatic assay suggested that 11q and 11s could significantly activated procaspase-3 to caspase-3. Metabolic stability study indicated that 11q and 11s showed moderate stability in vitro in human and rat liver microsomes. In view of promising pharmacological activities of 11q and 11s, which had emerged as the valuable lead for further development in the treatment for cancer.
Insights
New semicarbazone derivatives, 11q and 11s, demonstrate potent anticancer activity against multiple human cancer cell lines. These compounds induce apoptosis and cell cycle arrest, showing promise as novel cancer therapeutics with low toxicity to normal cells.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Cancer Biology
Background:
- Semicarbazone derivatives are explored for their therapeutic potential.
- Developing novel anticancer agents with improved efficacy and safety is crucial.
Purpose of the Study:
- To synthesize and evaluate novel semicarbazone derivatives for anticancer activity.
- To identify lead compounds for further cancer drug development.
Main Methods:
- Synthesis of phenyl-bearing semicarbazone derivatives.
- In vitro anticancer screening against human cancer cell lines (HT29, SK-N-SH, MDA-MB-231, MKN45).
- Flow cytometry for cell cycle and apoptosis analysis, enzymatic assays, and metabolic stability studies.
Main Results:
- Compounds 11q and 11s exhibited potent in vitro anticancer activity (IC50: 0.32–1.57 µM) against tested cancer cells.
- 11q and 11s showed weak cytotoxicity against normal human umbilical vein endothelial cells (HUVEC).
- These compounds induced Sub-G1 cell cycle arrest and apoptosis, activating caspase-3, with moderate metabolic stability.
Conclusions:
- 11q and 11s are identified as promising lead compounds for anticancer drug development.
- The mechanism involves apoptosis induction and cell cycle arrest.
- Further preclinical development is warranted based on potent activity and favorable preliminary safety profile.
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