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09:20
Preclinical Assessment of the Bioactivity of the Anticancer Coumarin OT48 by Spheroids, Colony Formation Assays, and Zebrafish Xenografts
Published on: June 26, 2018
Oxindole-Coumarin Hybrids With Broad-Spectrum Anticancer Activity: Apoptosis Induction and Selective CA IX/XII
Hend I Abdelaal1, Abdalla R Mohamed1, Mohamed R Elnagar2,3
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo, Egypt.
Drug Development Research
|June 10, 2025
Summary
Novel oxindole-coumarin hybrids demonstrate significant anticancer potential by inducing apoptosis. Compound 6e shows promising tumor suppression with a favorable safety profile, inhibiting key carbonic anhydrase enzymes.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Cancer Biology
Background:
- Oxindole and coumarin scaffolds are explored for therapeutic potential.
- Scaffold hybridization aims to enhance biological activity.
- Carbonic anhydrases (CAs) are targets in cancer therapy.
Purpose of the Study:
- To synthesize and evaluate oxindole-coumarin hybrids for anticancer and carbonic anhydrase inhibitory activities.
- To investigate the mechanism of action for potent anticancer compounds.
- To assess the selectivity and safety profile of the synthesized compounds.
Main Methods:
- Scaffold hybridization of oxindole and coumarin lead compounds.
- In vitro anticancer screening against NCI 60 cell line panel.
- Apoptosis assays including BAX/BCL-2 ratio and caspase-9 expression.
- Carbonic anhydrase inhibition assays (CA IX, XII, I, II).
- Cytotoxicity assessment against normal cell lines (Vero).
Main Results:
- Two hybrids, 6c and 6e, exhibited broad-spectrum anticancer activity with low micromolar GI50 values.
- Compounds 6c and 6e induced apoptosis via increased BAX/BCL-2 ratio and caspase-9 activation.
- Compound 6e showed potent inhibition of tumor-associated carbonic anhydrase IX and XII (KIs = 1.8 and 2.1 μM).
- Compound 6e displayed minimal cytotoxicity to normal Vero cells and was inactive against cytosolic CA I and II.
Conclusions:
- Scaffold hybridization successfully enhanced anticancer activity of oxindole-coumarin compounds.
- Compound 6e demonstrates potent anticancer effects through apoptosis induction and CA IX/XII inhibition.
- Compound 6e possesses a favorable safety profile, suggesting potential as a chemotherapeutic agent.
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