Novel indole-based scaffolds: Design, synthesis, molecular modeling, and anti-proliferative evaluation
Reham A Mohamed-Ezzat1, Aisha A K Al-Ashmawy2, Aladdin M Srour3
1Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Cairo, Egypt. reham_amgad_2010@yahoo.com.
BMC Chemistry
|April 9, 2026
Summary
Novel indole-based compounds were synthesized and tested for anti-cancer properties. Compound 8a showed significant anti-proliferative activity against multiple cancer cell lines, indicating potential as a new anticancer drug.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Cancer Research
Background:
- Indole scaffolds are recognized for their diverse biological activities.
- Cyclin-dependent kinase 2 (CDK-2) is a validated target in cancer therapy.
- Molecular hybridization is a strategy to develop novel drug candidates.
Purpose of the Study:
- To design and synthesize novel indole-based compounds as potential CDK-2 inhibitors.
- To evaluate the anti-proliferative and cytotoxic activities of these compounds against the NCI-60 cancer cell line panel.
- To assess the drug-likeness and ADME properties of the synthesized compounds.
Main Methods:
- Design and synthesis of indole-sulfonate and indole-aspirin mimic conjugates.
- Cytotoxicity screening of compounds against the NCI-60 cell line panel at 10 µM.
- In silico drug likeness and ADME prediction studies.
- Molecular modeling simulation of compound 8a with CDK-2.
Main Results:
- Compound 8a demonstrated potent anti-cancer activity with sub-micromolar GI50 values across various cancer cell lines.
- Leukemia, melanoma, CNS cancer, ovarian cancer, and non-small cell lung cancer cell lines were particularly sensitive to compound 8a.
- In silico studies predicted favorable drug likeness and ADME profiles for the compounds.
- Molecular modeling suggested potential for compound 8a as an in vitro CDK-2 inhibitor.
Conclusions:
- The novel indole-sulfonate and indole-aspirin mimic conjugates show promise as anticancer agents.
- Compound 8a is a lead candidate for further development as a CDK-2 inhibitor.
- Optimization of these indole-based scaffolds could lead to new therapeutic options for cancer treatment.
