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Updated: Jul 23, 2025
Preclinical Assessment of the Bioactivity of the Anticancer Coumarin OT48 by Spheroids, Colony Formation Assays, and Zebrafish Xenografts
Published on: June 26, 2018
In silico screening, synthesis, characterization and biological evaluation of novel anticancer agents as potential
Ankita Sahu1, Dibyabhaba Pradhan2, Babita Veer3
1Tumor Biology, ICMR-National Institute of Pathology, New Delhi, 110029, India.
Background:
Cyclooxygenase enzyme is frequently overexpressed in various types of cancer and found to play a crucial role in poor prognosis in cancer patients. In current research, we have reported the new COX-2 inhibitors for cancer treatment using computer-aided drug design and experimental validation.
Methods:
A total of 12,795 compounds from the different databases were used to screen against the COX-2 enzyme. It perceived three new compounds with better binding affinity to the enzyme. Afterwards, physicochemical properties and in silico bioactivity were assessed for efficacy, safety, and structural features required for binding. The molecules were synthesized and confirmed by spectroscopic techniques. Later on, molecules were evaluated for their anti-cancer activity using MCF-7, MDA-MB-231 and SiHa cancer cell lines.
Results:
Compound ZINC5921547 and ZINC48442590 (4a, and 4b) reduced the MCF-7, MDA-MB-231, and SiHa cells proliferation potently than parent compounds. The PG-E2 estimation shown, both compounds act through the COX-2 PGE2 axis. Compound 4a and 4b block the cell cycle at G1-S phase and induce cancer cell death.
Conclusions:
We concluded that compounds 4a and 4b effectively promotes cancer cell death via COX-2 PGE2 axis, and further in vivo studies can be evaluated for development in both compounds as anticancer agents. The compilation of this information will help us to generate better outcome through robust computational methods. The high-quality experimental results may pave the way for identifying effective drug candidates for cancer treatment.
Insights
New drug compounds targeting cyclooxygenase-2 (COX-2) were identified using computational methods and validated experimentally. These novel COX-2 inhibitors effectively induce cancer cell death, offering potential for new cancer therapies.
Area of Science:
- Medicinal Chemistry
- Computational Drug Design
- Oncology
Background:
- Cyclooxygenase-2 (COX-2) is overexpressed in many cancers, correlating with poor patient prognosis.
- Targeting COX-2 is a strategy for cancer treatment.
Purpose of the Study:
- To identify novel COX-2 inhibitors for cancer therapy.
- To validate computationally designed compounds through experimental methods.
Main Methods:
- Screening of 12,795 compounds against the COX-2 enzyme.
- In silico assessment of physicochemical properties and bioactivity.
- Synthesis and spectroscopic confirmation of lead compounds.
- In vitro anti-cancer activity evaluation using MCF-7, MDA-MB-231, and SiHa cell lines.
Main Results:
- Two compounds (ZINC5921547 and ZINC48442590, designated 4a and 4b) demonstrated potent inhibition of cancer cell proliferation.
- Compounds 4a and 4b act via the COX-2/Prostaglandin E2 (PGE2) pathway.
- These compounds induce cancer cell death by blocking the cell cycle at the G1-S phase.
Conclusions:
- Compounds 4a and 4b effectively promote cancer cell death through the COX-2/PGE2 axis.
- Further in vivo studies are warranted for the development of these compounds as anticancer agents.
- Computational methods combined with experimental validation can accelerate the identification of effective drug candidates.
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