Exploring the Structure-Activity Relationship of COX Inhibitors with Anticancer Effects: A Comprehensive Review.

Area of Science:

• Oncology and Pharmacology
• Medicinal Chemistry

Background:

• Chronic inflammation is linked to 15-20% of malignant tumors.
• Cyclooxygenase-2 (COX-2) plays a key role in tumorigenesis by promoting angiogenesis, inhibiting apoptosis, and increasing cancer cell invasiveness.
• COX inhibitors have shown potential in reducing cancer mortality rates.

Purpose of the Study:

• To review structure-activity relationships of molecules designed for cytotoxic activity via COX inhibition.
• To analyze classical and non-classical drug design strategies for selective COX-2 inhibitors.
• To evaluate recent advancements in anticancer drug development targeting COX-2.

Main Methods:

• Analysis of studies published between 2014 and 2024 on COX-2 inhibitors.
• Evaluation of structure-activity relationships for classical (diaryl heterocyclic) and non-classical (cyclic central scaffold) designs.
• Assessment of cytotoxic activity using cell lines (MCF-7, HCT-116, A549) and assays (MTT, CellTiter, MTS).
• Investigation of correlations between COX-2 inhibition and cancer pathways (apoptosis, HDAC, EGFR, topoisomerase).

Main Results:

• Most studies reported promising cytotoxic activity for selective COX-2 inhibitors.
• Compounds with diphenyl heterocyclic scaffolds showed enhanced COX-2 selectivity and anticancer efficacy.
• Specific derivatives demonstrated significant activity comparable to standard drugs like celecoxib and doxorubicin.
• A weak correlation between COX-2 inhibition and cytotoxicity was noted in some studies, indicating other mechanisms may be involved.

Conclusions:

• Selective COX-2 inhibitors represent a promising strategy for anticancer drug development.
• Diverse chemical structures targeting COX-2 warrant further investigation for cancer therapy.
• Continued research is needed to fully elucidate the mechanisms underlying COX-2 inhibition and cytotoxicity in cancer.