article · Drug Design Development and Therapy
A series of novel thiazolyl-pyrazoline derivatives was synthesised and evaluated as epidermal growth factor receptor inhibitors for targeted cancer therapy. In laboratory assays, these compounds demonstrated anti-proliferative effects against both A549 lung cancer and T-47D breast cancer cell lines, exhibiting stronger potency against breast cancer cells. Four specific derivatives displayed notable sub-micromolar inhibitory action against the receptor kinase, with one compound reaching potency close to that of the established drug erlotinib. Detailed cellular investigations revealed that the two most active compounds induced apoptosis and arrested the cell cycle at the sub-G1 phase in breast cancer cells. In addition, computational docking studies confirmed that these leading derivatives accommodate into the active binding pocket of the receptor in an orientation comparable to erlotinib. These findings present new small-molecule structures with potential relevance to targeted anti-tumour drug discovery.
The epidermal growth factor receptor regulates critical cellular processes, including multiplication, survival, and cell death, making it a key therapeutic target in oncology. Developing new chemical scaffolds that selectively block this receptor can provide alternative therapeutic options against lung and breast cancers, potentially expanding the range of targeted interventions available for future cancer drug development programmes.
This research represents early-stage, laboratory-based drug discovery aimed at developing new anti-tumour therapies for breast and lung cancer. Pharmaceutical companies and medicinal chemistry researchers could potentially use these chemical scaffolds as starting points for further lead optimisation and preclinical testing. However, the molecules remain at an early experimental stage, having only undergone in vitro cellular evaluations and computational docking, and are far from clinical application.
AI-generated from the published abstract. Always read the original work before citing.
Introduction: Epidermal growth factor receptor (EGFR) regulates several cell functions which include cell growth, survival, multiplication, differentiation, and apoptosis. Currently, EGFR kinase inhibitors are of increasing interest as promising targeted antitumor therapeutic agents. Methods: Different thiazolyl-pyrazoline derivatives ( 7a-o ) were synthesized and were first tested for anti-proliferative effect towards the A549 lung cancer cell line and the T-47D breast cancer cell line in MTT assay. Thereafter, thiazolyl-pyrazolines ( 7b, 7g, 7l , and 7m ) were subsequently evaluated for their PK inhibition for EGFR. Moreover, representative promising derivatives ( 7g and 7m ) in cytotoxic and PK inhibition assays were tested to investigate their impact on the apoptosis and cell cycle phases in T-47D cells in order to explore more insights into the antitumor actions of the target thiazolyl-pyrazolines. Furthermore, docking studies were accomplished to evaluate the patterns of binding of thiazolyl-pyrazolines 7b, 7g, 7l , and 7m in the EGFR active pocket (PDB ID: 1M17). Results: Testing the thiazolyl pyrazoline compounds 7a-o on A549 and T-47D cell lines showed IC 50 arrays between 3.92 and 89.03 μM, and between 0.75 and 77.10 μM, respectively. Also, the tested thiazolyl-pyrazolines ( 7b, 7g, 7l , and 7m ) demonstrated significant sub-micromolar EGFR inhibitory actions with IC 50 values 83, 262, 171 and 305 nM, respectively, in comparison to erlotinib (IC 50 =57 nM). Discussion: Generally, it was observed that the tested thiazolyl pyrazolines showed more potent antiproliferative activity toward breast cancer cells T-47D than toward lung cancer cell lines A549. In particular, thiazolyl pyrazolines 7g and 7m showed the best activity against A549 cells (IC 50 = 3.92 and 6.53 μM) and T-47D cells (IC 50 = 0.88 and 0.75 μM). Compounds 7g and 7m provoked a sub-G1 phase arrest and cell apoptosis which are in agreement with the expected outcome of EGFR inhibition. Finally, the molecular docking of 7g and 7m in the active site of EGFR revealed a common binding pattern similar to that of erlotinib which involves the accommodation of the 1,3 thiazol-4-one ring and pyrazoline ring of target compounds in the binding region of erlotinib’s quinazoline ring and anilino moiety. Keywords: antitumor, EGFR inhibitors, pyrazolo, molecular docking, breast cancer, lung cancer
This page summarises published work. The authoritative version sits with the publisher.
DOI: 10.2147/dddt.s356988
Is something wrong with this record? Report it or request removal.
Discussion
Have you built on this work, tried to replicate it, or seen it applied in practice? Share what you know. Verified researchers and MARATTO™ domain experts can open a discussion, and any member can reply. Contributions are reviewed before they appear.
No discussion yet. Open the first thread.
New to MARATTO™? Create a free account.
