Design and Synthesis of Bioactive Thiazole‐1 <i>H</i> ‐imidazole Based Novel Framework: PEG‐400 Mediated Synthesis and Cytotoxicity in NSCLC and Breast Cancers

Abstract A successful, environmentally acceptable, and simple process has been demonstrated for one‐pot synthesis under mild by employing polyethylene glycol 400 (PEG‐400) as a green, biodegradable solvent and methylene spacer. The present study explores the synthesis of novel hybrid derivatives as 2‐(2‐(3‐(1H‐imidazol‐1‐yl)benzylidene)hydrazineyl)‐4‐(substituted phenyl)thiazole (4a‐4j) in single‐step process using novel aldehydic fragment, i.e., 3‐(1 H ‐imidazol‐1‐yl)benzaldehyde (1). A library of 10, thiazole‐1 H ‐imidazole hybrids was synthesized in PEG‐400 and the structure was affirmed by IR, MS, 1 H NMR, and 13 C NMR spectral techniques. This reaction can be used for gram‐scale synthesis and does not require any transition metal, base, or ligand, and it is carried out under conditions that do not involve additives. The activity of synthesized compounds was screened against the proliferation of sixty cancer cell lines in nine cancer panels. Almost all compounds exhibited a considerable cytotoxicity activity toward most cancer cells. Among the synthesized compounds, two compounds 4c and 4 h exhibited the most potent antiproliferative activity, with a mean value of 16.67% and 20.22%, respectively. Compound 4c exhibited the highest efficacy in Leukaemia, NSCLC, Melanoma, Renal, and Breast cancer (lethality ranging from 3%–26%), while compound 4 h showed promising lethality in Leukaemia, NSCLC, and Breast cancer. These compounds (4c and 4 h) were further evaluated using molecular docking with tubulin protein (PDB code: 1SA0) and found the strongest binding affinity, as evidenced by the highest docking score and hydrogen bond energy.