Design and synthesis of some new imidazole-morpholine-1,2,4-oxadiazole hybrids as EGFR targeting in vitro anti-breast cancer agents

• Published in: Journal of molecular structure 2024-08, Vol.1310, p.138209, Article 138209
• Main Authors: Kannekanti, Praveen kumar, Nukala, Satheesh Kumar, Bandari, Srinivas, Jyothi, Mandala, Manchal, Ravinder, Thirukovela, Narasimha Swamy
• Format: Article
• Language: English
• Subjects: Imidazole; In vitro anti-breast cancer activity; Morpholine; 1,2,4-Oxadiazoles; Tyrosine kinase EGFR inhibition
• ISSN: 0022-2860
• DOI: 10.1016/j.molstruc.2024.138209

Pharmacophore hybridization strategy to get new imidazole-moprholine-1,2,4-oxadiazole hybrids (7a-7o).•Compound 7b showed greater activity against three human breast cancer cells (MCF-7, MDA-MB-231 and MDA-MB-468) than the standard drug 5-FU.•Compounds 7e, 7j and 7m displayed greater activity against MCF-7 than the 5-FU.•Compound 7b exhibited comparable inhibition against tyrosine kinase EGFR with the Erlotinib.•Molecular docking studies revealed important binding interactions of compounds 7b, 7e, 7j and 7m with EGFR (pdb id 4HJO).•Compounds 7b, 7e, 7j and 7m have encouraging binding energies and inhibition constants as compared to Erlotinib. Herein, we synthesized some new imidazole-moprholine-1,2,4-oxadiazoles (7a-7o) and characterized their structures using 1H NMR, 13C NMR, ESI-mass and CHN analyses techniques. All the compounds were further evaluated for their in vitro anti-proliferative activity against three human breast cancer cell lines like MCF-7, MDA-MB-231 and MDA-MB-468 and results revealed that compound 7b showed greater activity against three breast cancer cells than the standard drug 5-Fluorouracil (5-FU) with IC50 values