Novel N-(3-ethynyl Phenyl)-6,7-bis(2-methoxyethoxy)Quinazoline-4-amine Derivatives: Synthesis, Characterization, Anti-cancer Activity, and DFT Studies.

Background: Cancer is one of the most common reasons for mortality in the world. A continuous effort to develop effective anti-cancer drugs with minimum side effects has become necessary. The use of small-molecule drugs has revolutionized cancer research by inhibiting cancer cell survival and proliferation. Quinazolines are a class of bioactive heterocyclic compounds with active pharmacophores in several anti-cancer drugs. Such small molecule inhibitors obstruct the significant signals responsible for cancer cell development, thus blocking these cell signals to prevent cancer development and spread.

Objective: In the current study, novel quinazoline derivatives structurally similar to erlotinib were synthesized and explored as novel anti-cancer agents.

Methods: All the synthesized molecules were confirmed by spectroscopic techniques like H NMR, C NMR, and ESI-MS. Various techniques were applied to study the protein-drug interaction, DFT analysis, Hirshfeld surface, and target prediction. The molecules were screened for their anti-cancer properties against 60 human tumor cell lines. The growth inhibitory properties of a few compounds were studied against the MCF7 breast cancer cell line.

Results: The activity of compounds 9f, 9o, and 9s were found to be active. However, compound 9f is more active when compared with other compounds.

Conclusion: Some synthesized compounds were active against different cancer cell lines. The study results were found to be in agreement with the predictions from data. The selected molecules were further subjected to get the possible mechanism of action against different cancer cells.