Research Article

Novel N-(3-ethynyl Phenyl)-6,7-bis(2-methoxyethoxy)Quinazoline-4-amine Derivatives: Synthesis, Characterization, Anti-cancer Activity, <i>In-silico</i> and DFT Studies

Author(s):

Amitananda Dash, Guruswamy Vaddamanu, Raja Karreddula, Surya Surendra Babu Manubolu, Pavana Kumari G.* and Naveen Mulakayala*   Pages 514 - 532 ( 19 )

Abstract:

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 ¹H NMR, ¹³C 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 in vitro 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 in-vitro study results were found to be in agreement with the predictions from in-silico data. The selected molecules were further subjected to get the possible mechanism of action against different cancer cells.

Keywords:

Erlotinib, synthesis, anti-cancer activity, NCI-60, docking studies, protein-ligand interaction, DFT studies.

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