Design, synthesis, crystal structure and biological evaluation of novel 4-arylaminoquin- azoline derivatives as potent cytotoxic agents

ABSTRACT. A series of novel 4-arylaminoquinazoline derivatives were synthesized by five-step reactions, the structure was characterized by IR, 1H NMR, MS and single crystal X-ray diffraction. The result of 5aX crystal was as follows: the crystal belongs to the monoclinic system, space group P21/c with a = 12.3637(4) Å, b = 12.7902(2) Å, c = 13.2240(5) Å, α = 90°, β = 117.030(5)°, γ = 90°, V = 1862.75(12) Å3, Z = 2, F(000) = 804.0, µ = 0.095        mm-1, S = 1.039, R = 0.0569, wR = 0.1535 for 8417 observed reflections with I > 2σ(I). The compound 5cX exhibited an excellent inhibitory effect on the cell line A549 (IC50 ＜ 2.5 µM) and the drug-resistant cell line H1975 (IC50 ＜ 2.5 µM) by the biological activitywhich were superior to the positive control Zorifertinib (against A549: IC50 = 31.08 µM; against H1975: IC50 = 64.17 µM). Molecular docking revealed that the better inhibitory activity of compound 5cX was owing to the combining EGFRWT and EGFRL858R/T790M by hydrogen bonding. The physicochemical properties of the compounds were predicted by using ADME data analysis, and the results showed that the compounds all obeyed Lipinski's five rules.   KEY WORDS: Quinazoline derivatives, Synthesis, X-ray diffraction, Antitumor activity Bull. Chem. Soc. Ethiop. 2023, 37(5), 1171-1183.                                                            DOI: https://dx.doi.org/10.4314/bcse.v37i5.10