Synthesis and Pharmacological Evaluation of 4‐Aryloxyquinazoline Derivatives as Potential Cytotoxic Agents

Abstract

In the present study, novel 4‐aryloxyquinazoline derivatives were synthesized and screened for in vitro cytotoxicity on human cancer cell lines at 10 μM. Some of the synthesized compounds displayed moderate to significant and selective cytotoxic activity against various leukemia, melanoma, ovarian, breast, and colon cancer cell lines. (E)‐3‐(3,4‐Dimethoxyphenyl)‐1‐(4‐(quinazolin‐4‐yloxy)phenyl)prop‐2‐en‐1‐one (9b) was the most potent compound among all with an average growth inhibition of 70% against leukemia cancer cell lines. The compound also produced strong inhibition (75%) of colon cancer cell lines with 42.58% lethality of HCT‐116 cell line.

Quinazoline‐chalcone hybrids as HDAC/EGFR dual inhibitors: Design, synthesis, mechanistic, and in‐silico studies of potential anticancer activity against multiple myeloma

“…Intermediates 1, [72,73] 4a-e, [74][75][76][77] 6a, 6b, [78,79] and 7a, 7b [73,80] were synthesized according to a previous procedure. Notably, intermediate 2 was prepared according to previously reported procedures, [100] however, it needs a special workup involving dilution of reaction mixture after cooling with 30 mL benzene.…”

“…The hydroxy chalcone intermediates 4a-e were synthesized by the reaction of 4-hydroxy acetophenone and the appropriate un/substituted benzaldehydes 3a-e in the presence of aqueous potassium hydroxide via aldol condensation reaction. [74][75][76][77] Then, the alkylation of the appropriate chalcones 4a-e with intermediate 2 in the presence of potassium carbonate and dimethylformamide gives the final compounds 5a-e. This latter reaction proceeds via ipso addition by the nucleophile that gives an anion with a highly delocalized charge followed by leaving of the chlorine atom of the respective 4-chloro-2methylquinazoline (2) to afford the alkoxyquinazolines (5a-e).…”