Synthesis and anticancer activity of benzyloxybenzaldehyde derivatives against HL-60 cells

• Published in: Bioorganic & medicinal chemistry Vol. 13; no. 5; pp. 1537 - 1544
• Main Authors: Lin, Chin-Fen, Yang, Jai-Sing, Chang, Chiung-Yun, Kuo, Sheng-Chu, Lee, Miau-Rong, Huang, Li-Jiau
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.03.2005; Elsevier Science
• Subjects: Anticancer activity; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Benzaldehydes - chemical synthesis; Benzaldehydes - chemistry; Benzaldehydes - pharmacology; Benzyloxybenzaldehyde derivatives; Biological and medical sciences; Cell Cycle - drug effects; General aspects; HL-60 Cells; Humans; Medical sciences; Membrane Potentials - drug effects; Mitochondria - drug effects; Mitochondria - physiology; Pharmacology. Drug treatments; Spectrum Analysis; HL-60 cells; Benzyloxybenzaldehyde derivatives; Anticancer activity; Apoptosis; Antineoplastic agent; Human; Leukemia; Aldehyde; In vitro; HL60 cell line; Mitochondria; Cell line; Structure activity relation; G2 Phase; Membrane potential; Chemical synthesis; Antimitotic; Tumor cell; Benzaldehyde derivatives
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2004.12.026

[Display omitted] A series of benzyloxybenzaldehyde derivatives were prepared and tested against the HL-60 cell line for anticancer activity. Preliminary structure–activity relationships were established. It was discovered that 2-(benzyloxy)benzaldehyde ( 17), 2-(benzyloxy)-4-methoxybenzaldehyde ( 26), 2-(benzyloxy)-5-methoxybenzaldehyde ( 27), 2-(benzyloxy)-5-chlorobenzaldehyde ( 28), 2-[(3-methoxybenzyl)oxy]benzaldehyde ( 29), 2-[(2-chlorobenzyl)oxy]benzaldehyde ( 30), and 2-[(4-chlorobenzyl)oxy]benzaldehyde ( 31) exhibited significant activity at 1–10 μM. Among them, compound 29 was the most potent one. The morphological assessment and DNA fragmentation analysis indicated that these compounds arrested cell cycle progression at G2/M phase and induced cell apoptosis. They resulted in the loss of mitochondrial membrane potential after 12 h of treatment.