Apoptosis-inducing effect of epolactaene derivatives on BALL-1 cells

• Published in: Bioorganic & medicinal chemistry Vol. 14; no. 7; pp. 2151 - 2161
• Main Authors: Kuramochi, Kouji, Matsui, Rie, Matsubara, Yasuaki, Nakai, Junko, Sunoki, Takashi, Arai, Satoshi, Nagata, Seigo, Nagahara, Yukitoshi, Mizushina, Yoshiyuki, Ikekita, Masahiko, Kobayashi, Susumu
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.04.2006; Elsevier Science
• Subjects: Antineoplastic agents; Apoptosis; Apoptosis - drug effects; BALL-1 cells; Biological and medical sciences; Cell Line, Tumor; Cell Survival - drug effects; Drug Screening Assays, Antitumor; Epolactaene; Epoxy Compounds - chemical synthesis; Epoxy Compounds - chemistry; Epoxy Compounds - pharmacology; General aspects; Humans; Hydrolysis; Leukemia, B-Cell - drug therapy; Medical sciences; Molecular Structure; Pharmacology. Drug treatments; Polyenes - chemical synthesis; Polyenes - chemistry; Polyenes - pharmacology; Stereoisomerism; Structure-Activity Relationship; Structure–activity relationships; Epolactaene; BALL-1 cells; Structure–activity relationships; Apoptosis; Antineoplastic agent; Leukemia; Lactam; Cytotoxicity; Structure-activity relationships; Structure activity relation; Tertiary alcohol; Bicyclic compound; Chemical synthesis; Tumor cell; Oxygen nitrogen heterocycle; Human; Aliphatic compound; Cell differentiation; Ketone; In vitro; Side chain; Cell line; Epoxide; Property structure relationship; Lipophilicity; Physicochemical properties
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2005.10.057

Epolactaene, a neuritogenic compound in human neuroblastoma SH-SY5Y, induces apoptosis in a human leukemia B-cell line, BALL-1. The apoptosis-inducing activities of 34 epolactaene derivatives, including those of the newly synthesized α-alkyl-α,β-epoxy-γ-lactam derivative and cyclopropane derivatives, were also tested. The structure–activity relationships of the epolactaene derivatives as an inducer of apoptosis are described. The α-acyl-α,β-epoxy-γ-lactam moiety as well as the hydrophobicity derived from the long alkyl side chain are both important for activity. Compound 1e displayed the strongest activity among all the synthesized compounds with an IC 50 value of 0.70 μM.