Antitumor agents 251: synthesis, cytotoxic evaluation, and structure-activity relationship studies of phenanthrene-based tylophorine derivatives (PBTs) as a new class of antitumor agents.
Polar phenanthrene-based tylophorine derivatives (PBTs) were designed, synthesized and evaluated as potential antitumor agents. These compounds contain a core phenanthrene structure and can be synthesized efficiently in excellent yield. The newly synthesized PBTs were evaluated for cytotoxic activity against the A549 human cancer cell line. Among them, N-(2,3-methylenedioxy-6-methoxy-phenanthr-9-ylmethyl)-L-2-piperidinemethanol (34) and N-(2,3-methylenedioxy-6-methoxy-phenanthr-9-ylmethyl)-5-aminopentanol (28) showed the highest potency with IC50 values of 0.16 and 0.27 microM, respectively, which are comparable to those of currently used antitumor drugs. A structure-activity relationship (SAR) study was also explored to facilitate the further development of this new compound class.
Wei
Linyi
L
Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
Brossi
Arnold
A
Kendall
Ross
R
Bastow
Kenneth F
KF
Morris-Natschke
Susan L
SL
Shi
Qian
Q
Lee
Kuo-Hsiung
KH
D000470:Alkaloids / Q000138:chemical synthesis* / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007202:Indicators and Reagents; D007212:Indolizines / Q000138:chemical synthesis* / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D010616:Phenanthrenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D007202:Indicators and Reagents; D007212:Indolizines; D010616:Phenanthrenes; C004218:tylophorine