Synthesis and anticancer activities of fatty acid analogs of podophyllotoxin.
Derivatives of podophyllotoxin were prepared by coupling 10 FA with the C4-alpha-hydroxy function of podophyllotoxin. The coupling reactions between FA and podophyllotoxin were carried out by dicyclohexylcarbodiimide in the presence of a catalytic amount of dimethylaminopyridine to produce quantitative yields of desired products. FA incorporated were the following: 10-hydroxydecanoic, 12-hydroxydodecanoic, 15-hydroxypentadecanoic, 16-hydroxyhexadecanoic, 12-hydroxyoctadec-Z-9-enoic, eicosa-Z-5,8,11,14-tetraenoic, eicosa-Z-8,11, 14-trienoic, eicosa-Z-11,14-dienoic, eicosa-Z-11-enoic, and eicosanoic acids. Spectroscopic studies confirmed the formation of the desired products. New molecules were investigated for their in vitro anticancer activity against a panel of human cancer cell lines including SK-MEL, KB, BT-549, SK-OV-3 (solid tumors), and HL-60 (human leukemia) cells. Most of the analogs were cytotoxic against cancerous cells, whereas no effect was observed against normal cells, unlike the parent compound podophyllotoxin, the use of which is limited due to its severe side effects.
Mustafa
Jamal
J
National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, Mississippi 38677, USA.
Khan
Shabana I
SI
Ma
Guoyi
G
Walker
Larry A
LA
Khan
Ikhlas A
IA
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D011034:Podophyllotoxin