Novel anti-viability ceramide analogs: design, synthesis, and structure-activity relationship studies of substituted (S)-2-(benzylideneamino)-3-hydroxy-N-tetradecylpropanamides.
A group of novel L-serinamides, substituted (S)-2-(benzylideneamino)-3-hydroxy-N-tetradecylpropanamides (3a-o) and substituted (S)-2-(benzylamino)-3-hydroxy-N-tetradecyl propanamides (4c, 4i, 4l, and 4o), were synthesized as potential anti-tumor lead compounds. In vitro cell viability assay results indicate treatment with 3a-o compounds resulted in significant inhibition of cell viability in the chemoresistant breast cancer cell line, MCF-7TN-R. Compounds 3i and 3l, both ortho-substituted analogs, show the greatest efficacy with IC50 values of 10.3 microM and 12.5 microM, respectively. The SAR analysis indicate that the imine functional group of 3a-o is critical for the cellular anti-viability effect, and the partial atomic charge (PAC) value of imine C atom is a valuable structural parameter for predicting the activity of these ceramide analogs.
Liu
Jiawang
J
Department of Chemistry, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA.
Antoon
James W
JW
Ponnapakkam
Adharsh
A
Beckman
Barbara S
BS
Foroozesh
Maryam
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002518:Ceramides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002518:Ceramides