| Autor: |
Karki SS; College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5C9, Canada.; Department of Pharmaceutical Chemistry, KLE College of Pharmacy-Bengaluru (A Constituent Unit of KAHER-Belagavi), Bengaluru 560010, Karnataka, India., Das U; College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5C9, Canada., Balzarini J; Rega Institute of Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, Belgium., De Clercq E; Rega Institute of Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, Belgium., Sakagami H; Mekei University Research Institute of Odontology (M-RIO), School of Dentistry, Meikai University, Sakado 350-0238, Saitama, Japan., Uesawa Y; Department of Medical Molecular Informatics, Meiji Pharmaceutical University, Tokyo 204-858, Japan., Roayapalley PK; College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5C9, Canada., Dimmock JR; College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5C9, Canada. |
| Abstrakt: |
Background: A series of 3,5-benzylidene-4-piperidones, 1a - n , were prepared to evaluate the hypothesis that the placement of different groups in the ortho-location of the aryl rings led to compounds with greater cytotoxic potencies than structural analogs. Methods: The bioevaluation of 1a - n was undertaken using human Molt/4C8 and CEM cells as well as murine L1210 cells. Correlations were sought between the interplanar angles θ A and θ B and the cytotoxic potencies. A QSAR analysis was also undertaken. In order to evaluate whether these compounds demonstrated greater toxicity to neoplasms than non-malignant cells, 1a - n were evaluated against HSC-2, HSC-3, HSC-4 and HL60 neoplasms as well as non-malignant HGF, HPC and HPLF cells. Results: A positive correlation was noted between the interplanar angle θ A of one of the aryl rings and the adjacent olefinic linkage with IC 50 values in the Molt4/C8 screens. The QSAR analysis revealed a positive correlation between the Hansch pi (π) value of the aryl substituents and the IC 50 values of the compounds towards the Molt4/C8 and CEM cells. The dienones in series 1 demonstrated higher tumor-selective toxicity towards HSC-2, HSC-3, HSC-4 and HL-60 neoplasms than HGF, HPC and HPLF cells. Conclusions: The bioevaluations revealed some support for greater cytotoxic potencies to be displayed by compounds having ortho-substituents. |
