Synthesis, human topoisomerase IIα inhibitory properties and molecular modeling studies of anti-proliferative curcumin mimics
作者： Nehmedo G. Fawzy , Siva S. Panda , Walid Fayad , ElSayed M. Shalaby , Aladdin M. Srour
DOI: 10.1039/C9RA05661K
关键词:
摘要: 3,5-Bis(arylidene)-N-substituted-4-oxo-piperidine-1-carboxamides 24–51 were synthesized as curcumin mimics in a facile pathway through reaction of 3,5-bis(arylidene)-4-piperidones with the appropriate isocyanate presence triethylamine. The 3E,5E′-stereochemical configuration was conclusively supported by single crystal X-ray studies compounds 25 and 34. Most piperidinecarboxamides showed high anti-proliferative properties potency higher than that 5-fluorouracil (clinically approved drug against colon, breast skin cancers) vitro MTT bio-assay. Some them revealed at sub-micromolar values (IC50 = 0.56–0.70 μM for 29, 30 34–38 HCT116; IC50 0.64 compound A431 cell lines) promising inhibitory human DNA topoisomerase IIα. safe profile active agents RPE1 normal line may prove their selectivity towards carcinoma cells. Robust molecular models (2D-QSAR, 3D-pharmacophore) SAR validated observed bio-properties.
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