Dec 6, 2017

Cytotoxicity, molecular modeling, cell cycle arrest, and apoptotic induction induced by novel tetrahydro-[1,2,4]triazolo[3,4-a]isoquinoline chalcones

European Journal of Medicinal Chemistry
Magda F MohamedIsmail Abdelshafy Abdelhamid

Abstract

Novel tetrahydro-[1,2,4]triazolo[3,4-a]isoquinolin-3-yl)-3-arylprop-2-en-1-one derivatives were synthesized and their structures were confirmed by different spectral tools. Cytotoxicity test revealed that some compounds exhibited strong to moderate effect, while others showed weak action against different cancer cell lines (MCF7, A549, HCT116, and Hepg2). Breast carcinoma revealed higher sensitivity toward all derivatives especially compounds 5 and 8 which offered the lowest IC50 values (50.05, and 27.15 μg/ml) respectively, relative to the positive control 5-fluorouracil (5-FU) (IC50 = 178 μg/ml). In addition, the two compounds exhibited less toxic effect toward normal melanocytes (HFB4). Several theoretical and experimental studies were done to reveal the molecular mechanisms that control breast carcinoma metastasis using the two promising novels 5 and 8. Docking simulation studies against the two proteins EGFR and DHFR demonstrate that compound 8 showed higher binding affinity toward the two proteins more than compound 5, suggesting that trimethoxy groups may be responsible for this higher activity through the formation of five hydrogen bonding with the active domain (4r3r) and other four interactions with the active domain ...Continue Reading

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Mentioned in this Paper

Interstitial Collagenase
Cell Cycle Progression
Real-Time Polymerase Chain Reaction
EGFR
Melanocyte
Antineoplastic Agents
Derivatives
Cytotoxicity Assay
Apoptosis, Intrinsic Pathway
Fluorouracil

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