1. Synthesis of aspirin-curcumin mimic conjugates of potential antitumor and anti-SARS-CoV-2 properties.
- Author
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Srour AM, Panda SS, Mostafa A, Fayad W, El-Manawaty MA, A F Soliman A, Moatasim Y, El Taweel A, Abdelhameed MF, Bekheit MS, Ali MA, and Girgis AS
- Subjects
- Antineoplastic Agents metabolism, Antineoplastic Agents pharmacology, Antiviral Agents metabolism, Antiviral Agents pharmacology, COVID-19 pathology, COVID-19 virology, Cell Cycle Checkpoints drug effects, Cell Line, Tumor, Cell Survival drug effects, Cyclooxygenase 1 chemistry, Cyclooxygenase 1 metabolism, Cyclooxygenase 2 chemistry, Cyclooxygenase 2 metabolism, Drug Design, ErbB Receptors antagonists & inhibitors, ErbB Receptors metabolism, Humans, Inhibitory Concentration 50, Molecular Docking Simulation, Protein Binding, SARS-CoV-2 drug effects, SARS-CoV-2 isolation & purification, Vascular Endothelial Growth Factor Receptor-2 antagonists & inhibitors, Vascular Endothelial Growth Factor Receptor-2 metabolism, Antineoplastic Agents chemistry, Antiviral Agents chemistry, Aspirin chemistry, Curcumin chemistry
- Abstract
Series of piperidone-salicylate conjugates were synthesized through the reaction of 3E,5E-bis(arylidene)-4-piperidones with the appropriate acid chloride of acetylsalicylate in the presence of triethylamine. All the synthesized conjugates reveal antiproliferative properties against A431 (squamous skin) cancer cell line with potency higher than that of 5-fluorouracil. Many of the synthesized agents also exhibit promising antiproliferative properties against HCT116 (colon) cancer cell line, of which 5o and 5c are the most effective with 12.9, 9.8 folds potency compared with Sunitinib. Promising activity is also shown against MCF7 (breast) cancer cell line with 1.19, 1.12 folds relative to 5-fluorouracil. PI-flow cytometry of compound 5c supports the arrest of cell cycle at G1-phase. However, compound 5o and Sunitinib arrest the cell cycle at S-phase. The synthesized conjugates can be considered as multi-targeted tyrosine kinase inhibitors due to the promising properties against VEGFR-2 and EGFR in MCF7 and HCT116. CDOCKER studies support the EGFR inhibitory properties. Compounds 5p and 5i possessing thienylidene heterocycle are anti-SARS-CoV-2 with high therapeutic indices. Many of the synthesized agents show enhanced COX-1/2 properties than aspirin with better selectivity index towards COX-2 relative to COX-1. The possible applicability of the potent candidates discovered as antitumor and anti-SARS-CoV-2 is supported by the safe profile against normal (non-cancer, RPE1 and VERO-E6) cells., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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