3-Alkenyl-2-oxindoles: Synthesis, antiproliferative and antiviral properties against SARS-CoV-2.

Autor: Girgis AS; Department of Pesticide Chemistry, National Research Centre, Dokki, Giza 12622, Egypt. Electronic address: girgisas10@yahoo.com., Panda SS; Department of Chemistry & Physics, Augusta University, Augusta, GA 30912, USA., Srour AM; Department of Therapeutic Chemistry, National Research Centre, Dokki, Giza 12622, Egypt., Abdelnaser A; Institute of Global Health and Human Ecology, School of Sciences and Engineering, The American University in Cairo (AUC), Cairo 11835, Egypt., Nasr S; Institute of Global Health and Human Ecology, School of Sciences and Engineering, The American University in Cairo (AUC), Cairo 11835, Egypt; Institute of Pharmacology of Natural Products & Clinical Pharmacology, Ulm University, D-89081 Ulm, Germany., Moatasim Y; Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt., Kutkat O; Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt., El Taweel A; Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt., Kandeil A; Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt., Mostafa A; Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt., Ali MA; Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt., Fawzy NG; Department of Pesticide Chemistry, National Research Centre, Dokki, Giza 12622, Egypt., Bekheit MS; Department of Pesticide Chemistry, National Research Centre, Dokki, Giza 12622, Egypt., Shalaby EM; X-Ray Crystallography Lab., Physics Division, National Research Centre, Dokki, Giza 12622, Egypt., Gigli L; Elettra-Sincrotrone Trieste, s.s. 14 Km 163.5 in Area Science Park, Basovizza (Trieste) 34149, Trieste, Italy., Fayad W; Drug Bioassay-Cell Culture Laboratory, Pharmacognosy Department, National Research Centre, Dokki, Giza, 12622. Egypt., Soliman AAF; Drug Bioassay-Cell Culture Laboratory, Pharmacognosy Department, National Research Centre, Dokki, Giza, 12622. Egypt.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2021 Sep; Vol. 114, pp. 105131. Date of Electronic Publication: 2021 Jun 30.
DOI: 10.1016/j.bioorg.2021.105131
Abstrakt: Sets of 3-alkenyl-2-oxindoles (6,10,13) were synthesized in a facile synthetic pathway through acid dehydration (EtOH/HCl) of the corresponding 3-hydroxy-2-oxoindolines (5,9,12). Single crystal (10a,c) and powder (12a,26f) X-ray studies supported the structures. Compounds 6c and 10b are the most effective agents synthesized (about 3.4, 3.3 folds, respectively) against PaCa2 (pancreatic) cancer cell line relative to the standard reference used (Sunitinib). Additionally, compound 10b reveals antiproliferative properties against MCF7 (breast) cancer cell with IC 50 close to that of Sunitinib. CAM testing reveals that compounds 6 and 10 demonstrated qualitative and quantitative decreases in blood vessel count and diameter with efficacy comparable to that of Sunitinib, supporting their anti-angiogenic properties. Kinase inhibitory properties support their multi-targeted inhibitory activities against VEGFR-2 and c-kit in similar behavior to that of Sunitinib. Cell cycle analysis studies utilizing MCF7 exhibit that compound 6b arrests the cell cycle at G1/S phase while, 10b reveals accumulation of the tested cell at S phase. Compounds 6a and 10b reveal potent antiviral properties against SARS-CoV-2 with high selectivity index relative to the standards (hydroxychloroquine, chloroquine). Safe profile of the potent synthesized agents, against normal cells (VERO-E6, RPE1), support the possible development of better hits based on the attained observations.
(Copyright © 2021. Published by Elsevier Inc.)
Databáze: MEDLINE
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