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New potential anti-SARS-CoV-2 and anti-cancer therapies of chitosan derivatives and its nanoparticles: Preparation and characterization
Institution:1. Department of Chemistry, Faculty of Pharmacy, October 6 University (O6U), October 6 City, Giza 12585, Egypt;2. Chemistry Department, Faculty of Women for Art, Science and Education, Ain Shams University, Heliopolis Post Cod. No. 11757, Cairo, Egypt;3. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt;4. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, October 6 University (O6U), October 6 City, Giza 12585, Egypt;5. Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt;6. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt;7. Department of Chemistry, Basic Science Center and Pharmaceutical Organic Chemistry College of Pharmaceutical Science & Drug Manufacturing, Misr University for Science and Technology (MUST), Al-Motamayez District, 6th of the October City 77, Egypt
Abstract:Chitosan (CS) is a biopolymer and has reactive amine/hydroxyl groups facilitated its modifications. The purpose of this study is improvement of (CS) physicochemical properties and its capabilities as antiviral and antitumor through modification with 1-(2-oxoindolin-3-ylidene)thiosemicarbazide (3A) or 1-(5-fluoro-2-oxoindolin-3-ylidene)thiosemicarbazide (3B) via crosslinking of poly(ethylene glycol)diglycidylether (PEGDGE) using microwave-assisted as green technique gives (CS-I) and (CS-II) derivatives. However, (CS) derivatives nanoparticles (CS-I NPs) and (CS-II NPs) are synthesized via ionic gelation technique using sodium tripolyphosphate (TPP). Structures of new (CS) derivatives are characterized using different tools. The anticancer, antiviral efficiencies and molecular docking of (CS) and its derivatives are assayed. (CS) derivatives and its nanoparticles show enhancement in cell inhibition toward (HepG-2 and MCF-7) cancer cells in comparison with (CS). (CS-II NPs) reveals the lowest IC50 values are 92.70 ± 2.64 μg/mL and 12.64 µ g/mL against (HepG-2) cell and SARS-CoV-2 (COVID-19) respectively and the best binding affinity toward corona virus protease receptor (PDB ID 6LU7) ?5.71 kcal / mol. Furthermore, (CS-I NPs) shows the lowest cell viability% 14.31 ± 1.48 % and the best binding affinity ?9.98 kcal/moL against (MCF-7) cell and receptor (PDB ID 1Z11) respectively. Results of this study demonstrated that (CS) derivatives and its nanoparticles could be potentially employed for biomedical applications.
Keywords:Chitosan and chitosan NP’s derivatives  COVID-19  Anticancer  Molecular docking
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