Synthesis and Characterization of Aminophosphonate Containing Chitosan Polymer Derivatives: Investigations of Cytotoxic Activity and in Silico Study of SARS-CoV-19

Abstract

Chitosan is broadly used as a biological material since of its excellent biological activities. This work describes investigations of chitosan interaction with SARS-CoV-2, which is occupied by human respiratory epithelial cells through communication with the human angiotension-converting enzyme II (ACE2). The β-chitosan derivatives are synthesized and characterized by FT-IR, nuclear magnetic resonance (1H and 13C NMR), mass spectrometry, X-ray diffraction, TGA, DSC, and elemental analysis. The β-chitosan derivatives were screened for cytotoxic activity against the HepG2 and MCF-7 (breast) cancer cell lines. Compound 1 h (GI50 0.02 µM) is moderately active against the HepG2 cancer cell line, and Compound 1c is highly active (GI50 0.01 µM) against the MCF-7 cancer cell line. In addition, chitosan derivatives (1a–1j) docking against the SARS coronavirus are found by in-silico docking analysis. The findings show that compound 1c exhibits notable inhibition ability compared with other compounds, with a binding energy value of −7.9kcal/mol. Based on the molecular docking results, the chitosan analog is proposed to be an alternative antiviral agent for SARS-CoV2.

Relationship between Structure and Antibacterial Activity of α-Aminophosphonate Derivatives Obtained via Lipase-Catalyzed Kabachnik−Fields Reaction

“…α-Aminophosphonates appear to be a very important class of organic compounds because of their potential biological activities [ 1 , 2 , 3 , 4 ]. The distinctive character of bioactive organophosphorus compounds has established their wide applicability in agricultural and medicinal chemistry [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. α-Aminophosphonates ( Figure 1 ) play a crucial role as a platform to design new drugs [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ].…”

Synthesis of Novel 1,3,4-Oxadiazole-Derived α-Aminophosphonates/α-Aminophosphonic Acids and Evaluation of Their In Vitro Antiviral Activity against the Avian Coronavirus Infectious Bronchitis Virus

“…Although both experimental and theoretical analyses have been performed for many types of molecules during the COVID-19 pandemic, to the best of our knowledge, α -aminophosphonates and α -aminophosphonic acids have not been studied by molecular docking for interactions with coronavirus main protease and papain-like protease. Nevertheless, molecular docking interactions of phosphonimidates containing chitosan moieties against protease of SARS coronavirus were analyzed and displayed remarkable binding affinity (−7.9 to −7.3 kcal/mol) [ 72 ]. On the other hand, in 2006, Wu’s group investigated the action of 58,855 compounds on inhibition of the main protease of the coronavirus and detected, through a virtual structure-based analysis, two types of effective compounds, one of which had an oxadiazole moiety [ 73 ].…”

Synthesis of Schiff Bases Based on Chitosan and Heterocyclic Moiety: Evaluation of Antimicrobial Activity

“…Chitosan has three types of reactive groups, primary amine, primary hydroxyl, and secondary hydroxyl, located at C-2, C-3, and C-6, respectively . Glucosamine’s primary amine at C-2 is the most important group among the three reactive groups for chitosan’s biological activity. , As a consequence of this, it has important applications in many different disciplines, including the biological sciences, agriculture, the development of functional foods, the treatment of wastewater, the preservation of the environment, biotechnology, and cosmetics . Chitosan exhibits various advantageous biological properties, including antimicrobial and antitumor effects. , Chitosan, a biopolymer derived from chitin, undergoes a process called deacetylation to produce d -glucosamine.…”

“… 2 Glucosamine’s primary amine at C-2 is the most important group among the three reactive groups for chitosan’s biological activity. 3 , 4 As a consequence of this, it has important applications in many different disciplines, including the biological sciences, agriculture, the development of functional foods, the treatment of wastewater, the preservation of the environment, biotechnology, and cosmetics. 5 Chitosan exhibits various advantageous biological properties, including antimicrobial and antitumor effects.…”

“… 5 Chitosan exhibits various advantageous biological properties, including antimicrobial and antitumor effects. 4 , 6 Chitosan, a biopolymer derived from chitin, undergoes a process called deacetylation to produce d -glucosamine. In our world, there are numerous organisms that possess the remarkable polysaccharide called chitin.…”