Anticancer Activity of Chitosan, Chitosan Derivatives, and Their Mechanism of Action

Table 1

Synthetic routes and activity of chitosan derivatives as anticancer agent.

S. No.	Compound	Method of synthesis	Test	Outcome	Year	Ref.
1	2-Phenyl hydrazine (or hydrazine) thiosemicarbazone chitosan	Reaction of 2-phenylhydrazine (or hydrazine) dithiocarboxylate intermediate with chitosan in DMSO.	Superoxide radical scavengingassay in vitro.	Higher superoxide radical scavenging effect than chitosan.	2010	[39]
2	Chitosan copper(II) complex	Reaction of chitosan with 1% acetic acid containing copper sulfate in 1:0.4 molar ratio of chitosan to CuSO4.5H2O, neutralized by dilute ammonia solution.	Cell proliferation assays after adding WST-8 and 1-methoxy-PMS in chitosan -copper cell well in vitro.	Inhibition of the proliferation of HeLa and 293 cells.	2006	[42]
3	CMCS	Reaction of chloroacetic acid with NaOH alkalized chitosan (Chen and Park)	Antitumor angiogenesis effects in vitro through MTT, and transwell migration assay in HUVECs and in vivo test in H22 bearing mice.	Significant inhibition of the migration of HUVECs in vitro and H22 growth inhibition in vivo.	2003; 2015	[55]; [45]
4	Chitosan-thymine conjugate	Reaction of chitosan with thymine-1-yl-acetic acid followed by acylation.	Cellular cytotoxicity, proliferation and viability assays with HepG2 culture in DMEM with fetal bovine serum in suitable seeding conditions.	In vitro inhibition of human HepG2 proliferation in a dose-dependent manner.	2012	[46]
5	SCS and SBCS	SCS from Sulphonylation of chitosan and SBCS from Schiff’s base reaction with benzaldehyde followed by sulphonylation.	MCF-7 cells culture in DMEM in heat -inactivated fetal bovine, growth inhibition study, western blot and cell apoptosis analysis.	Significant induction of MCF-7 cells apoptosis and inhibition of MCF-7 cells proliferation in vitro.	2011	[47]
6	Suc-Chi	Reaction of succinic anhydride with DAC-90 in DMSO followed by precipitation with aq. NaOH at pH 5	Intraperitoneal administration after the intraperitoneal tumor inoculation in mice models.	Increase in antitumor activity with increase in dose in L1210 in vivo.	2005; 2006; 1993	[48]; [71]; [72]
7.	G-Chi	Reaction of ethylene glycol with chitosan	The intravenous in vivo study of fluorescein thiocarbamyl-G-Chi (G-Chi-FTC) in normal mice.	Localization in kidney and longer retention in the blood circulation	2001; 2005	[73]; [48]
			Intraperitoneal administration of G-Chi-MMC to mice bearing P388 leukemia.	Decrease in toxic side effects	2001; 2005	[73]; [48]
8.	Furanoallocolchicinoid –chitosan	Reaction of furanoallocolchicinoid with succinic anhydride in tetrahydrofuran under an inert atmosphere followed by the extraction with ethyl acetate, addition of chitosan in the presence of acetic acid (pH 6) and methanol, stirring with EDC and NHS, drying and washing with toluene.	In vivo study of the compound in Wnt-1 breast tumor bearing mice.	Decrease in side effects, sequestering of colchicine drug from noncancer cells and increase in its biodistribution in cancer cells, more inhibition of tumor growth than chitosan.	2016; 2011; 2015; 2014	[49]; [74]; [75]; [76]
9.	PPC	Graft copolymerization of chitosan with pyrrole	In vitro release of PPC nanoparticles in EAC cells at pH 2.	Enhanced in vitro inhibitory effect of PPC silver nanocomposite on EAC cells proliferation after loading of 3-amino -2-phenyl 4(3H)-quinazolinone.	2017; 2017	[50]; [51]