Synthesis, characterization, and anticancer activity of chitosan functionalized isatin based thiosemicarbazones, and their copper(II) complexes.

The one-pot synthetic method of condensation of isatin and 5-chloroisatin on to amino group at C2 position of the pyranose ring chitosan in chitosan thiosemicarbazide was employed to get these chitosan thiosemicarbazones (TSCs). The partial incorporation of thiosemicarbazone moiety in chitosan was shown by FT-IR and 13C NMR spectroscopic studies, powder X ray diffraction, and CHNS microanalysis. The NOS tridentate coordination behavior of TSCs with copper(II) chloride to give the square planar complexes was established by FT-IR spectroscopic data, magnetic susceptibility measurement, and EPR spectral analysis. The thermal stability of these biomaterial chitosan derivatives till the commencement of chain disruption at 200C was shown by thermal studies. As revealed by colorimetric MTT assays, the in vitro anticancer activity enhancement accorded with the functionalization of chitosan as isatin based chitosan TSCs, and NOS tridentate coordination of TSCs plus a monodentate coordination of chloride ion with copper(II) ion. Only a marginal activity difference of these compounds was observed against the tumorigenic MDCK and MCF-7 cancer cell lines, irrespective of unit molecular weight (Mw) and degree of deacetylation (DDA) of ring chitosan. The 5-chloroisatin chitosan TSCs showed better activity than isatin chitosan TSCs against both the cell lines.

Pyridine-Based NNS Tridentate Chitosan Thiosemicarbazones and Their Copper(II) Complexes: Synthesis, Characterization, and Anticancer Activity.

Chitosan-functionalized pyridine-based thiosemicarbazones and their copper(II) complexes have been found to own a substantial antiproliferative activity against the tumorigenic Madin Darby canine kidney (MDCK) and MCF-7 cancer cell lines. In the current study, chitosan oligosaccharide (CS) (87% DDA, Mw < 3000 Da) and crab shell chitosan (CCS) (67% DDA, M w 350 kDa) were functionalized as chitosan pyridine-2-thiosemicarbazones and chitosan 2-acetyl pyridine-2-thiosemicarbazones, and their copper(II) complexes were synthesized. The formation of chitosan thiosemicarbazones and their NNS tridentate behavior to give the square planar copper(II) chitosan thiosemicarbazone complexes were established by spectroscopic studies, powder X-ray diffraction, elemental analysis, and magnetic moment measurements. The thermal study showed a marked stability of these derivatives before the outset of chitosan backbone degradation at 200 °C. The colorimetric MTT assay revealed a higher activity of CS thiosemicarbazones, viz., CSTSC series (IC50 375-381 µg mL-1 in the MDCK cell line and 281-355 µg mL-1 in the MCF-7 cell line) than that of high-molecular-weight CCS thiosemicarbazones, viz., CCSTSC series (IC50 335-400 µg mL-1 in the MDCK cell line and 365-400 µg mL-1 in the MCF-7 cell line), showing an enhanced activity with a decrease in Mw and an increase in DDA of constituent chitosan, a higher activity of both of these series of thiosemicarbazones than that of their native chitosan, viz., CS (IC50 370 µg mL-1 in the MCF-7 cell line and >400 µg mL-1 in the MDCK cell line) and CCS (IC50 > 400 µg mL-1 in both cell lines), and a higher activity of the Cu-CSTSC complexes (IC50 322-342 µg mL-1 in the MDCK cell line and 278-352 µg mL-1 in the MCF-7 cell line) and Cu-CCSTSC complexes (IC50 274-400 µg mL-1 in the MDCK cell line and 231-352 µg mL-1 in the MCF-7 cell line) than that of their respective ligands.

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

Tailoring of chitosan through the involvement of its amino, acetamido, and hydroxy groups can give derivatives of enhanced solubility and remarkable anticancer activity. The general mechanism of such activity is associated with the disturbances in normal functioning of cell cycle, interference to the central dogma of biological system from DNA to RNA to protein or enzymatic synthesis, and the disruption of hormonal path to biosynthesis to inhibit the growth of cancer cells. Both chitosan and its various derivatives have been reported to selectively permeate through the cancer cell membranes and show anticancer activity through the cellular enzymatic, antiangiogenic, immunoenhancing, antioxidant defense mechanism, and apoptotic pathways. They get sequestered from noncancer cells and provide their enhanced bioavailability in cancer cells in a sustained release manner. This review presents the putative mechanisms of anticancer activity of chitosan and mechanistic approaches of structure activity relation upon the modification of chitosan through functionalization, complex formation, and graft copolymerization to give different derivatives.