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

Abstract

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, M w < 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 (IC 50 375–381 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 (IC 50 335–400 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 M w 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 (IC 50 370 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 (IC 50 322–342 μg mL –1 in the MDCK cell line and 278–352 μg mL –1 in the MCF-7 cell line) and Cu-CCSTSC complexes (IC 50 274–400 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.

Bee chitosan nanoparticles loaded with apitoxin as a novel approach to eradication of common human bacterial, fungal pathogens and treating cancer

“…After the entry of chitosan nanoparticleloaded Api into the cellular environment, a direct impact on the nucleus was seen, leading to the activation of certain genes involved in the increased generation of apoptosis. The pyridine-based chitosan thiosemicarbazones and their copper (II) complexes have shown a favorable structure for inhibiting the growth of tumorigenic MDCK and MCF-7 cancer cell lines (Adhikari et al, 2022). A more recent in vitro study showed that the combined use of isatin and 5-chloroisatin-based chitosan thiosemicarbazones displayed anticancer activity against MDCK and MCF-7 cancer cell lines (Adhikari et al, 2023).…”

“…A more recent in vitro study showed that the combined use of isatin and 5-chloroisatin-based chitosan thiosemicarbazones displayed anticancer activity against MDCK and MCF-7 cancer cell lines (Adhikari et al, 2023). The sustained induction of apoptosis may lead to a significant reduction in the population of cancer cells, which can be achieved by the use of chitosan nanoparticles (Adhikari et al, 2022). The overall outcome was a reduction in cell viability, accompanied by the inactivation of cell division, growth promoter genes, and other virulence genes.…”

Recent Advances in Pyridine Scaffold: Focus on Chemistry, Synthesis, and Antibacterial Activities

“…Considering biological interest, a simple strategy for the preparation of pyridine-based chitosan thiosemicarbazide 45a, b was described [ 43 ]. Treatment of chitosan 44 with ammonia followed by carbon disulfide produced ammonium dithiocarbamate chitosan (ADC, 45 ).…”

Cytotoxic Activity of Schiff Bases and Their Complexes

“…2-Picoline and 5,5-dimethylbipyridine and its Cu(II) complexes cytotoxic activity was reported on MDA-MB-231 breast cancer cell line [36]. Chitosan-functionalized pyridine-based Thiosemicarbazones and their Cu(II) complexes shows antiproliferative activity against MCDK and MCF-7 cancer cell lines and their complexes shows high cytotoxic activity than ligands [37]. N-substitution in isatin thiosemicarbazones and its Cu(II) complexes MTT assays were done on A549,HeLa S3, Jurkat and IMR90 cells, its complexes exhibits more cytotoxic activity on HeLa S3 and Jurkat cell lines than cisplatin and morphological changes were observed [38].…”