Friday, 16 October 2020

Recent Developments on the Mechanism of AntiCancer Activity of Complexes of Molecular Iodine with α-Dextrins and Polypeptides and Lithium Halogenides | Chapter 7 | Recent Progress in Microbiology and Biotechnology Vol. 3

 Some anti-infective treatments also display anti-tumor activity. In human and murine tumour cell lines, the anti-tumor function of the anti-infective drug (AID) containing a complex of molecular iodine with polypeptides, alpha-dextrins and lithium halogenides was examined in vitro. The experiments were conducted with cell lines of human (HeLa and K562) and murine (L5178Y) tumour cells. Dog Kidney Epithelial Cell Line MDCK was used as a control. The anti-tumor function of AID was measured using IC50 measurements. The medication was administered at concentrations of 500 μg / ml, 250 μg / ml, 125 μg / ml, 63 μg / ml, 32 μg / ml, 16 μg / ml, 80 μg / ml and 8 μg / ml respectively. μg / ml; 4 μg / ml; 2 μg / ml; 1 μg / ml; and 0.5 μg / ml , respectively. For Hela, K562, L5178Y and MDCK cells, the IC50s were found to be 112 μg / ml, 11.8 μg / ml, 10.3 μg / ml and 40.6 μg / ml respectively. The findings of the molecular modelling method and DFT calculations illustrate the possible mechanism of the cytotoxic activity of the drug. Help interacts with onco-DNA, and the following inhibitory complexes are formed: Help-included lithium (Li) halogenide forms a complex with the phosphate group, while adenosine or guanosine nitrogenous bases and Li halogenide organise the molecular iodine. The interaction of the topo I active site with the phosphate group is disrupted by these inhibitory centres, and two new nucleoprotein complexes are formed. In one, the residue of Arg amino acid is bound with the phosphate group by the Li halogenide complex, and in the second, Tyr is bound with the molecular iodine and Li halogenide adenosine complex. The possibility of using AID as an antitumor drug against certain cancer cells , specifically against leukaemia, has been shown by experimental research. Calculations have shown that the action of Help on onco-DNA results in the creation of the following inhibitory complexes: the lithium-phosphate group complex of halogens (structure Ia, b) and the complexes in which adenosine or guanosine and lithium halogenide nitrogen bases are coordinated by molecular iodine (structure IIa, b-IIIa, b).


Author (s) Details

G. A. Yuldasheva
Scientific Centre for Anti-Infectious Drugs, Kazakhstan, Russia.

G. M. Zhidomirov
Boreskov Institute of Catalysis SB RAS, Russia.

A. O. Abekova
Scientific Centre for Anti-Infectious Drugs, Kazakhstan, Russia.

Ilin AI
Scientific Centre for Anti-Infectious Drugs, Kazakhstan, Russia.

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