Action Mechanism of Molecular Iodine Complex with Bioorganic Ligands, Magnesium and Lithium Halogenides on Human Tuberculosis Strain With Multiple Drug Resistance

摘要

Findings of a research on antibacterial effects of a newly synthesized iodine-containing drug (FS-1) against both the drug susceptible strain Mycobacterium tuberculosis H37Rv and an isolate of M. tuberculosis MS-115 with a multiple drug resistance phenotype, were discussed. The obtained results of the microbiological studies confirmed a bactericidal activity of FS-1 against sensitive and multi-drug resistant strains of M. tuberculosis at the concentrations from 8.2 μg/mL to 2.7 μg/mL during the entire investigation period (42 h). Spectrophotometry has shown that FS-1 causes changes in the permeability of the cell membrane of mycobacteria. Also it penetrates through the cytoplasmic membrane and causes the lysis of the cells (spheroplasts) partially devoid of the cell wall. Antibacterial action mechanism was studied by using the technique of the molecular modeling. Particularly, the DFT/CAM-B3LYP density potential approach has shown that the active center of FS-1, which contains magnesium ion, destroys the active catalytic complex of the DNA-dependent RNA polymerase (RNAP) and can disrupt in this way the transcription of bacterial RNA. Active center of FS-1 becomes a center of new nucleoprotein complex, which binds both the bacterial DNA and the ion Mg2+(COO-)3 within the catalytic RNAP complex. The conditions responsible for vital processes in the bacterial cell are violated. As a result, a cell lysis is observed.