N. Hrynchuk (https://orcid.org/0000-0002-2069-5917),
N. Vrynchanu (https://orcid.org/0000-0003-3450-2108)
SI «Institute of Pharmacology and Toxicology of the National Academy of Medical Sciences of Ukraine», Kyiv
ANTIBACTERIAL PROPERTIES OF THIORIDAZINE
Key words: thioridazine, thioridazine derivatives, antibacterial action, microorganisms
A B S T R A C T
The emergence and spread of antibiotic-resistant strains of microorganisms reduces the effectiveness
of antibiotic therapy and requires finding solutions to problems, one of which is the study of antimicrobial
properties in drugs of various pharmacological groups.
The purpose of the work was to summarize the data on the antibacterial activity of thioridazine and its
derivatives to determine the feasibility and prospects of creating new antibacterial drugs on their basis.
The paper presents literature data on the effects of thioridazine on the causative agent of tuberculosis,
antistaphylococcal activity, susceptibility of plasmodium and trypanosoma.
The antibacterial activity of the drug was established within in vitro studies with the determination of MIC
towards gram-positive and gram-negative microorganisms, ex vivo using macrophage lines, as well as within
in vivo experiments on mice.
It is established that the neuroleptic thioridazine is characterized by pronounced anti-tuberculosis activity,
the mechanism of action is associated with the impact on the cell membrane of M. tuberculosis, inactivation by
calmodulin and inhibition of specific NADH-dehydrogenase type II.
The literature data indicate that thioridazine is able to increase the activity of isoniazid against the strains
of mycobacteria that are susceptible and resistant to its action. It has been established that resistance to
thioridazine in antibiotic-resistant M. tuberculosis strains is not formed.
The drug is characterized by its ability to inhibit the growth and reproduction of both methicylin-sensitive
(MSSA) and methicilin-resistant (MRSA) strains of Staphylococcus aureus, which has been proven within in
vitro experiments.
The effectiveness of thioridazine has been proven within in vivo experiments in case of skin infection
and sepsis caused by S. aureus. Antimicrobial effect of the drug is also observed towards to plasmodium
(P. falciparum) and trypanosomes (Trypanosoma spp.).
Currently, the synthesis of thioridazine derivatives is carried out to identify compounds with a pronounced
antibacterial effect. Some of the first synthesized compounds are not inferior or superior to thioridazine by the
inhibitory effect.
Thus, these data suggest that drugs of different pharmacological groups, including drugs that affect
the nervous system − thioridazine and its derivatives, can be a source of replenishment of the arsenal of
antimicrobial drugs to control such threatening infections as tuberculosis and diseases caused by polyresistant
strains of microorganisms.