Background: The thiazolide nitazoxanide (NTZ) is a broad-spectrum antiinfective
drug that adversely affects viability, growth, and proliferation of a range of
extracellular and intracellular protozoan, helminths, anaerobic and microaerophilic
bacteria, and viruses.
Method: Current review compiled the potential chemotherapeutic efficacy of NTZ
against a variety of such disease-causing macro and/or micro-organisms as well as
neoplastic cells, using various search engines viz. Web of Science, Scopus and Pub-
Med up to February 2017.
Result: The most accepted anti-infective mechanism of NTZ involves impairment of
the energy metabolism in anaerobic pathogens by inhibition of the pyruvate: ferredoxin/
flavodoxin oxidoreductase (PFOR). In parasitic-protozoan NTZ also induces
lesions/voids in the cell membrane and depolarises the mitochondrial membrane
along with the inhibition of quinone oxidoreductase NQO1, nitroreductase-1 and
protein disulphide isomerase. NTZ also inhibits the glutathione-S-transferase (a major
detoxifying enzyme) and modulates a gene (avr-14 gene) encoding for the alphatype
subunit of glutamate-gated chloride ion channel present in the nematodes. Apart
from well recognized non-competitive inhibition of the PFOR in anaerobic bacteria,
NTZ also showed a variety of other antibacterial mechanisms viz. inhibits pyruvate
dehydrogenase in the Escherichia coli, disrupts the membrane potential and pH homeostasis
in the Mycobacterium tuberculosis, suppresses the chaperone/usher (CU)
pathway of the gram-negative bacteria and stimulates host macrophage autophagy in
the tubercular patients. NTZ also suppresses the viral replication by inhibiting maturation
of the viral hemagglutinin and the viral transcription factor immediate early 2
(IE2) as well as by activating the eukaryotic translation initiation factor 2α (an antiviral
intracellular protein). Additionally, NTZ expresses inhibitory effect on the tumour
cell progression by modulating drug detoxification (glutathione-S-transferase P1),
unfolded protein response, autophagy, anti-cytokines activities and c-Myc inhibition.
Conclusion: These potentially versatile molecular interactions of NTZ within invading
pathogen(s) and immunomodulatory efficacy over the hosts, justify the multifunctional
chemotherapeutic significance of this chemical agent.