Inosine 5′-Monophosphate Dehydrogenase Inhibitors as Antimicrobial Agents: Recent Progress and Future Perspectives

Shah, Chetan; Kharkar, Prashant S.

doi:10.4155/fmc.15.72

Cited by 31 publications

(26 citation statements)

References 53 publications

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“…Through its polyphenolic action, curcumin works competitively with an inhibitory role on the two isoforms of the enzyme inosine monophosphate dehydrogenase (IMPDH), which is a regulator of intracellular guanine nucleotides. It also plays a particularly important role in signal transduction, energy transfer, glycoprotein synthesis, DNA, RNA, and other multiple processes for cell vitality and proliferation [ 103 , 104 ].…”

Section: Curcumin and The Preventive Role In Hepatocellular Carcinmentioning

confidence: 99%

Curcumin and Photobiomodulation in Chronic Viral Hepatitis and Hepatocellular Carcinoma

Ailioaie

Litscher

2020

IJMS

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Immune modulation is a very modern medical field for targeting viral infections. In the race to develop the best immune modulator against viruses, curcumin, as a natural product, is inexpensive, without side effects, and can stimulate very well certain areas of the human immune system. As a bright yellow component of turmeric spice, curcumin has been the subject of thousands of scientific and clinical studies in recent decades to prove its powerful antioxidant properties and anticancer effects. Curcumin has been shown to influence inter- and intracellular signaling pathways, with direct effects on gene expression of the antioxidant proteins and those that regulate the immunity. Experimental studies have shown that curcumin modulates several enzyme systems, reduces nitrosative stress, increases the antioxidant capacity, and decreases the lipid peroxidation, protecting against fatty liver pathogenesis and fibrotic changes. Hepatitis B virus (HBV) affects millions of people worldwide, having sometimes a dramatic evolution to chronic aggressive infection, cirrhosis, and hepatocellular carcinoma. All up-to-date treatments are limited, there is still a gap in the scientific knowledge, and a sterilization cure may not yet be possible with the removal of both covalently closed circular DNA (cccDNA) and the embedded HBV DNA. With a maximum light absorption at 420 nm, the cytotoxicity of curcumin as photosensitizer could be expanded by the intravenous blue laser blood irradiation (IVBLBI) or photobiomodulation in patients with chronic hepatitis B infection, Hepatitis B e-antigen (HBeAg)-positive, noncirrhotic, but nonresponsive to classical therapy. Photobiomodulation increases DNA repair by the biosynthesis of complex molecules with antioxidant properties, the outset of repairing enzyme systems and new phospholipids for regenerating the cell membranes. UltraBioavailable Curcumin and blue laser photobiomodulation could suppress the virus and control better the disease by reducing inflammation/fibrosis and stopping the progression of chronic hepatitis, reversing fibrosis, and diminishing the progression of cirrhosis, and decreasing the incidence of hepatocellular carcinoma. Photodynamic therapy with blue light and curcumin opens new avenues for the effective prevention and cure of chronic liver infections and hepatocellular carcinoma. Blue laser light and UltraBioavailable Curcumin could be a new valuable alternative for medical applications in chronic B viral hepatitis and hepatocarcinoma, saving millions of lives.

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Section: Curcumin and The Preventive Role In Hepatocellular Carcinmentioning

confidence: 99%

Curcumin and Photobiomodulation in Chronic Viral Hepatitis and Hepatocellular Carcinoma

Ailioaie

Litscher

2020

IJMS

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“…If inhibited, the imbalance between the guanine and adenine nucleotide pools has dramatic consequences for cell proliferation 16 , rendering IMPDHs into a suitable cellular target of drugs widely used to date in chemotherapy as antivirals or as immunosuppressive and antitumor agents 17 . Due to the crucial role in de novo nucleotide biosynthesis and the significant clinical relevance, IMPDHs from various species are in the focus of investigations 18,19 .…”

mentioning

confidence: 99%

In cellulo crystallization of Trypanosoma brucei IMP dehydrogenase enables the identification of genuine co-factors

et al. 2020

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Sleeping sickness is a fatal disease caused by the protozoan parasite Trypanosoma brucei (Tb). Inosine-5'-monophosphate dehydrogenase (IMPDH) has been proposed as a potential drug target, since it maintains the balance between guanylate deoxynucleotide and ribonucleotide levels that is pivotal for the parasite. Here we report the structure of TbIMPDH at room temperature utilizing free-electron laser radiation on crystals grown in living insect cells. The 2.80 Å resolution structure reveals the presence of ATP and GMP at the canonical sites of the Bateman domains, the latter in a so far unknown coordination mode. Consistent with previously reported IMPDH complexes harboring guanosine nucleotides at the second canonical site, TbIMPDH forms a compact oligomer structure, supporting a nucleotidecontrolled conformational switch that allosterically modulates the catalytic activity. The oligomeric TbIMPDH structure we present here reveals the potential of in cellulo crystallization to identify genuine allosteric co-factors from a natural reservoir of specific compounds.

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“…Inosine-5'-monophosphate dehydrogenase (IMPDH) (spot 16) is an important enzyme to regulate the intracellular guanine nucleotide pool, which is essential for maintaining normal cell function and growth. As a purine biosynthetic enzyme IMPDH is essential for DNA and RNA synthesis, signal transduction, energy transfer, glycoprotein synthesis, and other cellular proliferation processes (Shah and Kharkar, 2015). Enolase (phosphopyruvate hydratase) (spot 19), which is overrepresented in Bti pHTppk, is a glycolytic enzyme involved in carbon metabolism.…”

Section: Energy Metabolismmentioning

confidence: 99%

Comparative proteomic analysis of Bacillus thuringiensis wild-type and two mutant strains disturbed in polyphosphate homeostasis

Yeşilırmak¹,

Doruk²,

Yilmaz³

et al. 2018

Turk J Biol

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IntroductionPolyphosphate (polyP), which is a linear polymer of phosphate (P i ) residues linked by high-energy phosphoanhydride bonds, is present in all organisms from bacteria to humans (Rao et al., 2009). PolyP has been shown to have important roles in a variety of cellular processes including regulation of enzyme activities, storage of P i and energy, adaptive responses to physical and chemical stresses, bacterial survival during the stationary phase, chelation of cations, maintenance of optimal translation efficiency, gene transcription control, and formation and function of cell membrane, channels, and pumps (Kornberg et al., 1999). PolyP has also been shown to be necessary for motility, biofilm formation, and other virulence properties of different bacteria such as Salmonella spp.

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Inosine 5′-Monophosphate Dehydrogenase Inhibitors as Antimicrobial Agents: Recent Progress and Future Perspectives

Cited by 31 publications

References 53 publications

Curcumin and Photobiomodulation in Chronic Viral Hepatitis and Hepatocellular Carcinoma

Curcumin and Photobiomodulation in Chronic Viral Hepatitis and Hepatocellular Carcinoma

In cellulo crystallization of Trypanosoma brucei IMP dehydrogenase enables the identification of genuine co-factors

Comparative proteomic analysis of Bacillus thuringiensis wild-type and two mutant strains disturbed in polyphosphate homeostasis

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