Enzyme Inhibitors

Clavulanic acid, lithium salt or lithium clavulanate is an irreversible inhibitor of β-lactamase class A enzymes, which target β-lactam antibiotics. Clavulanic acid, lithium salt has been shown operate more efficiently with ceftazidime and amoxicillin antibiotics. Research has also shown an increase in AmpC β-lactamase expression when lithium clavulanate was administered in vitro to Enterobacteriaceae.

Clavulanic acid, lithium salt potentiates antibiotic effects of penicillin binding protein (PBP) inhibitors by preventing their deconstruction. Effective inhibition of β-lactamases by this compound expand antibiotic duration and lethality, making it useful for susceptibility tests or bacterial selection.

Clofazimine is an active phenazine composed of an imino group and aromatic tricyclic heterocycles that is used as an antimycobacterial, anti-inflammatory and anti-cancer compound. It has been shown to be a potent in vivo antimycobacterial agent toward Mycobacterium leprae and in vitro to Mycobacterium avium.

As an anti-inflammatory, clofazimine inhibits reactive oxygen species (ROS) formation within neutrophils by inhibiting myeloperoxidase catalyzed reactions. The formed ROS are responsible for activating tumor necrosis factor alpha (TNFα) and interleukin 8 (IL8), which are inflammatory cytokines.

Cloxacillin sodium is a sodium salt formed from a chlorinated semisynthetic derivative of penicillin. It has been shown to exhibit significant bactericidal activity against penicillin G-resistant staphylococci.

Penicillins are a type of β-lactam antibiotic consisting of a four-membered β-lactam ring bound to a five-membered thiazolidine ring. This two-ring system causes distortion of the β-lactam amide bond, resulting in decreased resonance stabilization and increased reactivity. β-lactams inhibit the formation of peptidoglycan cross-links within bacterial cell walls by targeting penicillin-binding proteins or PBPs. Consequently, the bacterial cell wall becomes weak and cytolysis occurs. Resistance to β-lactam antibiotics occurs in the presence of cells containing plasmid encoded extended spectrum β-lactamases or ESBLs.

Antibiotics are often used in clinical in vitro tests known as antimicrobial susceptibility tests or ASTs to determine their efficacy against certain bacterial species. They are tested against gram-negative and gram-positive bacteria using panels, discs, and MIC strips by medical microbiologists. ASTs decrease the risk of using an antibiotic against bacteria exhibiting resistance to it, and the results are used in clinical settings to determine which antibiotic(s) to prescribe for various infections.

Cysteamine Hydrochloride or cysteamine is a mercaptoethylamine hydrochloride salt reductant that forms in mammals from pantetheine formation by degrading Coenzyme A. It has been used as a cystine depleting agent as well as a somatostatin inhibitor.

Cysteamine has been shown in vivo to remove accumulated cystine in lysosomes by forming disulfide bridges with cystine. The interaction between cysteamine and cystine forms cysteine and cysteine-cysteamine mixed disulfide which can freely exit lysosomes.

Cysteamine has also been shown to inhibit somatostatin however, the mechanism of action has not been elucidated. It is believed to either inhibit somatostatin precursor formation or by promoting somatostatin degradation.

Dabrafenib is a compound used as a serine/threonine-protein kinase B-Raf inhibitor for oncology research. It competitively inhibits V600E BRAF gene mutations which are characteristic in melanoma cancers. Inhibition of B-Raf proteins, by dabrafenib, interrupts mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) pathways, which regulate cell growth.This action halts cell proliferative activity and engages apoptosis.

Dequalinium chloride is a quinolinium ion composed of symmetrical quaternary quinolinium units, one 4-amino-2-methylquinolin-1-yl group on each end of the molecule in place of a methyl hydrogen. It is a quaternary ammonium cation and forms an organic chloride salt. Its biological roles include antifungal agent and inhibitor of mitochondrial NADH ubiquione reductase. Medically, dequalinium chloride is the active ingredient of pharmaceuticals against bacterial infections and malaria; it has been applied as an antifungal, antinematadol and antiseptic drug.

Diethylpyrocarbonate (DEPC) is a moisture sensitive product that will readily decompose to ethanol and carbon dioxide in aqueous solution. DEPC can inhibit ryanodine binding to the ryanodine/Ca2+ receptor channel in a dose-and time-dependent manner, or work as a nuclease inhibitor. DEPC is often used to treat water used in the handling of RNA to remove RNases and reduce the risk of the RNA being degraded.

E-64 (trans-Epoxysuccinyl-L-leucylamido(4-guanidino)butane) irreversibly inhibits cysteine proteases without affecting other enzymes that contain cysteine residues. E-64 is capable of inhibiting bromelain, trypsin, papain, staphopain, calpain, collagenase, ficain, cathepsin B, H and L. Inhibition of serine proteases is not seen with E-64, excepting trypsin.

E-64 is usually used in a concentration range of 1 to 10μM. It is widely used for in vivo studies due to its cell permeability, low toxicity, and potency. E-64 is being investigated for the treatment of diseases caused by cysteine protease activity. It has been observed to inhibit programmed cell death and restore antigen and mitogen activity related to normal proliferative responses in T cells obtained from HIV+ donors.

Embelin is a benzoquinone derivative found in Ardisia japonica which is a plant native to eastern Asia. It is used as an anti-cancer compound as well as an anti-inflammatory. Embelin has also been exhibited anthelminthic properties against cestode parasites.

In oncology research, embelin has been used to disrupt X-linked inhibitor of apoptosis (XIAP) activity. Embelin binds the Baculovirus IAP Repeat 3 (BIR3) domain on XIAP and subsequently disrupts apoptosis regulation. Inactivation of BIR3 allows proteins caspase-9 and Diablo homologs/Smac proteins to freely promote apoptotic pathways.

Embelin has also been used to quell inflammatory responses by inhibiting eicosanoid synthesis.It has been shown that embelin targets eicosanoid synthesizing proteins 5-lipoxygenase (5-LO) and microsomal prostaglandin E2 synthase (MPGES). Embelin has also been shown to disrupt eicosanoid synthesis through XIAP suppression.

Emodin is a compound used as an anti-inflammatory and anti-cancer agent. It has been shown that emodin suppresses inflammatory responses in vitro by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) protein complexes. This effect occurs from emodin binding and preserving an inhibitory subunit on NF-κB.

Emodin has also been shown to induce apoptosis in mouse neuroectodermal tumors both in vivo and in vitro. Cell death is induced by inhibiting protein tyrosine kinase (PTK), a regulator of cell growth. Constraining PTK activity prevents further cell development which signals an apoptotic cascade.

EGCG has been shown to have a broad spectrum of antibacterial activity against gram positive and some gram negative bacteria. It is used synergistically with penicillin binding protein inhibitors because both target peptidoglycan on the cell wall. While the exact mechanism is not known, research on EGCG activity indicates bacterial cell wall damage by direct peptidoglycan binding.

Fipronil is a phenylpyrazole derivative that is used as an insecticide in agriculture for its neurotoxic effects. It is researched for environmental impact on aquatic and non-pest insect communities. Fipronil has been shown to have neurotoxic effects by inhibiting γ-aminobutyric acid (GABA) receptors on chloride channels. Inhibition of these channels hyperstimulates neurons and results with insect death. It has also been shown that fipronil has a high affinity for invertebrate GABA receptors and low affinity for vertebrate receptors.

Flubendazole is a benzimidazole compound that is used as an antiparasitic and anti-cancer agent. It has been shown to be an effective anthelminthic chemical by inhibiting tubulin synthesis and disrupting cytoskeleton formation. Flubendazole has also been shown in vivo to be a strong anti-cancer compound by the same mechanism and is potent toward vinblastine resistant cell lines.

Tubulin is vital protein component that provides the structural shape of cells as well as being integral to replication. Halting tubulin formation ruins the structural integrity and dysregulates cytosolic equilibrium. Tubulin inhibition also effects the subfamilies α-tubulin and β-tubulin which facilitate chromosomal migration during cellular replication.

Flumethasone is a glucocorticoid used as an anti-inflammatory for a variety of animals. It is commonly investigated for its effectiveness in animals to combat inflammatory symptoms caused by pathogens and to better understand inflammatory mechanisms. It is also used as to investigate novel techniques that detect and quantify steroid compounds within muscles.

Flumethasone has been shown to exert anti-inflammtory effects by functioning as a glucocorticoid receptor agonist. Stimulating this receptor promotes inhibition of phospholipase A2 activity. This enzyme catalyzes arachidonic acid into eicosanoids most of which stimulate anti-inflammation mechanisms.

Flurbiprofen is a phenylalkanoic acid that is part of the non-steroid anti-inflammatory family. It is used as a cyclooxygenase (COX) inhibitor, diminishing metabolites that activate inflammatory responses.

Flurbiprofen strongly inhibits two forms of the human COX enzyme: COX-1 and COX-2. Both enzymes catalyze the reaction of prostaglandin synthesis from arachidonic acid. COX-1 however has been found to influence other physiological processes such as mucus and acid secretion in the stomach.

Flurbiprofen sodium is the salt form of a phenylalkanoic acid that is part of the non-steroid anti-inflammatory drug (NSAID) family. It functions as a cyclooxygenase (COX) inhibitor and as an antimiotic. Flurbiprofen sodium has also been used to investigate in vivo novel drug delivery systems.

Flurbiprofen sodium strongly inhibits two forms of the human COX enzyme: COX-1 and COX-2. Both enzymes catalyze the synthesis of prostaglandin, a pro-inflammatory lipid, from arachidonic acid. COX-1 however has been found to influence other physiological processes such as mucus and acid secretion in the stomach. Antimiotic effects observed with flurbiprofen sodium use is due to decreased prostaglandin levels.

Fusidic acid is a fusidane antibiotic compound that exerts potent bacteriostatic effects toward gram positive bacteria. It is commonly implemented with bactericidal antibiotics such as rifampicin. Fusidic acid is an inhibitor of protein synthesis by disrupting amino acid transfer from tRNA to ribosomes.

Fusidic acid inhibits a GTPase called elongation factor G or translocase. Impeding translocase activity hidners movement of tRNA and mRNA through ribosomes. While predominant effects are bacteriostatic, higher concentrations will result in bacterial death.

Hydrocortisone is a glucocorticoid primarily produced by the adrenal cortex. It is used as an anti-inflammatory and is researched for its immunosuppressive and for glucose metabolism regulation. Hydrocortisone completes its action on a wide scale by binding glucocorticoid receptors which upregulates anti-inflammatory protein synthesis.

Hydroxyurea is a compound used in anti-cancer research to inhibit DNA synthesis and in sickle cell research for ways to alleviate symptoms. It has been shown to be a potent inhibitor of ribonucleotide reductase which reduces ribonucleotides to deoxyribonucleotides.

In vivo research has shown hydroxyurea converting into a free radical nitric oxide which binds the active site of ribonucleotide reductase, ceasing further DNA synthesis. The mechanism of nitric oxide release from hydroxyurea is not well understood.

Hydroxyurea has also been shown to alleviate sickle cell anemia through its conversion to nitric oxide in vivo. Nitric oxide alleviates endogenous nitric oxide loss, caused by hemolysis, and stimulates soluble guanylate cyclase (sGC) activity which will signal fetal hemoglobin production.

Imazapyr is imidazolinone family herbicide that has been used to research herbicidal resistances and biochemical pathways in an array of plants. This compound has been shown to uncompetitively inhibit acetolactate synthase (ALS) which catalyzes the production of the amino acids valine, leucine and isoleucine. Loss of these specific amino acids depletes physiologically important proteins and enzymes, eventually resulting in cell death.