mitochondrial toxicity

Pyraclostrobin is one of the most heavily used fungicides that inhibits mitochondrial complex III of fungal and mammalian cells.

Polyphyllin D induces apoptosis via the mitochondrial apoptotic pathway as evidenced by decreased Bcl-2 expression levels, disruption of MMP and increased Bax, cytochrome C, and cleaved-caspase-3 levels. Polyphyllin D has an anti-angiogenic effect. Polyphyllin D has toxicity in human RBCs as well as its underlying mechanism for the hemolysis and eryptosis/erythroptosis. Polyphyllin D has strong anticancer activity, can overcome drug resistance in R-HepG2 cells and elicit programmed cell death via mitochondrial dysfunction.

Metacavir (PNA) is a novel nucleoside reverse transcriptase inhibitor, a deoxyguanosine analog, with anti-hepatitis B virus (HBV) activity and mitochondrial toxicity, which can be used to study HBV infection.

1. Oxyresveratro can inhibit tyrosinase activity. 2. Oxyresveratro is useful to trauma models, as toxicity to glia could be beneficial by inhibiting reactive gliosis. 3. Oxyresveratrol (trans-Oxyresveratrol) has antioxidant activity, can reduce neuronal oxidative damage and protect hepatocytes against oxidative stress and mitochondrial dysfunction, which may be associated with activation of Nrf2.

Pyrroloquinoline quinone (PQQ), as a well-known redox enzyme cofactor, PQQ can protect NS/PCs against glutamate toxicity associated with ROS-mediated mitochondrial pathway,

Quinine sulfate dihydrate plays a major role in potassium channel blockers. It is also used as an antimalarial, anticholinergic, antihypertensive and a hypoglycemic agent. It inhibits mitochondrial ATP-regulated potassium channel. It is also used to study the metabolism of biocrystalized heme, hemozoin, in malarial parasites and to study the toxicity of heme (FP)-complexes.

RLX (PD 139530) is a PI3K/Akt/FoxO3a signal inhibitor with anticancer activity against tumour cell lines such as colon cancer, inducing sub-G1 arrest and mitochondrial potential loss, thereby inhibiting tumour growth. RLX also exhibits antitussive and anti-asthmatic activity, reducing eosinophils and total lymphocytes in bronchoalveolar lavage (BAL) fluid, and exhibits toxicity toward A549 cells.

Biguanidinium-porphyrin free TFA is a mitochondrial-targeting photosensitiser exhibiting low dark toxicity towards human hepatocellular carcinoma HEp2 cells (IC50=8.2 mM, 1 J/cm²).

Aftin-4, an amyloid forty-two inducer, activates γ-secretase, promoting the generation of amyloid-β-1-42 (Aβ1-42) from amyloid-β protein precursor. Aftin-4(Aftin4) increased Aβ-1-42, but not Aβ-1-40 in mouse hipppocampus, accompanied by learning deficits and mitochondrial ultrastructural changes similar to those found in the brains of patients with AD. Aftin-4(Aftin4) can thus be used to induce a rapid, acute Alzheimer's disease-like toxicity in the rodent brain.

LDCA is a double-hit metabolic regulator that exhibits potent anti-proliferative activity. lDCA competitively inhibits LDH-A enzyme activity, alters mitochondrial hyperpolarization and simultaneously subverts apoptosis. lDCA has a pronounced effect in cancer cells and does not show toxicity.

Trifluralin (Treflan) is an agricultural herbicide with mild toxicity. Trifluralin is a novel pollutant that can interfere with mitochondrial respiration.

Apoptosisinducer 24 (Compound 4) inhibits the proliferation of gastric cancer cells with an IC50 range of 1.2-4.8 μM. It arrests the cell cycle at the G2/M phase, induces apoptosis in BGC-823 cells, and causes mitochondrial dysfunction. In mice, Apoptosisinducer 24 exhibits antitumor activity without significant toxicity, having an LD50 of 91.2 mg/kg.

Perfluorododecanoic acid (PFDoA) is a perfluoroalkyl substance (PFAS) identified in environmental samples such as lake trout tissue. Perfluorododecanoic acid reduces the viability of PC12 neuronal cells, elevates reactive oxygen species and malondialdehyde levels, and decreases mitochondrial membrane potential, collectively indicating its strong oxidative and mitochondrial toxicity, thereby highlighting its environmental and toxicological significance as a persistent organic pollutant.

IDOi-Pt(IV) prodrug-1 (Compound 10) is an IDOi-Pt(IV) prodrug that suppresses IDO expression. It induces apoptosis, reduces mitochondrial membrane potential, and inhibits tumor cell migration and invasion. Additionally, IDOi-Pt(IV) prodrug-1 triggers reactive oxygen species-mediated endoplasmic reticulum stress and the secretion of damage-associated molecular patterns (DAMPs), leading to immunogenic cell death (ICD). Compared to cisplatin, IDOi-Pt(IV) prodrug-1 exhibits relatively high efficiency and low toxicity in its antitumor activity.

IPH10 is an anticancer agent with strong antitumor effects in vivo and exhibits no liver or kidney toxicity. It significantly increases the reactive oxygen species (ROS) levels in tumor cells, decreases mitochondrial membrane potential, and induces apoptosis (apoptosis) in these cells.

Tubulin-IN-52 is a potent, selective tubulin polymerization inhibitor with an IC₅₀ of 2.9 μM. Tubulin-IN-52 induces apoptosis in tumor cells by triggering a caspase cascade via the mitochondrial apoptosis pathway. Tubulin-IN-52 significantly inhibits tumor growth without significant toxicity. Tubulin-IN-52 can be used in cancer-related research.

Tubulin inhibitor 50 (compound 07) is a microtubule protein inhibitor that enhances mitochondrial reactive oxygen species levels. It exhibits anticancer activity in HeLa cells with an IC50 value of 0.46 μM, while showing low toxicity in normal cell lines.

Mitochondrial-IN (C458) is a potent inhibitor of mitochondrial complex I. It offers significant protection against Aβ toxicity, exhibits favorable pharmacokinetic properties, and has minimal off-target effects.

COE-PNH2 exhibits antibacterial activity against Mycobacterium abscessus (Mab) with an MIC90 of 26 μM. It disrupts bacterial cell wall and membrane integrity, possesses intracellular permeability, and lacks mitochondrial toxicity.

NF-κB-IN-16 (compound 9) is a complex of an NF-κB inhibitor and Cisplatin (Pt(IV) complex) with potent and low-toxicity antitumor activity. It can cause DNA damage, induce mitochondrial dysfunction, generate reactive oxygen species, and trigger apoptosis via mitochondrial pathways and endoplasmic reticulum stress. NF-κB-IN-16 effectively inhibits the NF-κB/MAPK signaling pathway and disrupts PI3K/AKT signal transduction. Additionally, it demonstrates excellent in vivo antitumor efficacy and low toxicity in A549 or A549/CDDP xenograft models.

CX116 is an orally effective anti-inflammatory agent with significant anti-inflammatory properties. It exerts its effects by inhibiting inflammatory responses, reducing oxidative stress, protecting mitochondrial function, and preventing apoptosis (apoptosis). CX116 demonstrates acceptable toxicity and favorable pharmacokinetic characteristics, and it significantly safeguards mouse kidney tissue from Cisplatin-induced damage. CX116 is suitable for studying acute kidney injury caused by Cisplatin.

PARP1-IN-44 is a derivative of Olaparib and functions as an orally active PARP1 inhibitor with an IC50 of 0.6 nM. It also inhibits PARP2 (IC50 = 1.0 nM) and PARP7 (IC50 = 7.5 nM). PARP1-IN-44 demonstrates selective antiproliferative activity against BRCA-deficient cancer cells with minimal toxicity to normal cells. It induces G2/M phase arrest, promotes apoptosis, increases reactive oxygen species (ROS) levels, and disrupts mitochondrial membrane potential. Additionally, PARP1-IN-44 inhibits PARylation and leads to the accumulation of γH2AX. It activates the cGAS-STING pathway, enhancing the expression of IFN-β and CXCL10. In a CT26 tumor mouse model, PARP1-IN-44 enhances CD8+ T cell infiltration, showcasing significant in vivo antitumor activity.

FP802 is a potent oral TwinF interface inhibitor capable of disrupting and neutralizing the toxicity of the NMDAR/TRPM4 death complex. Within the 5xFAD Alzheimer's disease (AD) mouse model, FP802 demonstrates significant neuroprotective effects, preventing cognitive decline, preserving neuronal structural integrity, reducing β-amyloid plaque formation, and mitigating mitochondrial damage. In the amyotrophic lateral sclerosis (ALS) mouse model, FP802 prevents motor neuron loss, lowers serum neurofilament light chain (NfL) levels, improves motor performance, and extends the lifespan of mice. FP802 can be utilized for research related to Alzheimer's disease and amyotrophic lateral sclerosis [1][2].

PDK1-IN-5 is a selective inhibitor of PDK1 that reduces phosphorylation levels to activate PDH. This compound effectively reverses the Warburg effect by increasing acetyl-CoA, reducing lactate, elevating mitochondrial ROS, and subsequently inducing apoptosis, shifting cellular energy metabolism from glycolysis to oxidative phosphorylation. PDK1-IN-5 strongly inhibits tumor growth in vivo without causing systemic toxicity and can be used in research on lung adenocarcinoma, human non-small cell lung adenocarcinoma, gastric cancer, and colorectal cancer.