complex iii

Complex III-IN-2 (Compd 4d-2) is a complex III inhibitor with antifungal activity, exhibiting EC50 values of 29.31 mg L against R. solani and 29.98 mg L against Sclerotinia sclerotiorum [1].

Complex III-IN-1 (Compd 4c-2) is an inhibitor of complex III with antifungal activity, exhibiting an EC50 value of 18.53 mg L against Sclerotinia sclerotiorum [1].

Naroparcil, an orally available thioglycoside analog of 4-methylumbelliferyl β-D-xyloside, showed antithrombotic effects in the Wessler sludge model of venous thrombosis (jugular vein).Naroparcil enhanced the formation of the thrombin heparin cofactor II complex, induced dermatophyte sulfate-like substances in plasma from treated rabbits appearance, but reduced the formation of thrombin antithrombin III complexes in plasma incubated with (125I)-human alpha-thrombin.

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

CYP3A4-IN-4 (compound Δ,Λ-3) constitutes a Ru(II)-Ir(III) complex that acts as a photoactive inhibitor of the primary human drug-metabolizing enzyme CYP3A4. This complex features a [Ru(tpy)(Me2bpy)] photocaging group and exhibits an IC50 of 2.2 μM for the inhibition of microsomal CYP3A4 under irradiation conditions (λirr=530 nm, tirr=15 min). The phototherapeutic index (PI) of CYP3A4-IN-4 is 5.4.

c(avb6)-DOTA TFA is a conjugate formed by the coupling of a selective αvβ6 integrin cyclic peptide and a DPTA chelating agent. The Lu (III) complex of c(avb6)-DOTA TFA exhibits considerable affinity for αvβ6 integrin (IC50=0.8 nM), making it suitable for tumor diagnostics.

BGC4 is a gold(III) complex based on biphenyl. It inhibits human recombinant thioredoxin reductase (TrxR) with an IC50 of 10.7 μM, exhibits cytotoxicity with an IC50 of 5.4 μM in MDA-MB-231 cells, and induces apoptosis. Additionally, BGC4 demonstrates antitumor activity in mouse models.

S3QEL-2 is a selective complex III superoxide-producing site inhibitor with neuroprotective effects that inhibits PC-3 cell proliferation in pyruvate-starved medium in a dose-dependent manner.

GSK 932121 is a potent antimalarial agent. GSK 932121 inhibits selectively the electron-transport chain in P. falciparum at the cytochrome bc1 level (complex III).

Collismycin A is a bacterial metabolite from *Streptomyces* with antibacterial, antiproliferative, and neuroprotective properties. It exhibits activity against various bacteria (MICs = 6.25-100 μg ml) and fungi (MICs = 12.5-100 μg ml). It inhibits proliferation of A549 lung, HCT116 colon, and HeLa cervical cancer cells (IC50s = 0.3, 0.6, and 0.3 μM, respectively) and NIH373 fibroblasts (IC50 = 56.6 μM) but not MDA-MD-231 breast cancer cells (IC50 > 100 μM). Collismycin A forms a complex with Fe(II) and Fe(III) in a 2:1 ratio, with iron ions inhibiting its antiproliferative effect on HeLa cells, an effect not observed with zinc, manganese, copper, or magnesium ions. Additionally, Collismycin A (1 μM) reduces apoptosis in zebrafish larvae brain regions by 44% in a model of neuronal cell death induced by all-trans retinoic acid.

Antimycin A4 is an active component of the antimycin A antibiotic complex that is more polar than antimycin A1 , antimycin A2 , and antimycin A3 . Antimycin A4 inhibits ATP-citrate lyase with a Ki value of 64.8 μM. The antimycin A complex is a mixture of antimycins A1, A2, A3, and A4 that demonstrates antifungal, insecticidal, nematocidal, and piscicidal properties. It blocks mitochondrial respiration and can deplete cellular levels of ATP via inhibition of complex III of the mitochondrial electron transport chain (ETC). Antimycin A prevents the transfer of electrons between the b-cytochromes and ubiquinone at the Q(inner) site of complex III. This results in the stabilization of the ubisemiquinone radical at the Q(outer) site of complex III, leading to increased production of superoxide. Antimycin A is widely used in research to shunt electron flow through the ETC to study the chemical details of oxygen respiration. Additionally, antimycin A has been shown to inhibit Bcl-2 and Bcl-xL proteins, inducing apoptosis.

Chlorido[N,N'-disalicylidene-1,2-phenylenediamine]iron(III) is an inducer of ferroptosis.1 It induces ferroptosis, but not apoptosis or necroptosis, in NB1 cancer cells when used at a concentration of 3 μM.1 Chlorido[N,N'-disalicylidene-1,2-phenylenediamine]iron(III) inhibits proliferation of BJAB, NALM-6, Jurkat, MelHO, and MCF-7 cancer cells (IC50s = 0.07, 2.5, 1.5, 3, and 5 μM, respectively), as well as NALM-6 cells resistant to daunorubicin and vincristine when used at concentrations ranging from 0.04 to 0.125 μM.2 |1. Sagasser, J., Ma, B., Baecker, D., et al. A new approach in cancer treatment: Discovery of chlorido[N,N'-disalicylidene-1,2-phenylenediamine]iron(III) complexes as ferroptosis inducers. J. Med. Chem. 62(17), 8053-8061 (2019).|2. Lee, S.-Y., Hille, A., Kitanovic, I., et al. [FeIII(salophene)Cl], a potent iron salophene complex overcomes multiple drug resistance in lymphoma and leukemia cells. Leuk. Res. 35(3), 387-393 (2011).

MnTBAP chloride (Mn(III)TBAP) is a cell-permeable superoxide dismutase (SOD) mimetic and peroxynitrite scavenger that reduces the doubling time of SOD-E. coli by a factor of 2. MnTBAP chloride exhibits anti-inflammatory effects through upregulation of BMPR-II and inhibition of NFκB signaling. mnTBAP chloride is a manganese porphyrin complex with antioxidant properties and has potential for use in the study of fibrotic responses in chronic kidney diseases (CKDs).

Metyltetraprole is a potent fungicide that demonstrates promising efficacy against sensitive wild-type and G143A mutant strains of Zymoseptoria tritici, as indicated by its low EC50 values of 0.002 ppm. Additionally, this compound exhibits effectiveness against QoI-resistant strains. Metyltetraprole functions by inhibiting the respiratory chain through complex III [1] [2].

Ametoctradin is an inhibitor of the Qo site of mitochondrial respiratory complex III. It is an agricultural fungicide that selectively inhibits the cytochrome bc(1) complex of Onychomycetes, and can be used for the study of Onychomycetes diseases.

NecroIr1, an iridium(III) complex, acts as a necroptosis inducer in Cisplatin-resistant lung cancer cells (A549R). It selectively targets mitochondria, causing oxidative stress and reducing mitochondrial membrane potential (MMP). By activating receptor-interacting serine-threonine kinase 3 (RIPK3) and Mixed Lineage Kinase (MLKL), and modulating CDK4 expression, NecroIr1 facilitates cell death mechanisms [1].

NecroIr2, an iridium(III) complex, functions as a necroptosis inducer in cisplatin-resistant lung cancer cells (A549R). It preferentially accumulates in mitochondria, causing oxidative stress and a reduction in mitochondrial membrane potential (MMP). Moreover, NecroIr2 initiates the activation of receptor-interacting serine threonine kinase 3 (RIPK3) and mixed lineage kinase domain-like pseudokinase (MLKL), while also regulating CDK4 expression [1].

Caspase-3 activator 1 (compound 4b), a Ru(III) metal complex, effectively inhibits gastric tumor growth and metastasis by mediating caspase-3 cleavage, enabling Caspase-3 to process gasdermin E (GSDME), resulting in GSDME-N terminus production and perforation of the gastric tumor cell membrane. Furthermore, compound 4b induces pyroptosis and subsequent immune responses and can be incorporated with decitabine (DCT) into the 4b-DCT-Lip lipid delivery system [1].

HP661, a selective inhibitor of mitochondrial complex I (NADH dehydrogenase), impedes complex I activity by 77.6% at 1 µM, demonstrating lesser inhibition towards complex III (28.1%) and no inhibitory effects on complexes II and IV. It notably decreases the viability of human lung cancer cells—H460, NCI H441, and trametinib-resistant A549 cells (IC50s = 10.6, 29.7, and 15.1 nM, respectively)—which exhibit high levels of oxidative phosphorylation. In contrast, it shows minimal activity against NCI H358 lung cancer cells and non-cancerous HPNE and MRC-5 cells (IC50s = >10,000 nM for both), which have lower oxidative phosphorylation levels. Furthermore, in an H460 mouse xenograft model, HP661 at a dose of 30 mg/kg twice daily significantly reduces tumor volume and enhances the tumor-growth inhibitory effects of trametinib.

HQNO is a natural product isolated from P. aeruginosa,and is a potent inhibitor of electron transport chain(Kd of 64 nM for complex III). It also is a potent mitochondrial NDH-2 inhibitorin many species.

Heparin (Nadroparin) calcium (MW 3600-5000), an anticoagulant, forms a reversible complex with antithrombin III (ATIII), known as the heparin-antithrombin III complex. This complex then irreversibly binds to and inactivates thrombin and other activated clotting factors IX, X, XI, and XII, thereby inhibiting the conversion of fibrinogen to fibrin [1] [2].

Heparin calcium (MW 15000-19000), an anticoagulant, forms a reversible complex with antithrombin III (ATIII), known as the heparin-antithrombin III complex. This complex binds to thrombin and the activated clotting factors IX, X, XI, and XII, leading to their irreversible inactivation and inhibiting the conversion of fibrinogen into fibrin [1] [2].

TfR-1-IN-1 is a transferrin receptor 1 (TfR-1) inhibitor, also an Fe(III) salivary phenol complex, with anticancer activity. It induces apoptosis, inhibits the growth of tumor cells and normal cells, and is used in studies of leukemia.

Ertumaxomab (Anti-Human CD22 Recombinant Antibody) is a bispecific antibody that targets both HER2 neu and CD3. It functions by activating Fcγ type I III receptors, which facilitates the formation of a tri-cell complex involving tumor cells, T cells, and accessory cells. This compound has been utilized in the research of breast cancer [1].