isomerase

AY 9944 is a specific cholesterol biosynthesis inhibitor that targets the 7-dehydrocholesterol Δ7-reductase (DHCR7) enzyme (IC50=13 nM). At high doses, AY 9944 also inhibits sterol Δ7-Δ8 isomerase in cultured embryos, leading to the accumulation of cholest-8-en-3β-ol[1][2][3]. Additionally, AY 9944 causes hypocholesterolemia and accumulation of 7DHC.

Glucose 6-phosphate isomerase (GPI), also known as phosphoglucose isomerase phosphoglucoisomerase (PGI) or phosphohexose isomerase (PHI), is a highly conserved glycolytic and dimeric enzyme often used in biochemical studies that catalyzes the reversible isomerization of glucose-6-phosphate to fructose-6-phosphate [1].

Triosephosphate isomerase (TPI), a glycolytic enzyme, efficiently catalyzes the interconversion between dihydroxyacetone phosphate and D-glyceraldehyde-3-phosphate. The catalytic site of TPI is located at the dimer interface [1].

Phosphomannose isomerase, the initial enzyme in GDP-Man biosynthesis, catalytically facilitates the interconversion of fructose-6-phosphate (Fru6P) and mannose-6-phosphate (Man6P), playing a crucial role in cell wall synthesis and protein glycosylation. It is also recognized as a significant antifungal target against threats from A. flavus [1].

Topoisomerase II inhibitor 13 inhibits topoisomerase II (Topo II) that shows strong anti-proliferation activity against HL-60 MX2 cancer cells derived from HL-60 against Topo II toxicity.

Topoisomerase II inhibitor 14 is a potent topoisomerase II inhibitor with anticancer and antioxidant activities.Topoisomerase II inhibitor 14 induces apoptosis and blocks the cell cycle in S phase.Topoisomerase II inhibitor 14 reduces the amount of GSH, MDA and NO. Topoisomerase II inhibitor 14 reduces the amount of GSH, MDA and NO.

Topoisomerases ribosomes-IN-1 (compound 30f) serves as an inhibitor targeting both ribosomes and topoisomerases, specifically exhibiting inhibitory actions against constitutively macrolide-resistant bacteria. This compound effectively suppresses bacterial protein synthesis (IC 50 : 0.647 μM) and hampers DNA replication (IC 50 : 0.218 μM).

Topoisomerase inhibitor4 (compound 45) acts as an effective inhibitor of Topoisomerase1 2, arresting the cell cycle at the G2 M phase and inducing Apoptosis. This compound exhibits potent antitumor activity.

TopoisomeraseI II inhibitor 5 (compound 1) stabilizes G4 structures through binding and concurrently inhibits the relaxation activities of TopoI and II.

TopoisomeraseI II inhibitor 6 (compound 3i) acts as an effective inhibitor of topoisomerase I and II, with IC50 values of 4.77 µM and 15 µM, respectively. Additionally, it exhibits antiproliferative activity against the human melanoma cell line LOX IMVI, demonstrating IC50 values of 26.7 µM and 25.4 µM.

TopoisomeraseII Inhibitor 20 TFA is a potent inhibitor of topoisomerase II with an IC50 of 0.98 µM. It can induce cell apoptosis and exhibits broad-spectrum anticancer activity.

TopoisomeraseI inhibitor 17 (Compound 7h) is an inhibitor of TopoisomeraseI (Top1). It reduces DDX5 and reverses the locking effect of DDX5 on Top1 activity. This compound induces Top1-mediated DNA damage and promotes reactive oxygen species (ROS) production. It triggers apoptosis by decreasing anti-apoptotic proteins XIAP, Bcl-2, and Survivin, while increasing pro-apoptotic proteins Bax and γH2AX. Moreover, TopoisomeraseI inhibitor 17 halts progression at the G2 M checkpoint, leading to cell cycle arrest. It significantly impairs colorectal cancer cell colony formation and migration, and effectively reduces tumor size in human PDX tumor mouse models.

Topoisomerase inhibitor 5 (compound 158) is an inhibitor of bacterial topoisomerase, with a minimum inhibitory concentration of 0.125 μg mL, and exhibits anti-tuberculosis activity.

Compound 5h (Topoisomerase I II inhibitor 7) is a Topoisomerase I II inhibitor.

TopoisomeraseIIα-IN-10 (Compound 13r) is a topoisomerase IIα inhibitor that binds to the active site of DNA when complexed with topoisomerase IIα. This binding is stabilized through interactions with DNA base pairs and amino acid residues. By intercalating into DNA, TopoisomeraseIIα-IN-10 induces apoptosis and disrupts the mitochondrial membrane potential in HCT116 cells, effectively inhibiting their growth with an IC50 of 4.37 μM. It is applicable for cancer research studies.

TopoisomeraseI II inhibitor 8 (Compound Ru7) is a dual catalytic inhibitor of TopoisomeraseI II that induces DNA damage and activates PARP-1, leading to the activation of RIPK1, RIPK3, and MLKL, ultimately causing necroptosis. It shows significant anticancer activity by effectively targeting cancer cell nuclei and inducing cell death through necroptosis, offering substantial clinical potential in overcoming resistance in cancer treatment.

Topoisomerase I inhibitor 2 (ZML-8) is a highly selective DNA topoisomerase I (Top1) inhibitor that impedes Top1 activity, causing DNA damage. It arrests the cell cycle at the G2 M phase and induces apoptosis, exhibiting anti-tumor effects [1].

Topoisomerase I (Compound ZML-14) inhibitor 3 induces HepG2 cell apoptosis and arrests cell cycle at G2 M phase. Topoisomerase I inhibitor 3 is an inhibitor of topoisomerase I that interact with topoisomerase I-DNA complex [1].

Topoisomerase II inhibitor 8 (compound 22) is a potent inhibitor of topoisomerase II (IC50 = 0.52 μM) [1] and exhibits strong anti-proliferative activities, arresting the cell cycle at the G2 M phase.

Topoisomerase II inhibitor 6 (Compound 5), a tryptanthrin derivative, is a potent and selective topoisomerase II inhibitor that blocks the CCRF-CEM cell cycle in the G2 phase and induces DNA double-strand breaks (DSB). It exhibits antiproliferative activity on various tumor cell lines and has potential for cancer research [1].

Topoisomerase I II inhibitor 2 (compound 1a) is a DNA topoisomerase I II dual inhibitor that significantly reduces xenograft tumor growth in a mouse model, indicating its potential use in treating liver cancer. It is a potent topoisomerase inhibitor with IC50 values of 6.83 μM and 9.82 μM for LM9 cells and Huh7 cells [1].

Type II topoisomerase inhibitor 1 is a potent and selective inhibitor of E. coli DNA gyrase with an IC50 value of 1.7 nM and forms hydrogen bonds with the Asp73 residue. It inhibits topoisomerase IV activity with an IC50 value of 0.98 μM and is applicable in the antibacterial area [1] [2].

Topoisomerase II inhibitor 3 (Compound 6 h) is an acridone derivative acting as a Type II DNA topoisomerase (topo II) inhibitor. It specifically targets topo IIα β subtypes, with IC50 values of 0.17 μM for topo IIα and 0.23 μM for topo IIβ, causing significant DNA damage and inducing apoptosis by triggering the loss of mitochondrial membrane potential [1].

Topoisomerase IIα-IN-4 (F2) is a non-intercalative ATP-competitive inhibitor of human DNA topoisomerase II, selectively inhibiting TopoIIα with an IC50 value of 3.8 μM and TopoIIβ with an IC50 value of 10.1 μM. It induces apoptosis and arrests the cell cycle in HepG2 cells, demonstrating strong antitumor effects against various human cancer cell lines, thereby highlighting its significance for cancer research [1].