Totarol是一种非特异性细菌细胞分裂蛋白FtsZ的抑制剂。
Cas No.:511-15-9
Sample solution is provided at 25 µL, 10mM.
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Totarol is a non-specific inhibitor of the bacterial cell division protein FtsZ[1]. Totarol directly targets and binds to the FtsZ protein, inhibiting its assembly into the Z-ring, thereby blocking bacterial cell division and proliferation. Totarol is commonly used in research on novel antibacterial drugs, particularly against drug-resistant Gram-positive bacteria (such as Staphylococcus aureus) and Mycobacterium tuberculosis[2]. Totarol can also inhibit Fe(III)-ADP/NADPH-induced lipid peroxidation in rat liver microsomes and mitochondria, as well as the auto-oxidation of linoleic acid[3].
In SGC-7901 human gastric cancer cells and GES-1 cells, Totarol (0-400μM;24h) exhibited dose-dependent cytotoxicity in SGC-7901 cells, while GES-1 cells were less affected. This indicates that tocotrienol targets cancer cells and has less toxicity to normal cells (GES-1) [4]. In the hemolysis assay, Totarol（0.25-1μg/ml；30min） significantly inhibited the hemolytic effect when incubated with rabbit red blood cells at 37℃ for 30 minutes[5]. In RAW264.7 macrophages, when Totarol (0.25-1μg/ml; 16h) was co-cultured with Staphylococcus aureus culture supernatant, the release of TNF-α was reduced[6].
Totarol(0.1-10μg/kg; ip; 2-6h) reduced infarct volume and improved the neurological deficit after acute focal cerebral ischemia[7].
References:
[1]. Kelley C. Design and synthesis of novel FtsZ-targeting antibacterial agents[M]. Rutgers The State University of New Jersey, School of Graduate Studies, 2014.
[2]. Domadia P, Swarup S, Bhunia A, et al. Inhibition of bacterial cell division protein FtsZ by cinnamaldehyde[J]. Biochemical pharmacology, 2007, 74(6): 831-840.
[3]. Haraguchi H, Ishikawa H, Kubo I. Antioxidative action of diterpenoids from Podocarpus nagi[J]. Planta Medica, 1997, 63(03): 213-215.
[4]. Xu T, Huang L, Liu Z, et al. Totarol, a natural diterpenoid, induces selective antitumor activity in SGC-7901 human gastric carcinoma cells by triggering apoptosis, cell cycle disruption and suppression of cancer cell migration[J]. J. BUON., 2019, 24: 686-692.
[5]. Shi C, Zhao X, Li W, et al. Inhibitory effect of totarol on exotoxin proteins hemolysin and enterotoxins secreted by Staphylococcus aureus[J]. World Journal of Microbiology and Biotechnology, 2015, 31(10): 1565-1573.
[6]. Seca A M L, Pinto D, Silva A M S. The current status of bioactive metabolites from the genus Juniperus[J]. Bioactive phytochemicals: Perspectives for modern medicine, 2015, 3: 365-408.
[7]. Gao Y, Xu X, Chang S, et al. Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction[J]. Toxicology and applied pharmacology, 2015, 289(2): 142-154.
Totarol是一种非特异性细菌细胞分裂蛋白FtsZ的抑制剂[1]。Totarol可直接靶向并与FtsZ蛋白结合，抑制其组装成Z环，从而阻断细菌的分裂与增殖。该化合物通常用于新型抗菌药物的研究，特别是针对耐药性革兰氏阳性菌（如金黄色葡萄球菌）和结核分枝杆菌的研究[2]。此外，Totarol也能抑制Fe(III)-ADP/NADPH诱导的大鼠肝微粒体及线粒体脂质过氧化，以及亚油酸的自氧化[3]。
在人胃癌SGC-7901细胞和正常胃黏膜上皮GES-1细胞中，Totarol（0-400μM；24h）对SGC-7901细胞表现出剂量依赖性细胞毒性，而对GES-1细胞的影响较小，表明其对癌细胞具有靶向性，对正常细胞（GES-1）的毒性较低[4]。在溶血实验中，Totarol（0.25-1μg/ml；30min）与兔红细胞在37℃共孵育30分钟后，能显著抑制溶血作用[5]。在RAW264.7巨噬细胞中，当Totarol（0.25-1μg/ml；16h）与金黄色葡萄球菌培养上清液共培养时，能减少TNF-α的释放[6]。
Totarol（0.1-10μg/kg；ip；2-6h）能够减少大鼠急性局灶性脑缺血后的梗死体积，并改善神经功能缺损[7]。
| Antibacterial susceptibility testing[1]: | |
Preparation Method | The bacteria cultured at 37°C overnight with constant shaking were diluted with MH broth to adjust to a final concentration of 105 colony-forming units (CFU)/ml. Totarol was prepared in MH broth to aquire different subinhibitory concentrations (0.0625, 0.125, 0.25, 0.5, 1, 2, 4, 8, 16µg/ml) by serial microdilutions. Then a 50µl aliquot of Totarol dilutions of different subinhibitory concentrations and 50µl of the bacterial suspension were added into individual wells of a 96-well microtiter plate. Wells without Totarol treatment served as positive growth controls. Then the plates were incubated for 16 to 24h at 37°C. The MIC was defined as the lowest concentration of drug that inhibited>90% of the microorganism’s growth by optical density (OD) at 600nm using a microtiter plate reader. |
Reaction Conditions | 0.0625, 0.125, 0.25, 0.5, 1, 2, 4, 8, 16µg/ml；16-24h |
Applications | Totarol has an MIC value of 2μg/ml against Staphylococcus aureus ATCC 29213. |
| Cell experiment [2]: | |
Cell lines | Primary rat cerebellar granule cells (CGCs) |
Preparation Method | Excitotoxicity was induced by exposing cerebellar granule cells (CGCs) to 200μM glutamate for 24 hours, or by depriving them of the serum substitute B27 for 24 hours. To determine the neuroprotective effect of Totarol, cells were pretreated with different concentrations of Totarol for 24 hours. |
Reaction Conditions | 0.1-5μM; 24h |
Applications | Totarol prevents glutamate-, nutrient deprivation-, and OGD-induced neurotoxicity in CGCs in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Transient middle cerebral artery occlusion |
Preparation Method | Rats underwent transient middle cerebral artery occlusion (tMCAO) surgery. The right common carotid artery (CCA), internal carotid artery (ICA), and external carotid artery (ECA) of each rat were exposed. A single strand of nylon suture with a rounded tip (approximately 0.26mm in diameter) was inserted into the ICA through the ECA stump and gently advanced to the MCA. After 2 hours of MCAO, the suture was removed to restore blood flow (reperfusion). Body temperature was maintained at 37°C using a temperature control system. All animals had free access to food and water. Animals were randomly divided into six groups: sham group, vehicle group, Totarol (0.1μg/kg) group, Totarol (1μg/kg) group, Totarol (10μg/kg) group, and edaravone (3mg/kg) group. Edaravone was used as a positive control because of its therapeutic effect on ischemic stroke as a free radical scavenger. Totarol and edaravone were administered intravenously to the rats at 2, 4, and 6 hours after ischemia. |
Dosage form | 0.1-10μg/kg; ip; 2-6h |
Applications | Totarol reduced infarct volume and improved the neurological deficit after acute focal cerebral ischemia. |
References: | |
| Cas No. | 511-15-9 | SDF | |
| 别名 | 桃柁酚,NSC 299936, (+)-Totarol, trans-Totarol | ||
| 化学名 | (4bS,8aS)-4b,5,6,7,8,8a,9,10-octahydro-4b,8,8-trimethyl-1-(1-methylethyl)-2-phenanthrenol | ||
| Canonical SMILES | OC(C=C1)=C(C(C)C)C2=C1[C@]3(C)[C@](CC2)([H])C(C)(C)CCC3 | ||
| 分子式 | C20H30O | 分子量 | 286.5 |
| 溶解度 | 2mg/mL in ethanol, 10mg/mL in DMSO, 2.5mg/mL in DMF | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.4904 mL | 17.452 mL | 34.904 mL |
| 5 mM | 698.1 μL | 3.4904 mL | 6.9808 mL |
| 10 mM | 349 μL | 1.7452 mL | 3.4904 mL |
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