Cycleanine
(Synonyms: 轮环藤碱) 目录号 : GC63967
An alkaloid with anticancer and antimalarial activities
Cas No.:518-94-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.00%
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Cycleanine is an alkaloid that has been found in T. subcordata and has anticancer and antimalarial activities.1,2 It selectively inhibits the growth of OVCAR-8, A2780, IGROV-1, and OVCAR-4 ovarian cancer cells (IC50s = 10, 7.6, 14, and 7.2 ?M, respectively) over non-cancerous ovarian surface epithelial cells (IC50 = 35 ?M).1 It also halts the cell cycle at the subG1 phase and induces apoptosis in OVCAR-8 cells. Cycleanine (25 and 50 mg/kg) reduces parasitemia and increases survival in a mouse model of infection with a chloroquine-resistant strain of P. berghei.2
1.Uche, F.I., Drijfhout, F.P., McCullagh, J., et al.Cytotoxicity effects and apoptosis induction by bisbenzylisoquinoline alkaloids from Triclisia subcordataPhytother. Res.30(9)1533-1539(2016) 2.Uche, F.I., Guo, X., Okokon, J., et al.In vivo efficacy and metabolism of the antimalarial cycleanine and improved in vitro antiplasmodial activity of semisynthetic analoguesAntimicrob. Agents Chemother.65(2)e01995-01920(2021)
| Cas No. | 518-94-5 | SDF | Download SDF |
| 别名 | 轮环藤碱 | ||
| 分子式 | C38H42N2O6 | 分子量 | 622.75 |
| 溶解度 | 储存条件 | 4°C, away from moisture and light | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.6058 mL | 8.0289 mL | 16.0578 mL |
| 5 mM | 0.3212 mL | 1.6058 mL | 3.2116 mL |
| 10 mM | 0.1606 mL | 0.8029 mL | 1.6058 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
The impact of Cycleanine in cancer research: a computational study
J Mol Model 2022 Oct 4;28(11):340.PMID:36194315DOI:10.1007/s00894-022-05326-1.
Cancer is imposing a global health burden because of the steady increase in new cases. Moreover, current anticancer therapeutics are associated with many drawbacks, mainly the emergence of resistance and the severe adverse effects. Therefore, there is a continuous need for developing new anticancer agents with novel mechanisms of action and lower side effects. Natural products have been a rich source of anticancer medication. Cycleanine, a natural product, was reported to exert an antiproliferative effect on ovarian cancer cells by causing apoptosis through activation of caspases 3/7 and cleavage of poly (ADP-ribose) polymerase to form poly (ADP-ribose) polymerase-1 (PARP1). It is well-established that PARP1 is associated with carcinogenesis, and different PARP1 inhibitors are approved as anticancer drugs. In this study, the cytotoxic activity of Cycleanine was computationally investigated to determine whether it is a PARP1 inhibitor or a caspase activator. Molecular docking and molecular dynamics (MD) simulations were utilized for this purpose. The results showed that Cycleanine has a good binding affinity to PARP1; moreover, MD simulation showed that it forms a stable complex with the enzyme. Consequently, the results showed that Cycleanine is a potential inhibitor of the PARP1 enzyme.
Synthesis of (aminoalkyl)Cycleanine analogues: cytotoxicity, cellular uptake, and apoptosis induction in ovarian cancer cells
Bioorg Med Chem Lett 2018 May 15;28(9):1652-1656.PMID:29588214DOI:10.1016/j.bmcl.2018.03.038.
Our previous studies demonstrated that Cycleanine, a macrocyclic bisbenzylisoquinoline (BBIQ) alkaloid, showed potent anti-ovarian cancer activity via apoptosis induction. Here, we synthesized two novel (aminoalkyl)Cycleanine analogues (2 and 3) through a simple and efficient two-step reaction starting from Cycleanine isolated from Triclisia subcordata Oliv. These analogues showed greater potency than the unmodified Cycleanine in three human ovarian cancer cell lines. Both 2 and 3 induced apoptosis in ovarian cancer cells by activations of caspases 3/7, cleavage of PARP, increase in subG1 cell cycle phase and in the percentage of apoptotic cells. Further confocal fluorescence microscopy analysis confirmed the cellular uptake of alkaloids in ovarian cancer cells by using the unique (alkynyl)Cycleanine (3) via click chemistry reaction. Our results suggest that Cycleanine could be a hit compound for the future development in attacking ovarian cancer.
In Vivo Efficacy and Metabolism of the Antimalarial Cycleanine and Improved In Vitro Antiplasmodial Activity of Semisynthetic Analogues
Antimicrob Agents Chemother 2021 Jan 20;65(2):e01995-20.PMID:33257443DOI:10.1128/AAC.01995-20.
Bisbenzylisoquinoline (BBIQ) alkaloids are a diverse group of natural products that demonstrate a range of biological activities. In this study, the in vitro antiplasmodial activity of three BBIQ alkaloids (Cycleanine [compound 1], isochondodendrine [compound 2], and 2'-norcocsuline [compound 3]) isolated from the Triclisia subcordata Oliv. medicinal plant traditionally used for the treatment of malaria in Nigeria are studied alongside two semisynthetic analogues (compounds 4 and 5) of Cycleanine. The antiproliferative effects against a chloroquine-resistant Plasmodium falciparum strain were determined using a SYBR green 1 fluorescence assay. The in vivo antimalarial activity of Cycleanine is then investigated in suppressive, prophylactic, and curative murine malaria models after infection with a chloroquine-sensitive Plasmodium berghei strain. BBIQ alkaloids (compounds 1 to 5) exerted in vitro antiplasmodial activities with 50% inhibitory concentration (IC50) at low micromolar concentrations and the two semisynthetic Cycleanine analogues showed an improved potency and selectivity compared to those of Cycleanine. At oral doses of 25 and 50 mg/kg body weight of infected mice, Cycleanine suppressed the levels of parasitemia and increased mean survival times significantly compared to those of the control groups. The metabolites and metabolic pathways of Cycleanine were also studied using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Twelve novel metabolites were detected in rats after intragastric administration of Cycleanine. The metabolic pathways of Cycleanine were demonstrated to involve hydroxylation, dehydrogenation, and demethylation. Overall, these in vitro and in vivo results provide a basis for the future evaluation of Cycleanine and its analogues as leads for further development.
Calcium antagonist properties of the bisbenzylisoquinoline alkaloid Cycleanine
Fundam Clin Pharmacol 1998;12(2):182-7.PMID:9565772DOI:10.1111/j.1472-8206.1998.tb00939.x.
The alkaloid Cycleanine ([12aR-(12aR,24aR)]-2,3,12a,13,14,15,24,24a-octa hydro-5,6,17,18- tetramethoxy-1,13-dimethyl-8, 11:20,23-dietheno-1H,12H [1,10]dioxacyclooctadecino[2,3,4-ij:11,12,13-i'j']diisoquinolin e) was extracted from the bulbs of Stephania glabra (Roxb) Miers and its effects on cardiac and smooth muscle preparations were studied and compared to those of nifedipine (1,4-dihydro-2, 6-dimethyl-4-(2-nitrophenyl)-3,5-pyridine dicarboxylic acid dimethylesther). Cycleanine inhibited the KCl-induced contraction of rabbit aortic rings with higher potency than nifedipine. IC50s for Cycleanine and nifedipine were 0.8 and 7.10(-9) M respectively. Cycleanine had minor effects on the norepinephrine-induced contraction of rabbit aortic rings. Cycleanine and nifedipine also depressed the contraction of rat ventricular preparations but with lower potency (IC50 = 3 and 0.03.10(-6) M respectively). Action potential duration of rat right ventricular strips was decreased by both compounds. L-type Ca-current (ICaL) of single rat ventricular cardiomyocytes was inhibited by Cycleanine in a voltage- and frequency-dependent manner. With a higher potency nifedipine inhibited ICaL in a tonic and almost frequency-independent manner. The results suggest that Cycleanine can act as a potent vascular selective Ca-antagonist.
Inhibition of Na(+),K(+)-ATPase by the extract of Stephania cephararantha HAYATA and bisbenzylisoquinoline alkaloid Cycleanine, a major constituent
Biochem Pharmacol 2003 Aug 1;66(3):379-85.PMID:12907236DOI:10.1016/s0006-2952(03)00210-7.
The Stephania cephararantha HAYATA extract, and its constituent bisbenzylisoquinoline alkaloids, such as Cycleanine, cepharanthine, isotetrandrine, berbamine, homoaromoline, and cepharanoline were studied for effects on Na(+),K(+)-ATPase activity. The S. cephararantha HAYATA extract inhibited Na(+),K(+)-ATPase activity with an apparent IC(50) value of 540 microg/mL. Cycleanine markedly inhibited Na(+),K(+)-ATPase activity with an IC(50) value of 6.2 x 10(-4)M. It slightly inhibited Mg(2+)-ATPase, H(+)-ATPase, and Ca(2+)-ATPase. No effects on alkaline and acid phosphatase activities were observed. The inhibition by isotetrandrine, homoaromoline, cepharanthine, and berbamine was less marked, and cepharanoline showed no effect. Five synthetic analogues of cepharanthine slightly inhibited the activity. The mechanism of inhibition by Cycleanine on Na(+),K(+)-ATPase activity was examined in detail, and the following results were obtained in the overall reaction: (1) the mode of inhibition was noncompetitive with respect to ATP; (2) the degree of inhibition was decreased with a decrease of K(+) concentration; (3) it was not affected by Na(+) concentration; (4) the inhibition mechanism was different from that of ouabain. The activity of K(+)-dependent p-nitrophenyl phosphatase, a partial reaction of Na(+),K(+)-ATPase, did not appear to have been inhibited by Cycleanine in the reaction mixture containing 15 mM K(+) (optimum condition). However, Cycleanine increased the K(0.5) value for K(+) and reduced the K(i) values for Na(+) and ATP, in K(+)-dependent p-nitrophenyl phosphatase. Cycleanine might interact with the enzyme in Na.E(1)-P form and prevents the reaction step from Na.E(1)-P to E(2)-P.