- Combretastatin A4 analogue containing cyanoethylene joining chain and application in preparing antitumor drugs
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The invention a Combretastatin A4 analogue containing a cyanoethylene joining chain and an application in preparing antitumor drugs, which relates to the field of a medicinal compound. A structural formula (I-IV) is shown as the specification, an anticancer candidate compound which has strong inhibitory activity against cancer cells and is not toxic to normal cells is currently lacked, for the reason, the method prepares 19 I-IV series compounds, and the para and meta positions of the B ring (benzene ring) introduce various alkyl groups, alkoxy groups or amino substituents or replace the B ring (benzene ring) with various heterocyclic rings. In the I-series compound, when the para position of the B ring (benzene ring) is substituted with an ethyl group, an isopropyl group, a dimethylaminogroup or a diethylamino group, the proliferation resistance of the cancer cells is very strong, and toxicity is weak for the L-02 normal cells, a selective anticancer activity coefficient (an IC50 value ratio of L-02 normal cells to cancer cells) can even exceed 10,000, and the four compounds have the potential to be developed into safe and highly effective anticancer drugs.
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Paragraph 0044; 0054; 0055; 0056
(2019/03/15)
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- Synthesis and pharmacological evaluation of 2,3-diphenyl acrylonitriles-bearing halogen as selective anticancer agents
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Eighteen novel 2,3-diphenyl acrylonitrile derivatives bearing halogens were designed, synthesized, and evaluated for biological activity. Preliminary in vitro results indicated that the majority of the compounds with a para-substituted halogen had considerable antiproliferative activity against five human cancer cell lines, including MGC-803, AGS, and BEL-7402, with IC50 values in the range of 0.46–100?μm. No significant toxic effects on the non-cancerous human liver cell line L-02 were observed. The selective inhibitory activities against cancer cells were significantly better than that of the control lead compound CA-4 and CA-4P. Particularly, potent activities were found for the derivatives of 3-(4-halogen phenyl)-2-(3,4,5-trimethoxyphenyl)acrylonitrile, such as 5c (4-fluoro), 5f (4-bromo), 5h (4-chloro), and 5k (4-trifluoro- methyl), for AGS with IC50 values of 0.75?±?0.24, 0.68?±?0.21, 0.41?±?0.05, and 1.49?±?0.92?μm, respectively. The antiproliferative effects of 5f were attributed to cell-cycle arrest in the G2/M phase, induction of cellular apoptosis, suppression of cell migration, and inhibition of cell colony formation in AGS cells.
- Li, Jia-Jun,Ma, Jun,Xin, Ya-Bing,Quan, Zhe-Shan,Tian, Yu-Shun
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p. 1419 - 1428
(2018/06/06)
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- Synthesis and characterisation of (Z)-styrylbenzene derivatives as potential selective anticancer agents
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To identify anticancer agents with high potency and low toxicity, a series of (Z)-styrylbenzene derivatives were synthesised and evaluated for anticancer activities using a panel of nine cancer cell lines and two noncancerous cell lines. Most derivatives exhibited significant anti-proliferative activities against five cancer cell lines, including MGC-803 and BEL-7402. (Z)-3-(p-Tolyl)-2-(3,4,5-trimethoxyphenyl)acrylonitrile (6h) showed a strong inhibitory effect on MGC-803 cells (IC50 50 50 value of 6h in L-02 cells was 10,000-fold higher than in MGC-803 cells. Compound 6h inhibited proliferation of BEL-7402 cells by arresting at the G2/M phase through up-regulation of cyclin B1 expression, down-regulation of cyclin A and D1 expression, and induction of apoptosis. In addition, 6h inhibited the migration of BEL-7402 cells and the formation of cell colonies.
- Xin, Ya-Bing,Li, Jia-Jun,Zhang, Hong-Jian,Ma, Jun,Liu, Xin,Gong, Guo-Hua,Tian, Yu-Shun
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p. 1554 - 1564
(2018/10/02)
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- Preparation and uses of combretastatin A4 analogs containing cyano and halogen
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The present invention provides preparation and uses of combretastatin A4 analogs containing cyano and halogen, and relates to the field of medicinal compounds, wherein the structure of the combretastatin A4 analog is represented by the following formula defined in the specification. In the prior art, the selective anticancer activity compounds with characteristics of strong inhibition activity oncancer cells and no toxicity to normal cells are necessary to the generation of novel anticancer drugs while the compounds are absent. According to the present invention, based on the requirements inthe prior art, 11 series I combretastatin A4 analogs with fluorine, chlorine, bromine or trifluoromethyl at the ortho position, meta position or para position of the B ring, and 7 series II analogs are synthesized; in the series I compounds, when the para position of the B ring is substituted by fluorine, chlorine, bromine or trifluoromethyl, the good selective anticancer activity can be achieved,and the toxicity to L-02 normal cells is weak; when the para position is substituted by fluorine, chlorine or bromine, a ratio of the IC50 value in AGS cancer cells to the IC50 value in L-02 normal cells is greater than 100; when the para position is substituted by trifluoromethyl, a ratio of the IC50 value in MGC-803 cancer cells to the IC50 value in L-02 normal cells is greater than 100; and the selective anticancer activity of the four compounds is good.
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Paragraph 0033; 0040; 0041
(2018/09/29)
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- TYD1608 with selective anti-cancer activity as well as preparation and application thereof
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The invention provides cyan-containing TYD1608, i.e., (Z)-3-(p-methyl phenyl)-2-(3,4,5-trimethoxyphenyl) acrylonitrile as well as preparation and application thereof, and relates to the field of medicinal compounds with the structure shown in the description. Various anti-cancer medicine in the prior art have the killing capability on cancer cells and also have great toxicity on normal cells; thetreatment of cancer patients is seriously influenced, so that the invention of the medicine with the selective anti-cancer activity on the normal cells is very important. The TYD1608 is synthesized; the compound shows strong proliferation inhibition capability on six kinds of human face cancer cells; in addition, the toxicity on the L-02 normal human liver cells is weak. The IC50 value on the MGC-803 gastric cancer cells is smaller than 0.01 mu M, is better than the clinic common use anti-cancer medicine of taxol; good selective anti-cancer activity is realized. Mechanism study shows that theproliferation inhibition activity of the TYD1608 on BEL-7402 cancer cells is the result of inhibiting the G2/M period in the cell period, inducting early stage and later stage apoptosis, blocking cellmigration, inhibiting cell period relevant protein cyclin A1 and cyclin D1.
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Paragraph 0012; 0013; 0025-0027
(2018/11/22)
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- Anti-acute myeloid leukemia activity of 2-chloro-3-alkyl-1,4-naphthoquinone derivatives through inducing mtDNA damage and GSH depletion
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2-Chloro-3-alkyl-1,4-naphthoquinone derivatives were synthesized and tested as the anti-acute myeloid leukaemia agents. The compound 9b (2-chloro-3-ethyl-5,6,7-trimethoxy-1,4-naphthoquinone) was the most potent toward HL-60 leukaemia cells. In mechanistic study for 9b, the protein levels of mtDNA-specific DNA polymerase γ (poly-γ) and mtDNA transcription factor A (mt-TFA) were decreased after the 24 h treatment, showing the occurrence of mtDNA damage. And 9b triggered cell cycle arrest at S phase accompanied by a secondary block in G2/M phase which had a direct link to the process of mtDNA damage. The dissipations of mitochondrial membrane potential and ATP also proceeded. On the other hand, 9b promoted the generation of ROS and resulted in the oxidation of intracellular GSH to GSSG. This process was coupled to the formation of adduct between 9b and GSH, detected by the UV–Vis spectrum and HRMS analysis. Depletion of GSH by buthionine sulfoximine enhanced ROS level and produced higher cytotoxicity, suggesting GSH was involved in the anti-leukemic mechanism of 9b. Together, our results provide new insights on the molecular mechanism of the derivatives of 2-chloro-1,4-naphthoquinone and 9b might be useful for the further development into an anti-leukemia agent.
- Li, Kun,Yang, Kun,Zheng, Lifang,Li, Yuanyuan,Wang, Qi,Lin, Ruili,He, Dian
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p. 4191 - 4200
(2018/07/21)
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- Synthesis of salidroside analogues and their ability of DPPH radical scavenging activity
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Salidroside is a phenylpropanoid glycoside isolated from Rhodiolarosea L., a traditional Chinese medicinal plant, and has displayed a broad spectrum of pharmacological properties. In this paper, about 22 novel glycosides have been synthesized and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenge activity of each glycoside has been evaluated. 2-(3,4,5-Trihydroxyphenyl)ethyl β-D-galactopyranoside and 3-(3,4,5-trihydroxyphenyl)propyl β-D-glucopyranoside exhibit significant activity prior to salidroside and Vitamin C with EC50 values of 35.85 μM and 36.71 μM, respectively. The results indicate that the phenolic hydroxyl group of these compounds is important for radical scavenging activity and phenyl ring substitution by electron-donating substituents lead to increased antioxidant activity.
- Zheng, Cheng,Guo, Yibing,Meng, Ying,Dou, Sufeng,Shao, Jian,Yang, Yumin
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p. 654 - 664
(2013/07/11)
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- Novel hybrids from lamellarin D and combretastatin A 4 as cytotoxic agents
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A new series of hybrids of lamellarin D and combretastatin A 4, 1,2-diphenyl-5,6-dihydropyrrolo [2,1-a] isoquinolines, were designed as cytotoxic agents based on principles of combination in medicinal chemistry and taking the parent compounds' different anti-proliferative mechanisms into consideration. Twenty-two novel hybrids were synthesized through a convenient route, with a key step of core pyrrole formation and evaluated for their anti-proliferative activities in vitro against K-562, A-549, SMMC-7721, SGC-7901 and HCT-116 cancer cell lines. The results showed that some hybrids had good anti-proliferative activities in low IC50 ranges.
- Shen, Li,Yang, Xiaochun,Yang, Bo,He, Qiaojun,Hu, Yongzhou
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scheme or table
p. 11 - 18
(2010/03/03)
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- Synthesis and biological evaluation of 3,4-diaryl-5-aminoisoxazole derivatives
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A series of cis-restricted 3,4-diaryl-5-aminoisoxazoles have been synthesized and evaluated for their biological activities. Among them, compound 11a and 13a displayed potent cytotoxic activities in vitro against five human cancer cell lines with IC50 values in the low micromolar range and two compounds inhibited tubulin polymerization with IC50 value of 1.8, and 2.1 μM, respectively, similar to that of CA-4. Compound 13a could arrest at the G2/M phase of the cell cycle at the concentration of 0.1 and 1.0 μM and induce apoptosis at 0.1-1.0 μM.
- Liu, Tao,Dong, Xiaowu,Xue, Na,Wu, Rui,He, Qiaojun,Yang, Bo,Hu, Yongzhou
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scheme or table
p. 6279 - 6285
(2011/02/24)
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- Controlled conversion of phenylacetic acids to phenylacetonitriles or benzonitriles using bis(2-methoxyethyl)aminosulfur trifluoride
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A mild, efficient, and practical method for the one-step synthesis of benzonitriles from phenylacetic acids using bis(2-methoxyethyl)aminosulfur trifluoride is described. The reaction was easily extended to the synthesis of the corresponding phenylacetonitriles by inclusion of triethylphosphine.
- Kangani, Cyrous O.,Day, Billy W.,Kelley, David E.
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p. 914 - 918
(2008/09/17)
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- Design, synthesis and antiproliferative activity of tripentones: A new series of antitubulin agents
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Structure-activity relationship studies of a new series of tripentones (thieno[2,3-b]pyrrolizin-8-ones), led us to prepare several derivatives with antiproliferative activities. The most promising 3-(3-hydroxy-4-methoxyphenyl)thieno[2,3-b]pyrrolizin-8-one 20 (leukemia L1210, IC50 = 15 nM) was shown to be a potent inhibitor of tubulin polymerization.
- Lisowski, Vincent,Enguehard, Cecile,Lancelot, Jean-Charles,Caignard, Daniel-Henri,Lambel, Stephanie,Leonce, Stephane,Pierre, Alain,Atassi, Ghanem,Renard, Pierre,Rault, Sylvain
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p. 2205 - 2208
(2007/10/03)
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- Glycerin derivative and its pharmacological use
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A glycerin derivative having the following formula (I) or (I') and a pharmacologically acceptable salt thereof are useful to treat diseases caused by the platelet activating factor. STR1
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- ARYNIC CONDENSATION OF NITRILE ANIONS IN THE PRESENCE OF THE COMPLEX BASE NaNH2-CH3CH2(OCH2CH2)2ONa
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Nitrile anions are easily condensed with aryl halides in the presence of Complex Base NaNH2-CH3CH2(OCH2CH2)2ONa via the intermediate arynes.
- Carre, M. C.,Ezzinadi, A. S.,Zouaoui, M. A.,Geoffroy, P.,Caubere, P.
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p. 3323 - 3330
(2007/10/02)
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- Synthetic Studies on Protoberberine Alkaloids
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Condensation of homoveratrylamine with substituted isochroman-3-ones (3a-c) affords N-β-(3,4-dimethoxyphenethyl)arylacetamides (4a-c).Treatment of 4a-c with POCl3 and subsequent NaBH4 reduction of the reaction products furnish (+/-)-2,3,9,10,11-pentamethoxytetrahydroprotoberberine (2a), (+/-)-12-hydroxymethyl-2,3,9,10,11-pentamethoxytetrahydroprotoberberine (2b) and (+/-) nor coralydine (2c), respectively.Oxidation of 2a with iodine furnishes 2,3,9,10,11-pentamethoxyprotoberberinium salt (1).Carbon-13 NMR assignments of 2c, 3b, 3c, 4b and 4c are also reported.
- Patra, Amarendra,Mukhopadhyay, Prabir K.,Ghosh, Gargi
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p. 173 - 175
(2007/10/02)
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- A novel route for the synthesis of mescaline
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A new plausible synthetic pathway for the synthesis of the peyote alkaloid mescaline in a satisfactory overall yield is reported.
- Nabil Aboul-Enein,Eid
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p. 267 - 270
(2007/10/05)
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