1916-07-0Relevant articles and documents
A new cytotoxic cholestane bisdesmoside from Ornithogalum saundersiae bulbs
Mimaki, Yoshihiro,Kuroda, Minpei,Kameyama, Aiko,Sashida, Yutaka,Hirano, Toshihiko,Oka, Kitaro,Koike, Kazuo,Nikaido, Tamotsu
, p. 1049 - 1050 (1996)
Bioassay-guided fractionation of the MeOH extract of Ornithogalum saundersiae bulbs led to the isolation of a new cholestane bisdcsmoside with potent cytotoxic activities toward leukemia HL-60 and MOLT-4 cells. The structure was deduced mainly from spectroscopic information.
Design, synthesis and biological evaluation of a novel tubulin inhibitor 7a3 targeting the colchicine binding site
Lai, Qinhuai,Wang, Yuxi,Wang, Ruixue,Lai, Weirong,Tang, Liangze,Tao, Yiran,Liu, Yu,Zhang, Ruirui,Huang, Luyi,Xiang, Haotian,Zeng, Shaoxue,Gou, Lantu,Chen, Hao,Yao, Yuqin,Yang, Jinliang
, p. 162 - 179 (2018)
Tubulin inhibitors that target the colchicine binding site continue to emerge as promising anticancer agents. In this study, based on the anti-proliferative activities, a novel tubulin inhibitor 7a3 targeting the colchicine binding site was designed, synthesized, and optimized from a series of novel cis-restricted pyrazole analogues of combretastatin A-4. The structure-activity relationships (SARs) of these newly synthesized compounds are summarized indicating that the methyl substituent at the N1 position and deamination were significantly important for the anti-proliferative efficacy. The optimized compound 7a3 exhibited the ability to arrest the cell cycle in the G2/M phase, induce cell apoptosis, and inhibit cell migration in tumour cells. The results of the immunofluorescence analysis using confocal microscopy and the tubulin polymerization assay revealed that tubulin assembly was disrupted by 7a3 in vitro. Furthermore, the targeting identification of 7a3 was illuminated by solving the crystal structure of 7a3 in complex with tubulin at a resolution of 3.2 ? (PDB code 5Z4U), which confirmed the result of molecular docking and further demonstrated that 7a3 binds to the site of colchicine. Moreover, the pharmacokinetic analysis in mouse plasma showed that 7a3 rapidly reached a peak concentration at 0.25 h after intraperitoneal administration, and the T1/2, Cmax, and AUC0-inf were 1.67 ± 0.28 h, 882 ± 71 ng mL-1, and 1166 ± 129 h ng·mL-1, respectively, after a single-dose administration analysed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). In addition, the in vivo study indicated that 7a3 significantly inhibited the tumour growth of the SK-OV-3 xenograft in a nude mouse model. In conclusion, our study proved 7a3 to be a potential microtubule-targeting drug for cancer therapy. The SARs and mechanism of action studies of 7a3 based on the X-ray co-crystal structure provided insights into the next-generation tubulin inhibitors for cancer therapy.
Biologically active bergenin derivatives from bergenia stracheyi
Siddiq, Farah,Fatima, Itrat,Malik, Abdul,Afza, Nighat,Iqbal, Lubna,Lateef, Mehreen,Hameed, Saira,Khan, Sher Wali
, p. 91 - 98 (2012)
New bergenin derivatives, bergecins A and B (1 and 2, resp.), have been isolated from the AcOEt-soluble fraction of Bergenia stracheyi, along with bergenin (3), and their structures were elucidated on the basis of 1H- and 13C-NMR spectra, and by COSY, HMQC, and HMBC experiments. Compound 2 showed potent inhibitory potential against the enzyme lipoxygenase, while 1 was moderately active. On the other hand, both compounds exhibited significant antioxidant activities in 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay. Copyright
Proton-catalyzed methanolysis and stereoelectronically controlled C-3 epimerization of reserpine
Schiffl,Pindur
, p. 443 - 450 (1986)
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Bauer,Starcke
, p. 167,169 (1934)
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Three novel C-glycosidic ellagitannins, Rhoipteleanins H, I, and J, from Rhoiptelea chiliantha
Jiang, Zhi-Hong,Tanaka, Takashi,Kouno, Isao
, p. 425 - 429 (1999)
Three novel C-glycosidic ellagitannins named rhoipteleanins H (1), I (2), and J (3) were isolated from the fruits and bark of Rhoiptelea chiliantha Diels et Hand.-Mazz. (Rhoipteleaceae), and the structures were elucidated on the basis of detailed spectroscopic analysis and chemical evidence. Rhoipteleanin H possesses a unique cyclopentenone carboxyl moiety, which is probably formed by oxidation and subsequent rearrangement of an aromatic ring of a usual C-glycosidic ellagitannin. Rhoipteleanin I is the first ellagitannin having a hydroxynaphthalene glucoside moiety. Rhoipteleanin J is a dimeric ellagitannin generated by dehydrative coupling between two molecules of a monomeric C-glycosidic ellagitannin and subsequent oxidation of an aromatic ring. From a chemotaxonomic viewpoint, presence of these characteristic ellagitannins in this plant provides a further support for the establishment of the order Rhoipteleales comprising Rhoipteleaceae as the only family.
Design and synthesis of novel parabanic acid derivatives as anticonvulsants
Aboutabl, Mona Elsayed,Hassan, Rasha Mohamed,El-Azzouny, Aida Abdel-Sattar,Aboul-Enein, Mohamed Nabil,Abd-Allah, Walaa Hamada
, (2019)
In this work a set of novel derivatives of parabanic acid 9a-d, 12a-d and 13a-d was synthesized and their anticonvulsant potential was evaluated. All the compounds under investigation exhibited anticonvulsant activity in both scPTZ and MES tests. In phase II anticonvulsant study, the trimethoxy phenyl derivative 9a evoked the highest potency among the tested compounds in scPTZ test. It displayed 1.72- and 17.05-folds activity more than the standard drugs phenobarbital and ethosuximide, respectively. In addition, the margin of safety for compound 9a is better than that of the reference antiepileptic drug ethosuximide. Also, compound 9a was devoid of hepatotoxicity indicated by measurements of serum level of ALT, AST, ALP, albumin and total protein. Furthermore, treatment with compound 9a significantly increased the GABA brain level by 2.56-folds compared to the control value. Additionally, molecular docking was performed on the active site of GABA-AT to clarify the interactions of the most potent compound 9a with the enzyme. In MES test, compound 12a exhibited the most potent activity against electric stimuli-induced seizures with the lowest ED50 = 13.7 mg/kg and protective index >36.5. Both candidates 9a and 12a could be a good starting point to develop new molecules as novel antiepileptic drugs.
Antibacterial and Antiviral Activities of 1,3,4-Oxadiazole Thioether 4H-Chromen-4-one Derivatives
Cao, Xiao,Liu, Fang,Liu, Liwei,Liu, Tingting,Peng, Feng,Wang, Qifan,Xie, Chengwei,Xue, Wei,Yang, Jinsong
, p. 11085 - 11094 (2021/10/01)
Various 1,3,4-oxadiazole thioether 4H-chromen-4-one derivatives were conceived. The title compounds demonstrated striking inhibitory effects againstXac,Psa, andXoo. EC50data exhibited that A8 (19.7 μg/mL) had better antibacterial activity againstXoothan myricetin, BT, and TC. Simultaneously, the mechanism of action of A8 had been verified by SEM. The results of anti-tobacco mosaic virus indicated that A9 had the bestin vivoantiviral effect compared with ningnanmycin. From the data of MST, it could be seen that A9 (0.003 ± 0.001 μmol/L) exhibited a strong binding capacity, which was far superior to ningnanmycin (2.726 ± 1.301 μmol/L). This study shows that the 1,3,4-oxadiazole thioether 4H-chromen-4-one derivatives may become agricultural drugs with great potential.
Cobalt Nanoparticles-Catalyzed Widely Applicable Successive C?C Bond Cleavage in Alcohols to Access Esters
Dai, Wen,Gao, Shuang,Li, Guosong,Luo, Huihui,Lv, Ying,Shang, Sensen,Wang, Lianyue
supporting information, p. 19268 - 19274 (2020/08/26)
Selective cleavage and functionalization of C?C bonds have important applications in organic synthesis and biomass utilization. However, functionalization of C?C bonds by controlled cleavage remains difficult and challenging because they are inert. Herein, we describe an unprecedented efficient protocol for the breaking of successive C?C bonds in alcohols to form esters with one or multiple carbon atoms less using heterogeneous cobalt nanoparticles as catalyst with dioxygen as the oxidant. A wide range of alcohols including inactive long-chain alkyl aryl alcohols undergo smoothly successive cleavage of adjacent ?(C?C)n? bonds to afford the corresponding esters. The catalyst was used for seven times without any decrease in activity. Characterization and control experiments disclose that cobalt nanoparticles are responsible for the successive cleavage of C?C bonds to achieve excellent catalytic activity, while the presence of Co-Nx has just the opposite effect. Preliminary mechanistic studies reveal that a tandem sequence reaction is involved in this process.
