- Design, synthesis and anticancer evaluation of novel 1,3-benzodioxoles and 1,4-benzodioxines
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A new set of 1,3-benzodioxoles and 1,4-benzodioxines was designed and synthesized starting from gallic acid as anticancer agents. The antiproliferative effect of the target compounds was evaluated against a panel of cancer cell lines (HepG2, PC-3, MCF-7 and A549) using MTT assay. The 1,4-benzodioxine derivative 11a manifested broad spectrum effect towards the four tested cancer cell lines (IC50 50 = 6.37 μM. Also, flow cytometeric analysis revealed that compound 11a could induce both early and late stage apoptosis in MCF-7 cell line. Moreover, the ability of this compound to stimulate apoptosis in the latter cell line was further confirmed by: increment of Bax/Bcl-2 ratio, increase the expression of tumor suppressor gene p53, boosting the levels of initiator and executioner caspases as well as raise in the amount of cytochrome C. In addition molecular docking study was accomplished on the colchicine binding site of tubulin (pdb: 1SA0) to illustrate the interactions of the most potent compound 11a to the receptor.
- Abd-Allah, Walaa Hamada,Aboul-Enein, Mohamed Nabil,El-Azzouny, Aida Abdel-Sattar,Hassan, Rasha Mohamed,Salman, Asmaa Mohamed
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- Asymmetric total synthesis of four bioactive lignans using donor-acceptor cyclopropanes and bioassay of (?)- and (+)-niranthin against hepatitis B and influenza viruses
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The asymmetric total synthesis of four lignans, dimethylmatairesinol, matairesinol, (?)-niranthin, and (+)-niranthin has been achieved using reductive ring-opening of cyclopropanes. Moreover, we performed bioassays of the synthesized (+)- and (?)-niranthins using hepatitis B and influenza viruses, which revealed the relationship between the enantiomeric structure and the anti-viral activity of niranthin.
- Karasawa, Daichi,Nishii, Yoshinori,Oshima, Mizuki,Ota, Ryotaro,Shimasaki, Noriko,Watashi, Koichi
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p. 4635 - 4639
(2022/02/19)
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- Design and synthesis of novel parabanic acid derivatives as anticonvulsants
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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.
- Aboutabl, Mona Elsayed,Hassan, Rasha Mohamed,El-Azzouny, Aida Abdel-Sattar,Aboul-Enein, Mohamed Nabil,Abd-Allah, Walaa Hamada
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- Structural Modification of the 3,4,5-Trimethoxyphenyl Moiety in the Tubulin Inhibitor VERU-111 Leads to Improved Antiproliferative Activities
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Colchicine binding site inhibitors (CBSIs) hold great potential in developing new generations of antimitotic drugs. Unlike existing tubulin inhibitors such as paclitaxel, they are generally much less susceptible to resistance caused by the overexpression
- Wang, Qinghui,Arnst, Kinsie E.,Wang, Yuxi,Kumar, Gyanendra,Ma, Dejian,Chen, Hao,Wu, Zhongzhi,Yang, Jinliang,White, Stephen W.,Miller, Duane D.,Li, Wei
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p. 7877 - 7891
(2018/09/12)
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- Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
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The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
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Paragraph 1557
(2015/09/22)
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- Cis -restricted 3-aminopyrazole analogues of combretastatins: Synthesis from plant polyalkoxybenzenes and biological evaluation in the cytotoxicity and phenotypic sea urchin embryo assays
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We have synthesized a series of novel cis-restricted 4,5-polyalkoxydiaryl- 3-aminopyrazole analogues of combretastatins via short synthetic sequences using building blocks isolated from dill and parsley seed extracts. The resulting compounds were tested in vivo in the phenotypic sea urchin embryo assay to reveal their antimitotic and antitubulin effects. The most potent aminopyrazole, 14a, altered embryonic cell division at 10 nM concentration, exhibiting microtubule-destabilizing properties. Compounds 12a and 14a displayed pronounced cytotoxicity in the NCI60 anticancer drug screen, with the ability to inhibit growth of multi-drug-resistant cancer cells.
- Tsyganov, Dmitry V.,Konyushkin, Leonid D.,Karmanova, Irina B.,Firgang, Sergei I.,Strelenko, Yuri A.,Semenova, Marina N.,Kiselyov, Alex S.,Semenov, Victor V.
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p. 1485 - 1491
(2013/09/23)
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- Nitrogen-Containing Biphenyl Compounds, Pharmaceutical Compositions of Same, Preparation Methods and Anti-HIV-1 Uses Thereof
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Nitrogen-containing biphenyl compounds as represented by formula (I), pharmaceutically acceptable salts or derivatives thereof, pharmaceutical compositions, and preparation methods therefore, and anti-HIV-1 use of the compound. Each substituent group in formula (I) is as defined in the description.
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- COMPOSITIONS FOR TREATMENT OF CYSTIC FIBROSIS AND OTHER CHRONIC DISEASES
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The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
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- ANALGESIC THAT BINDS FILAMIN A
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A compound, composition and method are disclosed that can provide analgesia. A contemplated compound has a structure that corresponds to Formula A, wherein A, B, X, R1, R2, R7 and R8, and the dashed lines are defined within.
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Page/Page column 124
(2010/05/14)
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- Isolation, synthesis, and neurite outgrowth-promoting activity of illicinin A from the flowers of Illicium anisatum
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Two new prenylated C6-C3 compounds, illicinin A (1) and (4S)-illicinone I (2), were isolated from the flowers of Illicium anisatum. The structures of the new compounds were elucidated by spectroscopic methods. The absolute structure of (4S)-illicinone I was determined by comparing its CD spectrum and specific rotation with those of (4S)-illicinone A (4). Illicinin A (1) and 4-allyl-2,6-dimethoxy-3-(3-methylbut-2-enyl)phenol (3) were found to exhibit neurite outgrowth-promoting activity at concentrations ranging from 0.1 to 10 μM in primary cultured rat cortical neurons. Illicinin A and its derivatives were synthesized for structure-activity relationship studies by employing sequential Stille reactions to introduce a prenyl and an allyl group to the benzene ring, thereby indicating that an allylphenyl moiety in the molecule of 1 is essential for its neurotrophic properties.
- Takaoka, Shigeki,Takaoka, Noriko,Minoshima, Yuka,Huang, Jian-Mei,Kubo, Miwa,Harada, Kenichi,Hioki, Hideaki,Fukuyama, Yoshiyasu
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experimental part
p. 8354 - 8361
(2009/12/26)
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- The first total synthesis of neohelmanticins A-D, amino derivatives of the 1,2-dihydroxypropane core and biological evaluation
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A concise total synthesis of neohelmanticins A-D has been accomplished in 15 steps starting from commercially available gallic acid. Swern oxidation conditions, a Grignard reaction, Sharpless kinetic resolution, and regioselective ring opening of an epoxide with lithium aluminum hydride (LAH) are the key features to install the basic core, dihydroxy phenyl propane 2. One hydroxyl group of this core was esterified with tiglic acid followed by the oxidation and esterification with corresponding acids to yield neohelmanticins A-D.
- Sreedhar, Eppakayala,Sateesh Chandra Kumar,Venkateswar Reddy,Robinson,Suresh Babu,Madhusudana Rao,Srinivas
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experimental part
p. 440 - 448
(2009/09/06)
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- Synthesis of unsymmetrical biphenyls as potent cytotoxic agents
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Twenty-six unsymmetrical biphenyls were synthesized and evaluated for cytotoxic activity against DU145, A549, KB and KB-Vin tumor cell lines. Three compounds 27, 35 and 40 showed very potent activity against the HTCL panel with an IC50 value range of 0.04-3.23 μM. In addition, fourteen active compounds were all more potent against the drug-resistant KB-Vin cell line than the parental KB cell line. Preliminary SAR analysis indicated that two bulky substituents on the 2,2′-positions of unsymmetrical biphenyl skeleton are necessary and crucial for in vitro anticancer activity, thus providing a good starting point to develop unsymmetrical biphenyls as novel anticancer agents.
- Wu, Gang,Guo, Huan-Fang,Gao, Kun,Liu, Yi-Nan,Bastow, Kenneth F.,Morris-Natschke, Susan L.,Lee, Kuo-Hsiung,Xie, Lan
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scheme or table
p. 5272 - 5276
(2009/05/07)
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- Modulators of ATP-binding cassette transporters
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Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.
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Page/Page column 88
(2008/06/13)
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- Synthesis and anti-proliterative in-vitro activity of two natural dihydrostilbenes and their analogues
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A total synthetic route for two natural dihydrostilbenes with significant cytotoxicity toward human cancer cell lines, (3-(2-(7-methoxybenzo[d][1,3] dioxol-5-yl)ethyl)phenol 1a and 6-(3-hydroxyphenethyl)benzo[d][1,3]dioxol-4-ol 1b), which were isolated from Bulbophyllum odoratissimum Lind1, was developed via Wittig-Horner reaction. The natural products 1a and 1b were obtained in 28% and 20% overall yield, respectively. Additionally, nine analogues, 1c-1k, of the two natural dihydrostilbenes were synthesized and evaluated for their anti-proliferative activity against human SGC-7901, KB and HT-1080 cell lines by MTT assay. The activities of 1c and 1d were in the same range as those of the natural products 1a and 1b.
- Zhang, Wei-Ge,Zhao, Rui,Ren, Jian,Ren, Li-Xiang,Lin, Jin-Guang,Liu, Dai-Lin,Wu, Ying-Liang,Yao, Xin-Sheng
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p. 244 - 250
(2008/02/09)
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- Multi-functionalization of gallic acid towards improved synthesis of α- and β-DDB
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The synthesis of mono-, di- and trisubstituted gallic acids and their ester with similar or different groups including different acetal and ketals is described. Regioselective bromination on two ortho-positions of methyl gallate, which is very crucial for many organic syntheses, was achieved in high yield and purity. The α- and β-DDB were synthesized in high overall yield and purity from the regioselective bromoderivatives.
- Alam, Ashraful,Takaguchi, Yutaka,Ito, Hideyuki,Yoshida, Takashi,Tsuboi, Sadao
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p. 1909 - 1918
(2007/10/03)
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- Efficient synthesis of γ-DDB
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Synthesis of γ-DDB, which is another family member of α-DDB (dimethyl 4,4′-dimethoxy-5,6,5′,6 ′- dimethylenedioxybiphenyl-2,2′- dicarboxylate), is described. The unsymmetric isomer (γ-DDB) was constructed by a linker-directed intramolecular Ullmann coupling reaction, followed by the cleavage of the linker and re-esterification.
- Chang, Junbiao,Guo, Xiaohe,Cheng, Senxiang,Guo, Ruiyun,Chen, Rongfeng,Zhao, Kang
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p. 2131 - 2136
(2007/10/03)
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- Synthesis, separation, and theoretical studies of chiral biphenyl lignans (α- and β-DDB)
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Two biphenyl lignans, α- and β-DDB (1 and 2, respectively) were efficiently synthesized without contamination by other regio-isomers. The different yields of the Ullmann coupling reactions for the synthesis of 1 and 2 were rationalized by calculating steric hindrance, stability, entropy change, and heat-of-formation values. The enantiomers of 1 and 2 were readily separated by HPLC on a chiral stationary phase. Their configurations were assigned based on the Cotton effect of the authentic natural products.
- Chang, Junbiao,Chen, Rongfeng,Guo, Ruiyun,Dong, Chunhong,Zhao, Kang
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p. 2239 - 2246
(2007/10/03)
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- Bis(5-aryl-2-pyridyl) derivatives
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A bis(5-aryl-2-pyridyl) compound represented by formula (1) or a salt thereof: wherein A is a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted aromatic heterocyclic group, and X is a group selected from the group consisting of moieties having formulas (2) to (5): wherein, in formula (2), m is an integer of 1 or 2; in formula (3), n is an integer of 1 to 6; and in formula (4), R is hydrogen or a lower alkyl group and p is an integer of 1 to 6.
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- SUBSTITUTED 4-(1H-BENZIMIDAZOL-2-YL)[1,4]DIAZEPANES USEFUL FOR THE TREATMENT ALLERGIC DISEASES
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The present invention relates to novel 4-(1H-benzimidazol-2-yl)[1,4] diazepane derivatives of formula (1): and stereoisomers thereof, and pharmaceutically acceptable salts thereof which are useful as histamine receptor antagonists and tachykinin receptor antagonist. Such antagonists are useful in the treatment of allergic rhinitis, including seasonal rhinitis and sinusitis; inflammatory bowel diseases, including Crohn's disease and ulcerative colitis; asthma; bronchitis; and emesis.
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- Novel substituted 4-(1H-benzimidazol-2-yl) [1,4]diazepanes useful for the treatment of allergic diseases
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The present invention relates to novel 4-(1H-benzimidazol-2-yl)[1,4]diazepane derivatives of formula and stereoisomers thereof, and pharmaceutically acceptable salts thereof which are useful as histamine receptor antagonists and tachykinin receptor antagonist. Such antagonists are useful in the treatment of allergic rhinitis, including seasonal rhinitis and sinusitis; inflammatory bowel diseases, including Crohn's disease and ulcerative colitis; asthma; bronchitis; and emesis.
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- Substituted 4-(1H-benzimidazol-2-yl)[1,4]diazepanes useful for the treatment of allergic disease
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The present invention relates to novel 4-(1H-benzimidazol-2-yl)[1,4]diazepane derivatives of formula (1): and stereoisomers thereof, and pharmaceutically acceptable salts thereof which are useful as histamine receptor antagonists and tachykinin receptor antagonist. Such antagonists are useful in the treatment of allergic rhinitis, including seasonal rhinitis and sinusitis; inflammatory bowel diseases, including Crohn's disease and ulcerative colitis; asthma; bronchitis; and emesis.
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- Substituted 4-(1H-benzimidazol-2-yl-amino)piperidines useful for the treatment of allergic diseases
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The present invention relates to novel substituted piperidine derivatives of formula (1), stereoisomers thereof, and pharmaceutically acceptable salts thereof which are useful as histamine receptor antagonists and tachykinin receptor antagonist. Such antagonists are useful in the treatment of allergic rhinitis, including seasonal rhinitis and sinusitis; inflammatory bowel diseases, including Crohn's disease and ulcerative colitis; asthma; bronchitis; and emesis.
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- Novel biphenyl derivative and preparation and use thereof
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The present invention relates to a novel biphenyl derivative having a liver ailment-moderating action and effective as a remedy for acute hepatitis and chronic hepatitis, a process for the preparation of this biphenyl derivative and a liver ailment-moderating agent comprising this diphenyl derivative as an effective ingredient. This diphenyl derivative is represented by the following formula: STR1 wherein R0 and R1 independently stand for a lower alkyl group or R0 and R1 together represent a group O=C2 stands for an alkyl group having 1 to 3 carbon atoms, and R3 and R4 independently stand for a hydrogen atom or a lower alkyl group.
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- The total synthesis of (±)-megaphyllone acetate, a cytotoxic neolignan
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Conversion of 3-methoxy-4,5-methylenedioxybenzaldehyde into (2RS,3SR,4RS)-2-methoxycarbonyl-4-(3-methoxy-4,5-methylenedioxyphenyl)-3-m ethyl-4-butanolide was carried out in seven steps via 1-acetoxy-1-(3-methoxy-4,5-methylenedioxyphenyl)propanone. The butanolide was further converted into (2RS,3SR,3aRS,5RS)-3,3a,4,5-tetrahydro-5-methoxy-2-(3-methoxy-4,5-methylen edioxyphenyl)-3-methyl-3a-(2-propenyl)-6(2H)-benzofuranone (22) in eight steps. Reduction of 22 with lithium aluminium hydride followed by acetylation with acetic anhydride in pyridine afforded (±)-megaphyllone acetate.
- Matsumoto,Imai,Yamaguchi,et al.
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p. 346 - 351
(2007/10/02)
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- Structure Reinvestigation of Conyzorigun, a New Chromone from Ageratum conyzoides
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A highly oxygenated chromone, conyzorigun (1), from Ageratum conyzoides plants was earlier reported to contain a novel stable ketene acetal system by virtue of an oxygen linkage between the benzopyrone and phenyl moieties.A reinvestigation of this structure in the light of biosynthetic experiments followed by chemical degradation is now described.The results obtained indicate that conyzorigun does not contain the above-described oxygen linkage, being a flavone of a known structure, viz. eupalestin (4).
- Vyas, Ashok V.,Mulchandani, Mewand B.
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p. 2945 - 2947
(2007/10/02)
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