All Info About Chemistry

Publication year: 2010
Source: Bioorganic & Medicinal Chemistry, In Press, Accepted Manuscript, Available online 10 March 2010

Markus, Leibeling , Dennis C., Koester , Martin, Pawliczek , Daniel, Kratzert , Birger, Dittrich , …

Herein we describe the synthesis of highly substituted chromans and isochromans using carbohydrates as starting materials. The key step of our synthetic approach is the annelation of the benzene moiety via a highly efficient Pd-catalyzed domino reaction. This powerful approach led to a small library of highly substituted chromans and isochromans by making use of a variety of different diynes and bromoglycals. We investigated several Pd-catalysts in order to improve the yields and to enlarge the scope of the domino reaction. Furthermore, we elucidated the mechanistic picture of the reaction with isotope-labelling experiments. Most probably the reaction proceeds via an…

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Publication year: 2010
Source: Bioorganic & Medicinal Chemistry, In Press, Accepted Manuscript, Available online 10 March 2010

Bojan, Burja , Tamara, Čimbora-Zovko , Sanja, Tomić , Tihana, Jelušić , Marijan, Kočevar , …

A series of pyrazolone-fused combretastatins and precursors were synthesized and their cytotoxicity as well as antitubulin potential was evaluated. The hydrazide 9f and the pyrazolone-fused combretastatins 12a, 12b and 12c were highly cytotoxic against various tumor cell lines including cisplatin resistant cells. The same compounds were also the best inhibitors of tubulin polymerization. Molecular modeling results showed that they bind the colchicine binding site at the tubulin heterodimer. The hydrazide 9f arrested HeLa cells in the G2/M phase of the cell cycle and strongly affected cell shape and microtubule network.

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Hydrazide 9f is highly cytotoxic against various tumor cells including cisplatin resistant cells. It binds to the colchicine binding site at the tubulin heterodimer and has a strong antitubulin potential.

Publication year: 2010
Source: Bioorganic & Medicinal Chemistry, In Press, Accepted Manuscript, Available online 10 March 2010

Gengo, Kashiwazaki , Toshikazu, Bando , Ken-ichi, Shinohara , Masafumi, Minoshima , Hana, Kumamoto , …

We designed and synthesized human telomere alkylating N-methylpyrrole-N-methylimidazole (PI) polyamide conjugates (1–6). The C-type conjugates 1–3 possessed a chlorambucil moiety at the C terminus, whereas the N-type conjugates 4–6 had one of these moieties at the N terminus. The DNA alkylating activity of these conjugates was evaluated by high-resolution denaturing polyacrylamide gel electrophoresis using a 220 bp DNA fragment containing the human telomere repeat sequence 5′–(GGGTTA)4–3′/5′–(TAACCC)4–3′. C-type conjugates are designed to alkylate the G-rich-strand-containing 5’–GGGTTA–3’ and N-type conjugates were designed to alkylate the complementary C-rich strand-containing 5’–TAACCC–3’ sequence. The difference between conjugates 1–3 and 4–6 lies in the linker region…

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We designed and synthesized human telomere alkylating N-methylpyrrole-N-methylimidazole (PI) polyamide conjugates (1–6). The C-type conjugates 1–3 possessed a chlorambucil moiety at the C terminus, whereas the N-type conjugates 4–6 had one of these moieties at the N terminus. The DNA alkylating activity of these conjugates was evaluated by high-resolution denaturing polyacrylamide gel electrophoresis using a 220 bp DNA fragment containing the human telomere repeat sequence 5′–(GGGTTA)4–3′/5′–(TAACCC)4–3′. C-type conjugates are designed to alkylate the G-rich-strand-containing 5’–GGGTTA–3’ and N-type conjugates were designed to alkylate the complementary C-rich strand-containing 5’–TAACCC–3’ sequence. The difference between conjugates 1–3 and 4–6 lies in the linker region between the polyamide moiety and chlorambucil. Conjugates 1 and 4 efficiently alkylated the 5′–GGTTAGGGTTA–3′ and 5′–CCCTAACCCTAA–3′ sequences, respectively, by recognizing 11 bp in the presence of distamycin A (Dist), in a heterotrimeric manner: one long alkylating polyamide conjugate (1–6) and two short partners (Dist).

Publication year: 2010
Source: Bioorganic & Medicinal Chemistry, In Press, Accepted Manuscript, Available online 9 March 2010

Xiao-Qing, Feng , Zhao-Sen, Zeng , Yong-Hong, Liang , Fen-Er, Chen , Christophe, Pannecouque , …

A series of novel diarylpyrimidine analogues featuring a hydroxyiminomethyl group between the pyrimidine scaffold and the aryl wing I have been synthesized and tested in MT-4 cells culture as non-nucleoside reverse transcriptase inhibitors against human immunodeficiency virus (HIV). Most of these new congeners exhibited moderate to excellent activity against wild-type virus with an EC50 value ranging from 0.569 μM to 0.005 μM. 4-(4-((Hydroxyimino) (3-methoxyphenyl)methyl)pyrimidin-2-ylamino)benzonitrile (12n) was identified as the most active compound of this new series (EC50 = 0.025 μM, SI > 1223) associated with moderate activity against HIV-1 double mutant strains (K103N + Y181C)(EC50 = 8.72 μM) in addition…

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Publication year: 2010
Source: Bioorganic & Medicinal Chemistry, In Press, Accepted Manuscript, Available online 9 March 2010

Arzu, Karakurt , Meral, Özalp , Şamil, Işık , James P., Stables , Sevim, Dalkara

In this study, as a continuation of our research for new (arylalkyl)imidazole anticonvulsant compounds, the design, synthesis and anticonvulsant/antimicrobial activity evaluation of a series of 2-acetylnaphthalene derivatives have been described. Molecular design of the compounds has been based on the modification of nafimidone [1-(2-naphthyl)-2-(imidazol-1-yl)ethanone], which is a representative of the (arylalkyl)imidazole anticonvulsant compounds as well as its active metabolite, nafimidone alcohol (3, 4). In general, these compounds were variously substituted at the alkyl chain between naphthalene and imidazole rings and subjected to some other modifications to evaluate additional structure-activity relationships. The anticonvulsant activity profile of those compounds was determined by…

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As a part of our interest on (arylalkyl)imidazole anticonvulsant compounds we describe herein the design and synthesis of a series of acetylnaphthalene derivatives and evaluation of their anticonvulsant/antimicrobial activities. These compounds were variously substituted at the alkyl chain between naphthalene and imidazole rings. The most potent compounds were the ester derivatives with imidazole ring.

Publication year: 2010
Source: Bioorganic & Medicinal Chemistry, In Press, Accepted Manuscript, Available online 9 March 2010

Phi Hung, Nguyen , Thi Ngoc Anh, Nguyen , Keon Wook, Kang , Derek Tantoh, Ndinteh , Joseph Tanyi, Mbafor , …

During the course of a neuraminidase inhibitor screening program on natural products, four new (6, 8, 11, and 12) and eleven known (1−5, 7, 9−10, and 13−15) pterocarpan derivatives were isolated as active principles from the EtOAc extract of the stem bark of Erythrina abyssinica. Their structures were identified by spectroscopic data analyses. All isolates exhibited significant inhibitory effects on the neuraminidases from Clostridium perfringens and Vibrio cholerae with IC50 values ranging from 1.32 to 77.10 μM and 0.35 to 77.73 μM, respectively. The isolates (1−3, 5−8, 10, and 13−15), which possessed noncompetitive inhibition modes in kinetic studies, showed stronger…

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Four new pterocarpenoid derivatives (6, 8, 11, and 12) and eleven known ones (1–5, 7, 9, 10, and 13–15) were isolated from the stem bark of Erythrina abyssinica. All compounds exhibited strong inhibitory effects on the neuraminidase from Clostridium perfringens and Vibrio cholerae with IC50 values ranging from 1.32 ± 0.2 to 77.10 ± 2.2 μM and 0.35 ± 0.02 to 77.73 ± 11.01 μM, respectively. This finding suggests that E. abyssinica and its constituents, pterocarpanoids, can be considered as promising therapeutic agent in the treatment of bacterial infections.

Publication year: 2010
Source: Bioorganic & Medicinal Chemistry, In Press, Accepted Manuscript, Available online 9 March 2010

Yosuke, Taniguchi , Yusuke, Kurose , Takamasa, Nishioka , Fumi, Nagatsugi , Shigeki, Sasaki

We have previously reported that the 2-amino-6-vinylpurine (AVP) nucleoside exhibits a highly efficient and selective crosslinking reaction toward cytosine and displayed an improved antisense inhibition in cultured cells. In this study, we further investigated the alkyl-connected AVP nucleoside analogs for more efficient crosslinking to the cytosine base (rC) of the target RNA. We synthesized three AVP analogs which connect the 2-amino-6-vinylpurine unit to the 2’-deoxyribose through a methylene, an ethylene or a butylene linker. The ODN incorporating the AVP analog with the methylene or the butylene linker showed a slightly higher crosslinking to the target rC of RNA than the…

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Publication year: 2010
Source: Bioorganic & Medicinal Chemistry, In Press, Accepted Manuscript, Available online 9 March 2010

Claudia, Bello , Michele, Cea , Giovanna Dal, Bello , Anna, Garuti , Ilaria, Rocco , …

Novel -mannosidase inhibitors of the type (2R,3R,4S)-2-({[(1R)-2-hydroxy-1-arylethyl]amino}methyl)pyrrolidine-3,4-diol have been prepared and assayed for their anti-cancer activities. Compound 30 with the aryl group = 4-trifluoromethylbiphenyl inhibits the proliferation of primary cells and cell lines of different origins, irrespective of Bcl-2 expression levels, inducing a G2/Mcell cycle arrest and by modification of genes involved in cell cycle progression and survival.

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The novel α-mannosidase inhibitors 29- 34 act as cell cycle modulators on tumor cells of different origins.

Publication year: 2010
Source: Bioorganic & Medicinal Chemistry, Volume 18, Issue 6, 15 March 2010, Page IFC

[No author name available]

Publication year: 2010
Source: Bioorganic & Medicinal Chemistry, Volume 18, Issue 6, 15 March 2010, Pages 2067-2075

[No author name available]