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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...

Graphical abstract

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 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.

Graphical abstract

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

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...

Graphical abstract

Journal of Medicinal Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable).

Journal of Medicinal Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable).

Journal of Medicinal Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable).

Synthesis null; null: 1058-1058
DOI: 10.1055/s-0029-1218689

© Georg Thieme Verlag, Rüdigerstr. 14, 70469 Stuttgart, Germany. All rights reserved. This journal, including all individual contributions and illustrations published therein, is legally protected by copyright for the duration of the copyright period. Any use, exploitation or commercialization outside the narrow limits set by copyright legislation, without the publisher's consent, is illegal and liable to criminal prosecution. This applies in particular to photostat reproduction, copying, cyclostyling, mimeographing or duplication of any kind, translating, preparation of microfilms, and electronic data processing and storage.

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Synthesis null; null: 892-892
DOI: 10.1055/s-0029-1218680

© Georg Thieme Verlag, Rüdigerstr. 14, 70469 Stuttgart, Germany. All rights reserved. This journal, including all individual contributions and illustrations published therein, is legally protected by copyright for the duration of the copyright period. Any use, exploitation or commercialization outside the narrow limits set by copyright legislation, without the publisher's consent, is illegal and liable to criminal prosecution. This applies in particular to photostat reproduction, copying, cyclostyling, mimeographing or duplication of any kind, translating, preparation of microfilms, and electronic data processing and storage.

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Synthesis null; null: A22-A32
DOI: 10.1055/s-0029-1219446

© Georg Thieme Verlag, Rüdigerstr. 14, 70469 Stuttgart, Germany. All rights reserved. This journal, including all individual contributions and illustrations published therein, is legally protected by copyright for the duration of the copyright period. Any use, exploitation or commercialization outside the narrow limits set by copyright legislation, without the publisher's consent, is illegal and liable to criminal prosecution. This applies in particular to photostat reproduction, copying, cyclostyling, mimeographing or duplication of any kind, translating, preparation of microfilms, and electronic data processing and storage.

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Synthesis
DOI: 10.1055/s-0029-1218696

Abstract

A highly efficient synthesis of substituted diarylsilanes is presented. The treatment of substituted arylbromides with -butyllithium in diethyl ether at -78 ˚C, followed by the addition to dichlorodiethoxysilane at the same temperature, leads to the quantitative formation of diaryldiethoxysilane. Selective substitution of the chlorine atoms allows an aqueous work up in air. Subsequently, the diaryldiethoxysilane is reduced to the corresponding diarylsilane by stirring with lithium aluminum hydride in diethyl ether. The product is purified by bulb-to-bulb distillation. This method does not lead to any mono- or tri-substituted products and avoids hand­ling gaseous and explosive dichlorosilane, which is a significant advantage over previously reported procedures.
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