288590-35-2Relevant academic research and scientific papers
Inhibition of HIV-1 integrase-catalysed reaction by new DNA minor groove ligands: The oligo-1,3-thiazolecarboxamide derivatives
Ryabinin, Vladimir A.,Sinyakov, Alexander N.,De Soultrait, Vaea Richard,Caumont, Anne,Parissi, Vincent,Zakharova, Olga D.,Vasyutina, Elena L.,Yurchenko, Ekaterina,Bayandin, Roman,Litvak, Simon,Tarrago-Litvak, Laura,Nevinsky, Georgy A.
, p. 989 - 1000 (2007/10/03)
Human immunodeficiency virus type 1 (HIV-1) integrase (IN) is an essential enzyme in the life cycle of the retrovirus, responsible for catalysing the insertion of the viral genome into the host cell chromosome. For this reason it provides an attractive target for antiviral drug design. We synthesized a series of novel thiazole (Tz)-containing oligopeptides (TCOs; oligo-1,3-thiazolecarboxamides), specifically interacting within the minor groove of DNA. The oligocarboxamide derivatives contained 1-4 Tz rings and different N- and C-terminal groups. The effect of these oligocarboxamides on the HIV-1 IN-catalysed reaction was investigated. Some of the compounds were able to inhibit the reaction. The inhibitory effect of the TCOs increased with the number of Tz units. The structure of various additional positively and/or negatively charged groups attached to the N- and C-termini of TCOs had a pronounced effect on their interaction with the DNA substrate complexed to IN. Modified TCOs having a better affinity for this complex should provide a rationale for the design of drugs targeting the integration step. (C) 2000 Editions scientifiques et medicales Elsevier SAS.
Synthesis and evaluation of oligo-1,3-thiazolecarboxamide derivatives as HIV-1 reverse transcriptase inhibitors
Ryabinin, Vladimir A.,Zakharova, Olga D.,Yurchenko, Ekaterina Y.,Timofeeva, Olga A.,Martyanov, Igor V.,Tokarev, Andrei A.,Belanov, Eugeny F.,Bormotov, Nikolai I.,Tarrago-Litvak, Laura,Andreola, Marie Line,Litvak, Simon,Nevinsky, Georgy A.,Sinyakov, Alexander N.
, p. 985 - 993 (2007/10/03)
A set of oligo-1,3-thiazolecarboxamide derivatives able to interact with the minor groove of nucleic acids was synthesized. These oligopeptides contained different numbers of thiazole units presenting dimethylaminopropyl or EDTA moieties on the C-terminus, and aminohexanoyl or EDTA moieties on the N-terminus. The inhibition of such compounds on HIV-1 reverse transcriptase activity was evaluated using different model template-primer duplexes: DNA·DNA, RNA·DNA, DNA·RNA and RNA·RNA. The biological properties of the thiazolecarboxamide derivatives were compared to those of distamycin, another minor groove binder which contains three pyrrole rings. Similar to distamycin, the thiazole containing oligopeptides were good inhibitors of the reverse transcription reaction in the presence of DNA·DNA. But in contrast to distamycin, the oligothiazolide derivatives were able to inhibit reverse transcription in the presence of RNA·DNA or DNA·RNA template-primers. Both distamycin and oligothiazolecarboxamides had low affinity for RNA·RNA duplexes. The inhibition obtained with the newly synthesized thiazolecarboxamides showed that these compounds were more powerful and versatile inhibitors of the RT-dependent polymerization than the natural minor groove binder distamycin. (C) 2000 Elsevier Science Ltd.
