- Molecular modeling, synthesis and biological evaluation of N-heteroaryl compounds as reverse transcriptase inhibitors against HIV-1
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Different N-heteroaryl compounds bearing pyrimidine and benzimidazole moieties have been designed in silico using Discovery studio 2.5 software, synthesized and evaluated for their inhibitory activity as reverse transcriptase inhibitors against HIV-1 replication using laboratory adapted strains HIV-1IIIB (X4, subtype B) and HIV-1Ada5 (R5, subtype B), and the primary isolates HIV-1UG070 (X4, subtype D) and HIV-1VB59 (R5, subtype C). Cell-based assay showed that compounds were active at 1.394 μM concentrations (Selectivity Index: 1.29-38.39). The studies on structure-activity relationship clearly suggested anti-HIV activity of pyrimidine and benzimidazole derivatives and these findings were consistent with the in vitro cell-based experimental data. The results of molecular modeling and docking confirmed that all compounds assumed a butterfly-like conformation and showed H-bond, 'π-π' and 'π-+' and hydrophobic interactions within flexible non-nucleoside inhibitor binding pocket of HIV-1 reverse transcriptase, similar to known non-nucleoside reverse transcriptase inhibitors, such as nevirapine. In view of the results obtained, it can be said that the chemical skeletons of N, N′-bis-(pyridin-2-yl)-succinamide (14 and 15) and 1, 4-bis-benzoimidazol-1-yl-butane-1, 4-dione (16 and 17) may be used for developing potent inhibitors of HIV-1 replication, with suitable structure/pharmacophore modifications.
- Singh, Anuradha,Yadav, Dipti,Yadav, Madhu,Dhamanage, Ashwini,Kulkarni, Smita,Singh, Ramendra K.
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- Synthesis and biological evaluation of novel PET tracers [18F]AG120 & [18F]AG135 for imaging mutant isocitrate dehydrogenase 1 expression
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Mutations in isocitrate dehydrogenase 1 (IDH1) are commonly found in various human malignancies. Inhibitors of several mutant IDH1 enzymes have entered clinical trials as target therapeutic drugs for the treatment of patients with IDH1 mutations. Herein, we report the synthesis and evaluation of two 18F-labeled tracers, [18F]AG120 and [18F]AG135 for imaging expression of mutated IDH1 in positron emission tomography (PET). [18F]AG120 and [18F]AG135 were synthesized in decay-corrected radiochemical yield of 1 % and 3 %, respectively, high molar activity (52–66 MBq/nmol and 216–339 MBq/nmol, respectively) and high radiochemical purity (>99%). Both tracers showed good in vitro stability, selective uptake into mutated IDH1-expressing cells and good pharmacokinetic profiles with low uptake in most organs/tissues. Furthermore, [18F]AG120 micro-PET/CT imaging displayed significantly greater uptake in IDH1-mutant than in wild-type tumors, Relatively, uptake of [18F]AG135 was observed neither in IDH1-mutant tumor xenografts nor in wild-type tumors. This study suggests that [18F]AG120 is a promising radiotracer for PET imaging of IDH1 mutation, However, further optimization and investigation are necessary for [18F]AG135 due to the limited uptake in mutated IDH1-expressing tumors.
- Cheng, Dengfeng,Cheng, Yuan,Fu, Zhequan,Lin, Qingyu,Shi, Dai,Shi, Hongcheng,Tan, Hui,Wang, Tingting,Xu, Zhan,Zhang, Yingying
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- Analgesic and anti-inflammatory activity of new analogs of HC-030031: A TRPA1 channel antagonist
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One of our study direction is research in the group of compounds affecting the TRPA1 ion channel (Transient receptor potential cation channel, subfamily A, member 1) which can perform an important function in pain (including neuropathic pain) and inflamma
- Kazek, Grzegorz,?lusarczyk, Marietta,Bry?a, Adrian,Ch?o-Rzepa, Gra?yna,Zygmunt, Ma?gorzata
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p. 113 - 119
(2020/04/09)
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- A benzimidazole compound and its preparation method and application
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Provided are 2-substituted-N-[5-(2-(N-aryl methylene)amino-1,3,4-thiadiazole)-methylene]-benzimidazole and a preparation method and an application thereof. The preparation method comprises the steps: firstly, with a benzimidazole compound and potassium chloroacetate as raw materials and ethanol as a solvent, carrying out a reflux reaction to obtain a 1-carboxymethyl-benzimidazole compound; then with polyphosphoric acid, the 1-carboxymethyl-benzimidazole compound and thiosemicarbazide as raw materials, carrying out a reflux reaction to obtain 2-substituted-N-[5-(2-amino-1,3,4-thiadiazole)-methylene]-benzimidazole; then with 2-substituted-N-[5-(2-amino-1,3,4-thiadiazole)-methylene]-benzimidazole, aromatic aldehyde and p-toluenesulfonic acid as raw materials, carrying out a solid-phase reaction, and thus obtaining 2-substituted-N-[5-(2-(N-aryl methylene)amino-1,3,4-thiadiazole)-methylene]-benzimidazole. The preparation method has the advantages of simple reaction process, low equipment requirements, simple operation, relatively high target product yield, and small environmental pollution, and the prepared 2-substituted-N-[5-(2-(N-aryl methylene)amino-1,3,4-thiadiazole)-methylene]-benzimidazole can be applied in preparation of drugs inhibiting escherichia coli.
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Paragraph 0088
(2017/08/25)
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- Ramoplanin derivatives possessing antibacterial activity
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Novel ramoplanin derivatives are disclosed. These ramoplanin derivatives exhibit antibacterial activity. As the compounds of the subject invention exhibit potent activities against gram positive bacteria, they are useful antimicrobial agents. Methods of synthesis and of use of the compounds are also disclosed.
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Page/Page column 57
(2010/11/23)
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- Hetrocyclic systems containing azindole: Synthesis and pharmacological screening of 1-(H/bromo/chloro/nitro/methyl substituted phenyloxy)acetyl/propionyl>benzimidazoles
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Benzimidazole on treatment with α-chloroacetic or propionic acid gives benzimidazole-1-acetic or propionic acid (1a/1b) which on refluxing with thionyl chloride affords the corresponding chloride (2a/2b).The chlorides 2a,b react with bromo, chloro, nitro
- Halwe, Kirti,Srivastava, Santosh Kumar
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p. 710 - 713
(2007/10/02)
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- Antiarteriosclerotic substituted benzimidazol-2-yl-and 3H-imidazo[4,5-b]pyridin-2-yl-phenoxy-alkanoic acids and salts and esters thereof
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Novel substituted benzimidazol-2-yl-phenoxyalkanoic acids, salts and esters thereof and 3H-imidazo[4,5-b]pyridin-2-yl phenoxy-alkanoic acid, salts, and esters which are useful as antiarteriosclerotic agents are disclosed. The compounds elevate the high density lipoprotein fraction of cholesterol and also lower the low density lipoprotein fraction of cholesterol. Methods for preparing and using the compounds are included.
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