Design, Synthesis, Molecular Modeling Study and Biological Evaluation of New N'-Arylidene-pyrido [2,3-<i>d</i>]pyrimidine-5-carbohydrazide Derivatives as Anti-HIV-1 Agents
| Author | Elnaz Ebrahimzadeh | en |
| Author | Seyyed Abbas Tabatabai | en |
| Author | Rouhollah Vahabpour | en |
| Author | Zahra Hajimahdi | en |
| Author | Afshin Zarghi | en |
| Issued Date | 2019-12-31 | en |
| Abstract | In an attempt to identify potential new agents that are active against HIV-1, a series of novel pyridopyrimidine-5-carbohydrazide derivatives featuring a substituted benzylidene fragment were designed and synthesized based on the general pharmacophore of HIV-1 integrase inhibitors. The cytotoxicity profiles of these compounds showed no significant toxicity to human cells and they exhibited anti-HIV-1 activity with EC50 values ranging from 90 to 155 µM. Compound 5j bearing 4-methylbenzylidene group was found to be the most active compound with EC50 = 90 µM and selectivity index, CC50/EC50 = 6.4. Molecular modeling studies indicated the capacity of compound 5j to interact with two Mg2+ cations and several residues that are important in HIV-1 integrase inhibition. These findings suggested that pyridopyrimidine-5-carbohydrazide scaffold might become a promising template for development of novel anti-HIV-1 agents. | en |
| DOI | https://doi.org/10.22037/ijpr.2019.112198.13597 | en |
| URI | https://brieflands.com/journals/ijpr/articles/124681 | en |
| Keyword | Synthesis | en |
| Keyword | Pyridopyrimidine-5-carbohydrazide | en |
| Keyword | HIV-1 integrase | en |
| Keyword | Molecular modeling | en |
| Keyword | Anti-HIV-1 | en |
| Publisher | Brieflands | en |
| Title | Design, Synthesis, Molecular Modeling Study and Biological Evaluation of New N'-Arylidene-pyrido [2,3-<i>d</i>]pyrimidine-5-carbohydrazide Derivatives as Anti-HIV-1 Agents | en |
| Type | Original Article | en |
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