Abstract
The interaction between the HIV-1 transactivator protein Tat and RNA response element (TAR) plays a critical role in HIV-1 transcription. Based on the pharmacophore model of reported inhibitors, a series of novel substituted guanidine indole derivatives was designed, synthesized and evaluated for their in vitro HIV-1 and HIV-2 inhibitory activity using the IIIB strain and ROD strain, respectively. Preliminary biological evaluation indicated that three compounds exhibited marked inhibitory activity against HIV-1 IIIB. Quite unexpectedly, compound a-7 was also endowed with the moderate anti-HIV-2 potency (EC50 = 58.14 µM). In addition, preliminary discussion on the activity results and molecular modeling of these new analogues were presented in this manuscript.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-HIV Agents / chemical synthesis
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Anti-HIV Agents / chemistry
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Anti-HIV Agents / pharmacology*
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Dose-Response Relationship, Drug
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Drug Design*
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Guanidine / chemical synthesis
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Guanidine / chemistry
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Guanidine / pharmacology*
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HIV / drug effects
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HIV / genetics
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HIV / metabolism
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Indoles / chemical synthesis
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Indoles / chemistry
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Indoles / pharmacology*
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Microbial Sensitivity Tests
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Molecular Structure
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Protein Binding / drug effects
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RNA, Viral / chemistry
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RNA, Viral / metabolism*
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Response Elements / genetics*
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Structure-Activity Relationship
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tat Gene Products, Human Immunodeficiency Virus / chemistry
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tat Gene Products, Human Immunodeficiency Virus / metabolism*
Substances
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Anti-HIV Agents
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Indoles
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RNA, Viral
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tat Gene Products, Human Immunodeficiency Virus
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Guanidine