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HIV-1 RT has been considered as one of the most important targets for the development of anti-HIV-1 drugs for their well-solved three-dimensional structure and well-known mechanism of action. In this study, with HIV-1 RT as target, we used miniaturized parallel click chemistry synthesis via CuAAC reaction followed by in situ biological screening to discover novel potent HIV-1 NNRTIs. A 156 triazole-containing inhibitor library was assembled in microtiter plates and in millimolar scale. The enzyme inhibition screening results showed that 22 compounds exhibited improved inhibitory activity. Anti-HIV-1 activity results demonstrated that A3N19 effected the most potent activity against HIV-1 IIIB (EC = 3.28 nM) and mutant strain RES056 (EC = 481 nM). The molecular simulation analysis suggested that the hydrogen bonding interactions of A3N19 with the main chain of Lys101 and Lys104 was responsible for its potency. Overall, the results indicated the in situ click chemistry-based strategy was rational and might be amenable for the future discovery of more potent HIV-1 NNRTIs.
This article was published in the following journal.
Name: European journal of medicinal chemistry
Click chemistry is fundamentally important to medicinal chemistry and chemical biology. It represents a powerful and versatile tool, which can be exploited to develop novel Pt-based anticancer drugs a...
Magnetic resonance sensing (MRS) assays with simple pretreatment have drawn increasing attention for the development of biosensors, whereas conventional MRS is not competent for analyzing trace target...
This work aimed to undertake the in situ conversion of the terminal amine group of bacterial DFO siderophores, including desferrioxamine B (DFOB), to an azide group to enable downstream click chemistr...
Highly efficient tumor-targeted therapy remains a great challenge due to the complexity and heterogeneity of tumor tissues. Herein, we developed an in vivo two-step tumor-targeting strategy by combini...
Inducible isozyme cyclooxygenase-2 (COX-2) is upregulated under acute and chronic inflammatory conditions, including cancer, wherein it promotes angiogenesis, tissue invasion, and resistance to apopto...
The overarching goal of the proposed Phase II research is to demonstrate the short-term effectiveness of the modification of an existing, effective, computer-based, tobacco prevention prog...
The Click-Mid-Upper Arm Circumference study aims to describe and compare the performance of a set of three simplified mid-upper arm circumference classification devices ("Click-MUAC") for ...
Routine MRI is normal in motor neuron diseases such as ALS. However, advanced MRI techniques can provide an objective measure of degeneration (a "biomarker") by examining brain structure, ...
This is a multicenter study with a minimum of three CLIA-Waived intended operator sites in which prospectively collected vaginal swab specimens will be evaluated with the Click Sexual Heal...
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are commonly included in anti-HIV drug regimens. However, HIV infected women who have previously taken the NNRTI nevirapine (NVP) f...
Organic chemistry methodology that mimics the modular nature of various biosynthetic processes. It uses highly reliable and selective reactions designed to "click" i.e., rapidly join small modular units together in high yield, without offensive byproducts. In combination with COMBINATORIAL CHEMISTRY TECHNIQUES, it is used for the synthesis of new compounds and combinatorial libraries.
A chemistry-based technology in which sets of reactions, for solution or solid-phase synthesis, are used to create molecular libraries for analysis of compounds on a large scale.
A condition in which abnormal cells have not spread outside the duct, lobule, or nipple to other tissues of the breast. There are 3 types of breast carcinoma in situ: DUCTAL CARCINOMA IN SITU; LOBULAR CARCINOMA IN SITU; and PAGET DISEASE OF THE NIPPLE
Experience-based techniques for problem-solving, learning, and discovery that find a solution which is not guaranteed to be optimal, but sufficient for a given set of goals.
A process that searches for hidden and important connections among information embedded in published literature.
Human Immuno Deficiency Virus (HIV)
Human Immunodeficiency Virus (HIV), the causative agent of AIDS. The Human Immunodeficiency Virus, more commonly known as HIV, is a member of the lentivirus sub-set of the retrovirus family of pathogens. It causes AIDS, or Acquired Immuno Deficiency Sy...
Standard antiretroviral therapy (ART) consists of the combination of at least three antiretroviral (ARV) drugs to maximally suppress the HIV virus and stop the progression of HIV disease. Huge reductions have been seen in rates of death and suffering whe...