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Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus.

Author: ChenChin-Ho, DaelemansDirk, De ClercqErik, HuangBoshi, KangDongwei, LeeKuo-Hsiung, LiuJinghan, LiuXinyong, LiuZhaoqiang, PannecouqueChristophe, TianYe, ZhanPeng, ZhangHeng

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Overview

This study focuses on the development and evaluation of novel diarylnicotinamide derivatives with a "triazole tail" as potential HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). These compounds were designed to interact with the NNRTI binding pocket of the reverse transcriptase, aiming for additional interactions within the entrance channel. The synthesized compounds demonstrated good to excellent activity against wild-type HIV-1 strain with EC<sub>50</sub> values ranging from 0.02 to 1.77 µM. Notably, certain compounds effectively inhibited the E138K mutant virus, a key drug-resistant strain to newer generation NNRTIs. Three promising compounds, propionitrile (3b2), pyrrolidin-1-ylmethanone (3b8), and morpholinomethanone (3b9), exhibited potency comparable to the marketed drug Etravirine against the E138K mutant strain, but with significantly lower cytotoxicity.
Paper Details　
Original Abstract of the Article :
Inspired by our previous efforts on the modifications of diarylpyrimidines as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTI) and reported crystallography study, novel diarylnicotinamide derivatives were designed with a "triazole tail" occupying the entrance channel in the NNRTI bindin...See full text at original site
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引用元：
https://pubmed.ncbi.nlm.nih.gov/29635166

データ提供：米国国立医学図書館（NLM）

Diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles: A Novel Class of HIV-1 NNRTIs with High Potency

The fight against HIV continues, and this research explores a promising new class of drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs). NNRTIs work by blocking the activity of reverse transcriptase, an enzyme that HIV uses to replicate itself. This study delves into the development of a novel class of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles, which exhibit potent antiviral activity against HIV-1.

The researchers designed and synthesized these new compounds, incorporating a "triazole tail" that targets a specific region of the reverse transcriptase enzyme. They evaluated the antiviral activity of these compounds against both wild-type and drug-resistant strains of HIV-1.

A Promising New Weapon in the Fight Against HIV

The study revealed that the newly developed diarylnicotinamide derivatives were highly effective against both wild-type and drug-resistant strains of HIV-1. This discovery holds significant promise for developing new treatments for HIV-infected individuals, particularly those who have developed resistance to existing therapies.

Hope on the Horizon

This research offers a glimmer of hope in the ongoing battle against HIV. Just as a camel perseveres through the challenges of the desert, researchers are constantly seeking innovative solutions to combat this devastating virus. The discovery of these potent NNRTIs is a testament to the relentless pursuit of effective treatments for HIV-infected individuals.

Dr.Camel's Conclusion

The development of these novel diarylnicotinamide derivatives represents a significant advancement in the fight against HIV. Their potent antiviral activity against both wild-type and drug-resistant strains offers hope for new treatment options for individuals living with HIV. This research exemplifies the tireless dedication of scientists to find effective solutions to global health challenges.

Date :
  1. Date Completed 2018-05-22
  2. Date Revised 2019-05-10
Further Info :

Pubmed ID

29635166

DOI: Digital Object Identifier

NIHMS961476

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Languages

English

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