Evidence map›Paper›PMID 36738797›Full record

ArticleBioorganic & medicinal chemistry letters2023

Evaluation of darunavir-derived HIV-1 protease inhibitors incorporating P2' amide-derivatives: Synthesis, biological evaluation and structural studies.

Arun K Ghosh, Dana Shahabi, Maya Kipfmiller, Ajay K Ghosh, Megan Johnson, Yuan-Fang Wang, Johnson Agniswamy, Masayuki Amano, Irene T Weber, Hiroaki Mitsuya

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.4field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Arun K GhoshDepartment of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN 47907, USA. Electronic address: akghosh@purdue.edu.
Dana ShahabiDepartment of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Maya KipfmillerDepartment of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Ajay K GhoshDepartment of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Megan JohnsonDepartment of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Yuan-Fang WangDepartment of Biology, Georgia State University, Atlanta, GA 30303, USA.
Johnson AgniswamyDepartment of Biology, Georgia State University, Atlanta, GA 30303, USA.
Masayuki AmanoDepartment of Refractory Viral Diseases, National Center for Global Health and Medicine, Shinjuku, Tokyo 162-8655, Japan; Department of Infectious Diseases, Kumamoto University School of Medicine, Kumamoto 860-8556, Japan.
Irene T WeberDepartment of Biology, Georgia State University, Atlanta, GA 30303, USA.
Hiroaki MitsuyaDepartment of Refractory Viral Diseases, National Center for Global Health and Medicine, Shinjuku, Tokyo 162-8655, Japan; Experimental Retrovirology Section, HIV and AIDS Malignancy Branch National Cancer Institute, Bethesda, MD 20892, USA; Division of Clinical Sciences, Kumamoto University Hospital, Kumamoto 860-8556, Japan.
Georgia State University · USPurdue University West Lafayette · USKumamoto Health Science University · JPNational Center for Global Health and Medicine · JP

Funding

Development of Antiviral Therapy of HIV-1 InfectionZIASC006738 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI MITSUYA, HIROAKI · 2009 to 2025
$10.0M
Design & Synthesis of Nonpeptide Protease InhibitorsR37GM053386 · NIGMS · PURDUE UNIVERSITY · PI GHOSH, ARUN K · 2011 to 2018
$3.9M
DESIGN AND SYNTHESIS OF NONPEPTIDE PROTEASE INHIBITORSR01GM053386 · NIGMS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI GHOSH, ARUN K · 1995 to 2010
$3.7M
Design & Synthesis of Nonpeptide Protease InhibitorsR01AI150466 · NIAID · PURDUE UNIVERSITY · PI ARUN K GHOSH · 2023 to 2026
$2.4M
Design & Synthesis of Nonpeptide Protease InhibitorsR37AI150466 · NIAID · PURDUE UNIVERSITY · PI GHOSH, ARUN K · 2019 to 2020
$969k
Inhibition of Resistant Variants of HIV ProteaseU01AI150461 · NIAID · GEORGIA STATE UNIVERSITY · PI HARRISON, ROBERT WILSON, WEBER, IRENE T · 2019 to 2020
$691k
NIAID NIH HHS R01 AI150466NIAID NIH HHS R37 AI150466NIAID NIH HHS U01 AI150461NIGMS NIH HHS R01 GM053386NIGMS NIH HHS R37 GM053386
6 · The paper itself

Abstract

We report here the synthesis and biological evaluation of darunavir derived HIV-1 protease inhibitors and their functional effect on enzyme inhibition and antiviral activity in MT-2 cell lines. The P2' 4-amino functionality was modified to make a number of amide derivatives to interact with residues in the S2' subsite of the HIV-1 protease active site. Several compounds exhibited picomolar enzyme inhibitory and low nanomolar antiviral activity. The X-ray crystal structure of the chloroacetate derivative bound to HIV-1 protease was determined. Interestingly, the active chloroacetate group converted to the acetate functionality during X-ray exposure. The structure revealed that the P2' carboxamide functionality makes enhanced hydrogen bonding interactions with the backbone atoms in the S2'-subsite.

Indexed as

HIV-1HIV Protease InhibitorsAmidesChloroacetatesCrystallography, X-RayDarunavirDrug DesignHIV ProteaseStructure-Activity RelationshipAmidesChloroacetatesDarunavirHIV ProteaseHIV Protease Inhibitorsp16 protease, Human immunodeficiency virus 1DarunavirHIV-1 proteaseInhibitorSynthesisX-ray structure

Identifiers

PMID36738797
PMCPMC10061991
OpenAlexW4319160507

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.