Evidence map›Paper›PMID 36296435›Full record

ArticleMolecules (Basel, Switzerland)2022

Design, Synthesis, and Investigation of Novel Nitric Oxide (NO)-Releasing Aromatic Aldehydes as Drug Candidates for the Treatment of Sickle Cell Disease.

Boshi Huang, Mohini S Ghatge, Akua K Donkor, Faik N Musayev, Tanvi M Deshpande, Mohammed Al-Awadh, Rana T Alhashimi, Hongmei Zhu, Abdelsattar M Omar, Marilyn J Telen and 4 more

Open access · goldAbstract read
In one paragraph

Article in Molecules (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.9field-weighted citation impact, top 24% 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

6 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Hemoglobin Variants as Targets for Stabilizing Drugs.Molecules (Basel, Switzerland) · 2025
    Review
  3. Review
  4. Article
  5. Review
  6. 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

14 authors at 5 institutions in 3 countries.

Boshi HuangDepartment of Medicinal Chemistry, The Institute for Structural Biology, Drug Discovery and Development, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.
Mohini S GhatgeDepartment of Medicinal Chemistry, The Institute for Structural Biology, Drug Discovery and Development, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.
Akua K DonkorDepartment of Medicinal Chemistry, The Institute for Structural Biology, Drug Discovery and Development, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0002-2563-3002
Faik N MusayevDepartment of Medicinal Chemistry, The Institute for Structural Biology, Drug Discovery and Development, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.
Tanvi M DeshpandeDepartment of Medicinal Chemistry, The Institute for Structural Biology, Drug Discovery and Development, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.
Mohammed Al-AwadhDepartment of Medicinal Chemistry, The Institute for Structural Biology, Drug Discovery and Development, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0002-1126-5886
Rana T AlhashimiDepartment of Medicinal Chemistry, The Institute for Structural Biology, Drug Discovery and Development, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.
Hongmei ZhuDepartment of Medicine, Duke University Health System, Durham NC 27710, USA.
Abdelsattar M OmarDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Alsulaymanyah, Jeddah 21589, Saudi Arabia.ORCID 0000-0002-9825-3465
Marilyn J TelenDepartment of Medicine, Duke University Health System, Durham NC 27710, USA.
Yan ZhangDepartment of Medicinal Chemistry, The Institute for Structural Biology, Drug Discovery and Development, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.
Tim J McMahonDepartment of Medicine, Duke University Health System, Durham NC 27710, USA.ORCID 0000-0002-3404-3223
Osheiza AbdulmalikDivision of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Martin K SafoDepartment of Medicinal Chemistry, The Institute for Structural Biology, Drug Discovery and Development, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0002-9536-1743
Virginia Commonwealth University · USDurham VA Health Care System · USAl-Azhar University · EGChildren's Hospital of Philadelphia · USDuke University Health System · US

Funding

Hemoglobin Modifiers for Sickle Cell Disease TherapyR01MD009124 · NIMHD · VIRGINIA COMMONWEALTH UNIVERSITY · PI SAFO, MARTIN K · 2014 to 2018
$2.1M
Targeted Identification of Dual Acting Antisickling Agents for Sickle Cell Disease TherapyR61HL156158 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI ABDULMALIK, OSHEIZA Y, SAFO, MARTIN K · 2021 to 2022
$1.1M
X-ray Crystallographic Data Collection SystemS10OD021756 · OD · VIRGINIA COMMONWEALTH UNIVERSITY · PI SAFO, MARTIN K · 2017 to 2017
$600k
Targeted Identification of Dual Acting Antisickling Agents for Sickle Cell Disease TherapyR33HL156158 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI ABDULMALIK, OSHEIZA Y, SAFO, MARTIN K · 2023 to 2023
$572k
SNO transport regulates endothelial adhesion of RBCsI01BX003478 · VA · DURHAM VA MEDICAL CENTER · PI TIMOTHY J MCMAHON · 2017 to 2026
–
BLRD VA I01 BX003478National Heart Lung and Blood Institute R61HL156158NHLBI NIH HHS R33 HL156158NHLBI NIH HHS R61 HL156158NIH HHS S10 OD021756NIH HHS S10OD021756NIMHD NIH HHS R01 MD009124NIMHD NIH HHS R01MD009124VA MERIT I01-BX-003478Virginia General Assembly Higher Education Equipment Trust Fund HEETF
6 · The paper itself

Abstract

Sickle cell disease (SCD) is caused by a single-point mutation, and the ensuing deoxygenation-induced polymerization of sickle hemoglobin (HbS), and reduction in bioavailability of vascular nitric oxide (NO), contribute to the pathogenesis of the disease. In a proof-of-concept study, we successfully incorporated nitrate ester groups onto two previously studied potent antisickling aromatic aldehydes, TD7 and VZHE039, to form TD7-NO and VZHE039-NO hybrids, respectively. These compounds are stable in buffer but demonstrated the expected release of NO in whole blood in vitro and in mice. The more promising VZHE039-NO retained the functional and antisickling activities of the parent VZHE039 molecule. Moreover, VZHE039-NO, unlike VZHE039, significantly attenuated RBC adhesion to laminin, suggesting this compound has potential in vivo RBC anti-adhesion properties relevant to vaso-occlusive events. Crystallographic studies show that, as with VZHE039, VZHE039-NO also binds to liganded Hb to make similar protein interactions. The knowledge gained during these investigations provides a unique opportunity to generate a superior candidate drug in SCD with enhanced benefits.

Indexed as

Anemia, Sickle CellHemoglobin, SickleAldehydesAnimalsAntisickling AgentsEstersLamininMiceNitratesNitric OxideAldehydesAntisickling AgentsEstersHemoglobin, SickleLamininNitratesNitric Oxideantiadhesionantisicklingaromatic aldehydescrystal structurehemoglobinnitric oxideoxygen equilibrium curvesickle cell disease

Identifiers

PMID36296435
PMCPMC9610770
OpenAlexW4304806289

What OpenQuestion holds

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LicenceCC BY
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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.