Cited by 52Computational Drug Discovery MethodsResearch on Leishmaniasis StudiesPhytochemicals and Medicinal Plants

Blocking Protein kinase C signaling pathway: mechanistic insights into the anti-leishmanial activity of prospective herbal drugs from Withania somnifera

Open access
Grover, Abhinav, Katiyar, Shashank Prakash, Jeyakanthan, Jeyaraman, Dubey, Vikash Kumar, Sundar, Durai·2012·BMC Genomics

Abstract

BACKGROUND: Leishmaniasis is caused by several species of leishmania protozoan and is one of the major vector-born diseases after malaria and sleeping sickness. Toxicity of available drugs and drug resistance development by protozoa in recent years has made Leishmaniasis cure difficult and challenging. This urges the need to discover new antileishmanial-drug targets and antileishmanial-drug development. RESULTS: Tertiary structure of leishmanial protein kinase C was predicted and found stable with a RMSD of 5.8Å during MD simulations. Natural compound withaferin A inhibited the predicted protein at its active site with -28.47 kcal/mol binding free energy. Withanone was also found to inhibit LPKC with good binding affinity of -22.57 kcal/mol. Both withaferin A and withanone were found stable within the binding pocket of predicted protein when MD simulations of ligand-bound protein complexes were carried out to examine the consistency of interactions between the two. CONCLUSIONS: Leishmanial protein kinase C (LPKC) has been identified as a potential target to develop drugs against Leishmaniasis. We modelled and refined the tertiary structure of LPKC using computational methods such as homology modelling and molecular dynamics simulations. This structure of LPKC was used to reveal mode of inhibition of two previous experimentally reported natural compounds from Withania somnifera - withaferin A and withanone.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/1471-2164-13-s7-s20

Cites

49 of 49 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Grover A Priyandoko D Gao R Shandilya A Widodo N Bisaria VS Kaul SC Wadhwa R Sundar D Withanone binds to mortalin and abrogates mortalin-p53 complex: Computational and experimental evidence Int J Biochem Cell Biol 2012 44 3 496 504 10.1016/j.biocel.2011.11.021 22155302 · DOI

Cited by

Sorted by citations

Authors
Grover, A., Katiyar, S. P., Jeyakanthan, J., Dubey, V. K., & Sundar, D.
Affiliations
  • Indian Institute of Technology Delhi (IN)
  • Alagappa University (IN)
  • Indian Institute of Technology Guwahati (IN)
Corresponding author
Sundar, Durai
Venue
BMC Genomics
Published
2012-12
Volume
13
Issue
S7
Pages
S20-S20
ISSN
1471-2164 (ISSN-L)
OpenAlex
W1865104699
Cited by
52
References
49
Citations by year
2026: 3 · 2025: 3 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 7 · 2019: 1 · 2018: 6 · 2017: 9 · 2016: 3 · 2015: 6 · 2014: 1 · 2012: 1
FWCI
2.76
Type
journal article
Language
en
Open access
Locations
  • BMC Genomics (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Department of Biotechnology, Ministry of Science and Technology, India
  • Indian Institute of Technology Delhi
Topics
  • Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
  • Health Sciences › Medicine › Complementary and alternative medicine › Phytochemicals and Medicinal Plants
Keywords
leishmaniasis, Withania somnifera, withaferin A, withanone, antileishmanial activity, protein kinase C inhibition, herbal drugs, drug target identification, protein tertiary structure prediction, homology modeling, molecular dynamics simulation, binding free energy
MeSH terms
Antiprotozoal Agents, Binding Sites, Leishmania, Protein Kinase C, Thermodynamics, Triterpenes, Signal Transduction, Protozoan Proteins, Catalytic Domain, Herbal Medicine, Withania, Withanolides, Molecular Docking Simulation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review