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Molecular Targeted Peptides/Chemicals as New Pharmacological Tool in Medicine

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biophysics".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 12000

Special Issue Editor


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Guest Editor
EBRI ‘Rita Levi-Montalcini’ Foundation, Rome, Italy
Interests: cell permeable peptides; small molecules; targeted peptides; antibodies; drug developing strategies

Special Issue Information

Dear Colleagues,

As we all know the pharmaceutical market has been mainly characterized by active principle ingredients showing a pharmacology activity for a specific pathology but most of the time the molecular mechanism associated with its activity is not clear.

This describes, in principle, the old pharmacology framework in which several drugs have been identified in serendipity way to directly curative several pathologies. It is known that most of the drugs in the market have been derived mostly from the observation of the efficacy of plants on several pathologies. Now, the hypothetic way of developing a new drug should follow the basic research, identification of molecular targets, and preparation of potential drug leads able to interact with the molecular target.

The research field has become much more sophisticated, with opportunities to study new therapeutic approaches in a more specific way as it is shown from newly published molecules, such as cell-permeable peptides (CPPs), targeted peptides, small molecules, antibodies, etc.

Therefore, this Special Issue will publish cutting-edge research in this field and so we are calling for contributions from any authors active in this field.

Dr. Marco Feligioni
Guest Editor

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Keywords

  • Cell permeable peptides
  • Small molecules
  • Targeted peptides
  • Antibodies
  • Drug developing strategies

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Published Papers (2 papers)

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Research

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21 pages, 2871 KiB  
Article
Setup and Validation of a Reliable Docking Protocol for the Development of Neuroprotective Agents by Targeting the Sigma-1 Receptor (S1R)
by Giacomo Rossino, Marta Rui, Luca Pozzetti, Dirk Schepmann, Bernhard Wünsch, Daniele Zampieri, Giorgia Pellavio, Umberto Laforenza, Silvia Rinaldi, Giorgio Colombo, Laura Morelli, Pasquale Linciano, Daniela Rossi and Simona Collina
Int. J. Mol. Sci. 2020, 21(20), 7708; https://doi.org/10.3390/ijms21207708 - 18 Oct 2020
Cited by 7 | Viewed by 3072
Abstract
Sigma-1 receptor (S1R) is a promising molecular target for the development of novel effective therapies against neurodegenerative diseases. To speed up the discovery of new S1R modulators, herein we report the development of a reliable in silico protocol suitable to predict the affinity [...] Read more.
Sigma-1 receptor (S1R) is a promising molecular target for the development of novel effective therapies against neurodegenerative diseases. To speed up the discovery of new S1R modulators, herein we report the development of a reliable in silico protocol suitable to predict the affinity of small molecules against S1R. The docking method was validated by comparing the computational calculated Ki values of a test set of new aryl-aminoalkyl-ketone with experimental determined binding affinity. The druggability profile of the new compounds, with particular reference to the ability to cross the blood–brain barrier (BBB) was further predicted in silico. Moreover, the selectivity over Sigma-2 receptor (S2R) and N-methyl-d-aspartate (NMDA) receptor, another protein involved in neurodegeneration, was evaluated. 1-([1,1’-biphenyl]-4-yl)-4-(piperidin-1-yl)butan-1-one (12) performed as the best compound and was further investigated for acetylcholinesterase (AchE) inhibitor activity and determination of antioxidant activity mediated by aquaporins (AQPs). With a good affinity against both S1R and NMDA receptor, good selectivity over S2R and favorable BBB penetration potential together with its AChE inhibitory activity and its ability to exert antioxidant effects through modulation of AQPs, 12 represents a viable candidate for further development as a neuroprotective agent. Full article
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Review

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35 pages, 1379 KiB  
Review
Obstacles against the Marketing of Curcumin as a Drug
by Kambiz Hassanzadeh, Lucia Buccarello, Jessica Dragotto, Asadollah Mohammadi, Massimo Corbo and Marco Feligioni
Int. J. Mol. Sci. 2020, 21(18), 6619; https://doi.org/10.3390/ijms21186619 - 10 Sep 2020
Cited by 70 | Viewed by 8296
Abstract
Among the extensive public and scientific interest in the use of phytochemicals to prevent or treat human diseases in recent years, natural compounds have been highly investigated to elucidate their therapeutic effect on chronic human diseases including cancer, cardiovascular disease, and neurodegenerative disease. [...] Read more.
Among the extensive public and scientific interest in the use of phytochemicals to prevent or treat human diseases in recent years, natural compounds have been highly investigated to elucidate their therapeutic effect on chronic human diseases including cancer, cardiovascular disease, and neurodegenerative disease. Curcumin, an active principle of the perennial herb Curcuma longa, has attracted an increasing research interest over the last half-century due to its diversity of molecular targets, including transcription factors, enzymes, protein kinases, growth factors, inflammatory cytokines, receptors, and it’s interesting pharmacological activities. Despite that, the clinical effectiveness of the native curcumin is weak, owing to its low bioavailability and rapid metabolism. Preclinical data obtained from animal models and phase I clinical studies done in human volunteers confirmed a small amount of intestinal absorption, hepatic first pass effect, and some degree of intestinal metabolism, might explain its poor systemic availability when it is given via the oral route. During the last decade, researchers have attempted with new pharmaceutical methods such as nanoparticles, liposomes, micelles, solid dispersions, emulsions, and microspheres to improve the bioavailability of curcumin. As a result, a significant number of bioavailable curcumin-based formulations were introduced with a varying range of enhanced bioavailability. This manuscript critically reviews the available scientific evidence on the basic and clinical effects and molecular targets of curcumin. We also discuss its pharmacokinetic and problems for marketing curcumin as a drug. Full article
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