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Special Issue "Directed Drug Design and Molecular Therapy"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: 10 July 2018

Special Issue Editor

Guest Editor
Prof. Mahesh Narayan

Department of Chemistry, University of Texas at El Paso (UTEP), El Paso, TX 79968, USA
Website | E-Mail
Interests: protein folding; docking; halogen bonding; reactive oxygen species; neurodegenerative disorders; drug-discovery; chemical education

Special Issue Information

Dear Colleagues,

The field of drug discovery is experiencing a renaissance. It was not long ago that the pharmaceutical giants reported a gloomy outlook, with no new therapeutics coming into the market. Pharma lines had dried with the soils of tropics having being mined bare for some time. The ocean floor represented an avenue, but it was not easy to harvest. However, the overcast forecast propelled the biomedical community to dig deep and looks for alternative avenues to keep the hits coming. Particularly noteworthy in this light were (and continue to be) the efforts to gain traction into better understanding ligand:receptor interactions using in silico approaches. A second avenue is the development of mechanisms to elucidate the dynamics of receptors and the folding forces that are key to their integrity. A third is the use of unnatural atoms in receptors to unravel their biology. A case in point is the extensive use of Selenium atoms in place of cytseine sulfurs to clarify the functional roles of proteins in complex environments. Such steps are pivotal in directed drug design and improve the odds of a successful outcome (hit), rather than the alternative approach of simply screening millions of compounds. Finally, a fourth approach that has emerged on the horizon is that of tailored therapies. This mechanism takes into account the single nucleotide polymorphisms (SNPs) in individuals that compromise therapeutic outcomes. By examining enzymes such as the cytochrome P450 family for polymorphisms and by also profiling the metabolic products of drug candidates as a function of the SNP, a better therapeutic regimen can be designed.

In sum and substance, clearly the ability to resolve, at a molecular level, the chemistry between a biological host and its ligand guest is key towards bettering the biomedical prospects of disease intervention.

Prof. Mahesh Narayan
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • in silico drug-design
  • drug-receptor interaction
  • molecular dynamics
  • single nucleotide polymorphisms

Published Papers (2 papers)

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Research

Open AccessArticle Furan- and Thiophene-2-Carbonyl Amino Acid Derivatives Activate Hypoxia-Inducible Factor via Inhibition of Factor Inhibiting Hypoxia-Inducible Factor-1
Molecules 2018, 23(4), 885; https://doi.org/10.3390/molecules23040885
Received: 9 March 2018 / Revised: 10 April 2018 / Accepted: 10 April 2018 / Published: 11 April 2018
PDF Full-text (10744 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Induction of a series of anti-hypoxic proteins protects cells during exposure to hypoxic conditions. Hypoxia-inducible factor-α (HIF-α) is a major transcription factor that orchestrates this protective effect. To activate HIF exogenously, without exposing cells to hypoxic conditions, many small-molecule inhibitors targeting prolyl hydroxylase
[...] Read more.
Induction of a series of anti-hypoxic proteins protects cells during exposure to hypoxic conditions. Hypoxia-inducible factor-α (HIF-α) is a major transcription factor that orchestrates this protective effect. To activate HIF exogenously, without exposing cells to hypoxic conditions, many small-molecule inhibitors targeting prolyl hydroxylase domain-containing protein have been developed. In addition, suppression of factor inhibiting HIF-1 (FIH-1) has also been shown to have the potential to activate HIF-α. However, few small-molecule inhibitors of FIH-1 have been developed. In this study, we synthesized a series of furan- and thiophene-2-carbonyl amino acid derivatives having the potential to inhibit FIH-1. The inhibitory activities of these compounds were evaluated in SK-N-BE(2)c cells by measuring HIF response element (HRE) promoter activity. Several furan- and thiophene-2-carbonyl amino acid derivatives inhibited FIH-1 based on correlations among the docking score of the FIH-1 active site, the chemical structure of the compounds, and biological HIF-α/HRE transcriptional activity. Full article
(This article belongs to the Special Issue Directed Drug Design and Molecular Therapy)
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Graphical abstract

Open AccessArticle Semisynthesis and Biological Evaluation of Oleanolic Acid 3-O-β-d-Glucuronopyranoside Derivatives for Protecting H9c2 Cardiomyoblasts against H2O2-Induced Injury
Received: 27 October 2017 / Revised: 15 December 2017 / Accepted: 20 December 2017 / Published: 10 January 2018
PDF Full-text (909 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of novel oleanolic acid 3-O-β-d-glucuronopyranoside derivatives have been designed and synthesized. Biological evaluation has indicated that some of the synthesized compounds exhibit moderate to good activity against H2O2-induced injury in rat
[...] Read more.
A series of novel oleanolic acid 3-O-β-d-glucuronopyranoside derivatives have been designed and synthesized. Biological evaluation has indicated that some of the synthesized compounds exhibit moderate to good activity against H2O2-induced injury in rat myocardial cells (H9c2). Particularly, derivative 28-N-isobutyl ursolic amide 3-O-β-d-galactopyranoside (8a) exhibited a greater protective effect than the positive control oleanolic acid 3-O-β-d-glucuronopyranoside, indicating that it possesses a great potential for further development as a cardiovascular disease modulator by structural modification. Full article
(This article belongs to the Special Issue Directed Drug Design and Molecular Therapy)
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Figure 1

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Author: Associate Professor Diannan Lu
Affiliation: Tsinghua University, Beijing, China
Tentative title: The mechanism for the transmembrane delivery of siRNA assisted by PMAL: a Coarse-grained molecular dynamics simulation study
Abstract: The properties of complex of PMAL (poly(maleic anhydride-alt-1-decene) substituted with 3-(dimethylamino) propylamine) and siRNA (Small interfering RNA) has been reported by our previous work. Besides, the promotion of siRNA delivery with the assistance of PMAL has also been discussed. In order to further reveal the potential application of PMAL in gene therapy, screened molecular weight of PMAL (32 units) was chosen to elcuidate transmembrane mechanism. The delivery processes with and without PMAL have been performed using steered molecular dynamics simulation based on martini coarse-grained model. Two pulling rates of 10-6 nm ps-1 and 10-5 nm ps-1 are chosen to imitate the passive and active delivery of siRNA and PMF (potential of mean force) has been calculated in order to real the energy change during the transmembrane process. Moreover, the process of pulling out of PMAL has also been studied to further conform the role of PMAL in siRNA delivery. As a result, we find that only the passive delivery of siRNA with the help of PMAL can be effective. The PMAL can help siRNA insert in membrane and lower the energy barrier for separation, but more energy must be spent because of the interaction between PMAL and siRNA to effectively deliver siRNA through the cell membrane.
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