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Special Issue "Small Molecule Catalysts with Therapeutic Potential"

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

Deadline for manuscript submissions: 4 December 2017

Special Issue Editor

Guest Editor
Prof. Dr. Claus Jacob

Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, D-66123 Saarbruecken, Germany
Website | E-Mail
Phone: 00496813023129
Interests: intracellular thiolstat; natural nanoparticles, reactive sulfur species; redox modulation; selenium; sensor/effector catalysts

Special Issue Information

Dear Colleagues,

Most diseases, from trivial infections to serious inflammation and proliferative disorders, exhibit characteristic intracellular disturbances that are notably absent under normal, healthy conditions. These small but significant biochemical differences in metabolites, such as Reactive Oxygen Species (ROS), pH, or other biomolecules, may enable us to selectively target such disorders. Here, catalysts provide an interesting lead, as they combine high efficiency with considerable selectivity, i.e., are able to “sense” the presence of particular metabolites, such as increased concentrations of ROS in the cell, and selectively develop their activity in the presence, but not in the absence, of such substrates. Placed in a living system, catalysts therefore may well metamorphose into intelligent “sensor/effector” agents, which (a) on their own are virtually inactive, (b) are able to recognize the presence of suitable biochemical substrates and hence distinguish between different cells, (c) act in low to sub-micromolar concentrations, and (d) affect the target cell in a highly-efficient manner.

Indeed, during the last decade, various small molecule catalysts with impressive biological activities and considerable pharmaceutical promise have been reported in the literature. It is now time to take stock of these developments and to consider the chemistry, biochemical action and overall activity of various types of small molecule catalysts, and the kind of disorders they may be employed against. This Special Issue will, therefore, bring together researchers and research from different disciplines focussing on such catalytic agents, and their ability to selectively target certain diseases.

Prof. Dr. Claus Jacob
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

  • catalyst
  • redox modulation
  • sensor/effector agent
  • selectivity
  • therapeutic activity

Published Papers (2 papers)

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Research

Open AccessCommunication Cinnamic Acid Analogs as Intervention Catalysts for Overcoming Antifungal Tolerance
Molecules 2017, 22(10), 1783; doi:10.3390/molecules22101783
Received: 28 September 2017 / Revised: 18 October 2017 / Accepted: 19 October 2017 / Published: 21 October 2017
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Abstract
Disruption of fungal cell wall should be an effective intervention strategy. However, the cell wall-disrupting echinocandin drugs, such as caspofungin (CAS), cannot exterminate filamentous fungal pathogens during treatment. For potency improvement of cell wall-disrupting agents (CAS, octyl gallate (OG)), antifungal efficacy of thirty-three
[...] Read more.
Disruption of fungal cell wall should be an effective intervention strategy. However, the cell wall-disrupting echinocandin drugs, such as caspofungin (CAS), cannot exterminate filamentous fungal pathogens during treatment. For potency improvement of cell wall-disrupting agents (CAS, octyl gallate (OG)), antifungal efficacy of thirty-three cinnamic acid derivatives was investigated against Saccharomyces cerevisiae slt2Δ, bck1Δ, mutants of the mitogen-activated protein kinase (MAPK), and MAPK kinase kinase, respectively, in cell wall integrity system, and glr1Δ, mutant of CAS-responsive glutathione reductase. Cell wall mutants were highly susceptible to four cinnamic acids (4-chloro-α-methyl-, 4-methoxy-, 4-methyl-, 3-methylcinnamic acids), where 4-chloro-α-methyl- and 4-methylcinnamic acids possessed the highest activity. Structure-activity relationship revealed that 4-methylcinnamic acid, the deoxygenated structure of 4-methoxycinnamic acid, overcame tolerance of glr1Δ to 4-methoxycinnamic acid, indicating the significance of para substitution of methyl moiety for effective fungal control. The potential of compounds as chemosensitizers (intervention catalysts) to cell wall disruptants (viz., 4-chloro-α-methyl- or 4-methylcinnamic acids + CAS or OG) was assessed according to Clinical Laboratory Standards Institute M38-A. Synergistic chemosensitization greatly lowers minimum inhibitory concentrations of the co-administered drug/agents. 4-Chloro-α-methylcinnamic acid further overcame fludioxonil tolerance of Aspergillus fumigatus antioxidant MAPK mutants (sakAΔ, mpkCΔ). Collectively, 4-chloro-α-methyl- and 4-methylcinnamic acids possess chemosensitizing capability to augment antifungal efficacy of conventional drug/agents, thus could be developed as target-based (i.e., cell wall disruption) intervention catalysts. Full article
(This article belongs to the Special Issue Small Molecule Catalysts with Therapeutic Potential)
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Open AccessFeature PaperArticle Diallylthiosulfinate (Allicin), a Volatile Antimicrobial from Garlic (Allium sativum), Kills Human Lung Pathogenic Bacteria, Including MDR Strains, as a Vapor
Molecules 2017, 22(10), 1711; doi:10.3390/molecules22101711
Received: 13 September 2017 / Accepted: 9 October 2017 / Published: 12 October 2017
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Abstract
Garlic (Allium sativum) has potent antimicrobial activity due to allicin (diallylthiosulfinate) synthesized by enzyme catalysis in damaged garlic tissues. Allicin gives crushed garlic its characteristic odor and its volatility makes it potentially useful for combating lung infections. Allicin was synthesized (>98%
[...] Read more.
Garlic (Allium sativum) has potent antimicrobial activity due to allicin (diallylthiosulfinate) synthesized by enzyme catalysis in damaged garlic tissues. Allicin gives crushed garlic its characteristic odor and its volatility makes it potentially useful for combating lung infections. Allicin was synthesized (>98% pure) by oxidation of diallyl disulfide by H2O2 using formic acid as a catalyst and the growth inhibitory effect of allicin vapor and allicin in solution to clinical isolates of lung pathogenic bacteria from the genera Pseudomonas, Streptococcus, and Staphylococcus, including multi-drug resistant (MDR) strains, was demonstrated. Minimal inhibitory (MIC) and minimal bactericidal concentrations (MBC) were determined and compared to clinical antibiotics using standard European Committee on Antimicrobial Susceptibility Testing (EUCAST) procedures. The cytotoxicity of allicin to human lung and colon epithelial and murine fibroblast cells was tested in vitro and shown to be ameliorated by glutathione (GSH). Similarly, the sensitivity of rat precision-cut lung slices (PCLS) to allicin was decreased by raising the [GSH] to the approximate blood plasma level of 1 mM. Because allicin inhibited bacterial growth as a vapor, it could be used to combat bacterial lung infections via direct inhalation. Since there are no volatile antibiotics available to treat pulmonary infections, allicin, particularly at sublethal doses in combination with oral antibiotics, could make a valuable addition to currently available treatments. Full article
(This article belongs to the Special Issue Small Molecule Catalysts with Therapeutic Potential)
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