Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
6.7
4.6
Journals
Molecules
Special Issues
Discovery, Characterisation, and Development of Small Molecule Inhibitors
molecules-logo
Submit to Molecules Review for Molecules Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Discovery, Characterisation, and Development of Small Molecule Inhibitors

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

Deadline for manuscript submissions: closed (15 March 2022) | Viewed by 11806

Special Issue Editor

Prof. Dr. Jianguo Fang

E-Mail Website
Guest Editor
School of Chemistry and Chemical Engineering, Nanjing University of Science and Technology (NJUST), Nanjing 210094, China
Interests: redox regulation; reactive oxygen species; thioredoxin; fluorescent probes; anticancer agent
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Small molecule inhibitors play a central role in medicinal chemistry. The treatment of human disease has been dominated by small molecule drugs, and >90% of clinical drugs are small molecules (MW < 1000 D). Small molecule drugs are widely used to treat a variety of human disorders and show great diversity in their action mechanisms. Because of their small size and favorable physiochemical properties, small molecules may penetrate the cell membrane and function as effective enzyme inhibitors or allosteric regulators. Small molecules may also target extracellular proteins or intracellular/membrane receptors. Despite increasing interest in developing biological therapies, such as nucleic-acid-based therapies, cellular and tissue therapies, and antibody-based therapies, small molecules remain the predominant component of an ever-expanding therapeutic toolbox due to their many advantages, e.g., low cost, multiple administration routes, well-defined chemical structures, and lack of immunogenicity.

This Special Issue will focus on the latest developments and discovery in small molecule inhibitors/antagonists of enzymes, transcription factors, receptors, and other macromolecules. Both original research articles and reviews are welcome, from the synthesis/isolation of small molecules and their interactions with potential targets to their cellular or in vivo functions. The development of novel assays for facilitating the discovery of small inhibitors is also encouraged.

Prof. Dr. Jianguo Fang
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 submissions that pass pre-check are 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 semimonthly 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 2700 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

  • small molecule inhibitor
  • antagonist
  • enzyme
  • transcription factor
  • receptor
  • assay development

Published Papers (5 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

10 pages, 2361 KiB  
Article
The Dual Function of PhOH Included in the Coordination Sphere of the Nickel Complexes in the Processes of Oxidation with Dioxygen
by Matienko Ludmila, Zhigacheva Irina, Mil Elena, Albantova Anastasia and Goloshchapov Alexander
Molecules 2022, 27(11), 3502; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27113502 - 30 May 2022
Cited by 1 | Viewed by 1057
Abstract
The role of ligands in the regulation of the catalytic activity of Ni-complexes (Ni(acac)2) in green process-selective ethylbenzene oxidation with O2 into α-phenyl ethyl hydroperoxide is considered in this article. The dual function of phenol (PhOH) included in the coordination [...] Read more.
The role of ligands in the regulation of the catalytic activity of Ni-complexes (Ni(acac)2) in green process-selective ethylbenzene oxidation with O2 into α-phenyl ethyl hydroperoxide is considered in this article. The dual function of phenol (PhOH) included in the coordination sphere of the nickel complex as an antioxidant or catalyst depends on the ligand environment of the metal. The role of intermolecular H-bonds and supramolecular structures (AFM method) in the mechanisms of selective catalysis by nickel complexes in chemical and biological oxidation reactions is analyzed. Full article
(This article belongs to the Special Issue Discovery, Characterisation, and Development of Small Molecule Inhibitors)
►▼ Show Figures

Figure 1

8 pages, 3337 KiB  
Article
Novel Disulfiram Derivatives as ALDH1a1-Selective Inhibitors
by Ziad Omran
Molecules 2022, 27(2), 480; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27020480 - 12 Jan 2022
Cited by 3 | Viewed by 2463
Abstract
Aldehyde dehydrogenase-1a1 (ALDH1a1), the enzyme responsible for the oxidation of retinal into retinoic acid, represents a key therapeutic target for the treatment of debilitating disorders such as cancer, obesity, and inflammation. Drugs that can inhibit ALDH1a1 include disulfiram, an FDA-approved drug to treat [...] Read more.
Aldehyde dehydrogenase-1a1 (ALDH1a1), the enzyme responsible for the oxidation of retinal into retinoic acid, represents a key therapeutic target for the treatment of debilitating disorders such as cancer, obesity, and inflammation. Drugs that can inhibit ALDH1a1 include disulfiram, an FDA-approved drug to treat chronic alcoholism. Disulfiram, by carbamylation of the catalytic cysteines, irreversibly inhibits ALDH1a1 and ALDH2. The latter is the isozyme responsible for important physiological processes such as the second stage of alcohol metabolism. Given the fact that ALDH1a1 has a larger substrate tunnel than that in ALDH2, replacing disulfiram ethyl groups with larger motifs will yield selective ALDH1a1 inhibitors. We report herein the synthesis of new inhibitors of ALDH1a1 where (hetero)aromatic rings were introduced into the structure of disulfiram. Most of the developed compounds retained the anti-ALDH1a1 activity of disulfiram; however, they were completely devoid of inhibitory activity against ALDH2. Full article
(This article belongs to the Special Issue Discovery, Characterisation, and Development of Small Molecule Inhibitors)
►▼ Show Figures

Graphical abstract

14 pages, 1480 KiB  
Article
Synthesis, In Silico Studies, and Evaluation of Syn and Anti Isomers of N-Substituted Indole-3-carbaldehyde Oxime Derivatives as Urease Inhibitors against Helicobacter pylori
by Ishani P. Kalatuwawege, Medha J. Gunaratna and Dinusha N. Udukala
Molecules 2021, 26(21), 6658; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26216658 - 03 Nov 2021
Cited by 5 | Viewed by 2618
Abstract
Gastrointestinal tract infection caused by Helicobacter pylori is a common virulent disease found worldwide, and the infection rate is much higher in developing countries than in developed ones. In the pathogenesis of H. pylori in the gastrointestinal tract, the secretion of the urease [...] Read more.
Gastrointestinal tract infection caused by Helicobacter pylori is a common virulent disease found worldwide, and the infection rate is much higher in developing countries than in developed ones. In the pathogenesis of H. pylori in the gastrointestinal tract, the secretion of the urease enzyme plays a major role. Therefore, inhibition of urease is a better approach against H. pylori infection. In the present study, a series of syn and anti isomers of N-substituted indole-3-carbaldehyde oxime derivatives was synthesized via Schiff base reaction of appropriate carbaldehyde derivatives with hydroxylamine hydrochloride. The in vitro urease inhibitory activities of those derivatives were evaluated against that of Macrotyloma uniflorum urease using the modified Berthelot reaction. Out of the tested compounds, compound 8 (IC50 = 0.0516 ± 0.0035 mM) and compound 9 (IC50 = 0.0345 ± 0.0008 mM) were identified as the derivatives with potent urease inhibitory activity with compared to thiourea (IC50 = 0.2387 ± 0.0048 mM). Additionally, in silico studies for all oxime compounds were performed to investigate the binding interactions with the active site of the urease enzyme compared to thiourea. Furthermore, the drug-likeness of the synthesized oxime compounds was also predicted. Full article
(This article belongs to the Special Issue Discovery, Characterisation, and Development of Small Molecule Inhibitors)
►▼ Show Figures

Graphical abstract

12 pages, 2361 KiB  
Article
2-IPMA Ameliorates PM2.5-Induced Inflammation by Promoting Primary Ciliogenesis in RPE Cells
by Ji Yeon Choi, Ji-Eun Bae, Joon Bum Kim, Doo Sin Jo, Na Yeon Park, Yong Hwan Kim, Ha Jung Lee, Seong Hyun Kim, So Hyun Kim, Hong Bae Jeon, Hye-Won Na, Hyungjung Choi, Hong-Yeoul Ryu, Zae Young Ryoo, Hyun-Shik Lee and Dong-Hyung Cho
Molecules 2021, 26(17), 5409; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26175409 - 06 Sep 2021
Cited by 7 | Viewed by 2777
Abstract
Primary cilia mediate the interactions between cells and external stresses. Thus, dysregulation of primary cilia is implicated in various ciliopathies, e.g., degeneration of the retina caused by dysregulation of the photoreceptor primary cilium. Particulate matter (PM) can cause epithelium injury and endothelial dysfunction [...] Read more.
Primary cilia mediate the interactions between cells and external stresses. Thus, dysregulation of primary cilia is implicated in various ciliopathies, e.g., degeneration of the retina caused by dysregulation of the photoreceptor primary cilium. Particulate matter (PM) can cause epithelium injury and endothelial dysfunction by increasing oxidative stress and inflammatory responses. Previously, we showed that PM disrupts the formation of primary cilia in retinal pigment epithelium (RPE) cells. In the present study, we identified 2-isopropylmalic acid (2-IPMA) as a novel inducer of primary ciliogenesis from a metabolite library screening. Both ciliated cells and primary cilium length were increased in 2-IPMA-treated RPE cells. Notably, 2-IPMA strongly promoted primary ciliogenesis and restored PM2.5-induced dysgenesis of primary cilia in RPE cells. Both excessive reactive oxygen species (ROS) generation and activation of a stress kinase, JNK, by PM2.5 were reduced by 2-IPMA. Moreover, 2-IPMA inhibited proinflammatory cytokine production, i.e., IL-6 and TNF-α, induced by PM2.5 in RPE cells. Taken together, our data suggest that 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in RPE cells. Full article
(This article belongs to the Special Issue Discovery, Characterisation, and Development of Small Molecule Inhibitors)
►▼ Show Figures

Figure 1

19 pages, 3695 KiB  
Article
Enantioenriched Positive Allosteric Modulators Display Distinct Pharmacology at the Dopamine D1 Receptor
by Tim J. Fyfe, Peter J. Scammells, J. Robert Lane and Ben Capuano
Molecules 2021, 26(13), 3799; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26133799 - 22 Jun 2021
Cited by 2 | Viewed by 2057
Abstract
(1) Background: Two first-in-class racemic dopamine D1 receptor (D1R) positive allosteric modulator (PAM) chemotypes (1 and 2) were identified from a high-throughput screen. In particular, due to its selectivity for the D1R and reported lack of [...] Read more.
(1) Background: Two first-in-class racemic dopamine D1 receptor (D1R) positive allosteric modulator (PAM) chemotypes (1 and 2) were identified from a high-throughput screen. In particular, due to its selectivity for the D1R and reported lack of intrinsic activity, compound 2 shows promise as a starting point toward the development of small molecule allosteric modulators to ameliorate the cognitive deficits associated with some neuropsychiatric disease states; (2) Methods: Herein, we describe the enantioenrichment of optical isomers of 2 using chiral auxiliaries derived from (R)- and (S)-3-hydroxy-4,4-dimethyldihydrofuran-2(3H)-one (d- and l-pantolactone, respectively); (3) Results: We confirm both the racemate and enantiomers of 2 are active and selective for the D1R, but that the respective stereoisomers show a significant difference in their affinity and magnitude of positive allosteric cooperativity with dopamine; (4) Conclusions: These data warrant further investigation of asymmetric syntheses of optically pure analogues of 2 for the development of D1R PAMs with superior allosteric properties. Full article
(This article belongs to the Special Issue Discovery, Characterisation, and Development of Small Molecule Inhibitors)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-5
Back to TopTop