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Novel Functions for Small Molecules
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Novel Functions for Small Molecules

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

Deadline for manuscript submissions: 20 April 2025 | Viewed by 7067

Special Issue Editor

Prof. Dr. Yuh-Lin Wu

E-Mail Website
Guest Editor
Department and Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
Interests: inflammation; cancer; ovary; ghrelin; interleukin-8; cyclooxygenase-2; granulosa cell; growth hormone releasing peptide-2
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Small molecules or micromolecules are low molecular weight (≤1000 daltons) organic compounds that include lipids, monosaccharides, second messengers, other natural products and metabolites, as well as drugs and other xenobiotics. They may be used as research tools to probe biological function as well as leads in the development of new therapeutic options. Virtually all currently used therapeutic agents are small molecules, largely because the development and delivery of small molecule drugs is relatively straightforward; however many challenges remain a significant problem. This Special Issue, “Novel Functions for Small Molecules”, of the International Journal of Molecular Sciences aims to comprise a collection of research or review articles covering the novel functions of any not-yet-sufficiently explored molecules or newly-identified novel functions of well-known molecules by using in vivo or vitro models to address the associated cancer therapy, drug development and so on. The submitted manuscripts are expected to focus on any aspects of cellular, molecular, biochemical, or physiological mechanisms to reveal functional significance of such candidate novel molecules or functions.

Prof. Dr. Yuh-Lin Wu
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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 molecules
  • micromolecules
  • in vivo or vitro models

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Related Special Issue

Published Papers (4 papers)

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Research

17 pages, 6497 KiB  
Article
Structure–Activity Relationship of Oleanane-Type Pentacyclic Triterpenoids on Nuclear Factor κB Activation and Intracellular Trafficking and N-Linked Glycosylation of Intercellular Adhesion Molecule-1
by Kaori Nakano, Yuka Yokota, Quy Van Vu, Francesca Lagravinese and Takao Kataoka
Int. J. Mol. Sci. 2024, 25(11), 6026; https://doi.org/10.3390/ijms25116026 - 30 May 2024
Cited by 1 | Viewed by 615
Abstract
In our previous study, two oleanane-type pentacyclic triterpenoids (oleanolic acid and maslinic acid) were reported to affect the N-glycosylation and intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1). The present study was aimed at investigating the structure–activity relationship of 13 oleanane-type natural triterpenoids [...] Read more.
In our previous study, two oleanane-type pentacyclic triterpenoids (oleanolic acid and maslinic acid) were reported to affect the N-glycosylation and intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1). The present study was aimed at investigating the structure–activity relationship of 13 oleanane-type natural triterpenoids with respect to the nuclear factor κB (NF-κB) signaling pathway and the expression, intracellular trafficking, and N-glycosylation of the ICAM-1 protein in human lung adenocarcinoma A549 cells. Hederagenin, echinocystic acid, erythrodiol, and maslinic acid, which all possess two hydroxyl groups, decreased the viability of A549 cells. Celastrol and pristimerin, both of which possess an α,β-unsaturated carbonyl group, decreased cell viability but more strongly inhibited the interleukin-1α-induced NF-κB signaling pathway. Oleanolic acid, moronic acid, and glycyrrhetinic acid interfered with N-glycosylation without affecting the cell surface expression of the ICAM-1 protein. In contrast, α-boswellic acid and maslinic acid interfered with the N-glycosylation of the ICAM-1 protein, which resulted in the accumulation of high-mannose-type N-glycans. Among the oleanane-type triterpenoids tested, α-boswellic acid and maslinic acid uniquely interfered with the intracellular trafficking and N-glycosylation of glycoproteins. Full article
(This article belongs to the Special Issue Novel Functions for Small Molecules)
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16 pages, 3933 KiB  
Article
Glucosamine Enhancement of Learning and Memory Functions by Promoting Fibroblast Growth Factor 21 Production
by Yu-Ming Chao, Hon-Yen Wu, Sin-Huei Yeh, Ding-I Yang, Lu-Shiun Her and Yuh-Lin Wu
Int. J. Mol. Sci. 2024, 25(8), 4211; https://doi.org/10.3390/ijms25084211 - 10 Apr 2024
Viewed by 1915
Abstract
Fibroblast growth factor 21 (FGF21) plays a crucial role in metabolism and brain function. Glucosamine (GLN) has been recognized for its diverse beneficial effects. This study aimed to elucidate the modulation of FGF21 production by GLN and its impact on learning and memory [...] Read more.
Fibroblast growth factor 21 (FGF21) plays a crucial role in metabolism and brain function. Glucosamine (GLN) has been recognized for its diverse beneficial effects. This study aimed to elucidate the modulation of FGF21 production by GLN and its impact on learning and memory functions. Using both in vivo and in vitro models, we investigated the effects of GLN on mice fed with a normal diet or high-fat diet and on mouse HT22 hippocampal cells, STHdhQ7/Q7 striatal cells, and rat primary cortical neurons challenged with GLN. Our results indicated that GLN promotes learning and memory functions in mice and upregulates FGF21 expression in the hippocampus, cortex, and striatum, as well as in HT22 cells, STHdhQ7/Q7 cells, and cortical neurons. In animals receiving GLN together with an FGF21 receptor FGFR1 inhibitor (PD173074), the GLN-enhanced learning and memory functions and induction of FGF21 production in the hippocampus were significantly attenuated. While exploring the underlying molecular mechanisms, the potential involvement of NF-κB, Akt, p38, JNK, PKA, and PPARα in HT22 and NF-κB, Akt, p38, and PPARα in STHdhQ7/Q7 were noted; GLN was able to mediate the activation of p65, Akt, p38, and CREB in HT22 and p65, Akt, and p38 in STHdhQ7/Q7 cells. Our accumulated findings suggest that GLN may increase learning and memory functions by inducing FGF21 production in the brain. This induction appears to be mediated, at least in part, through GLN’s activation of the NF-κB, Akt, p38, and PKA/CREB pathways. Full article
(This article belongs to the Special Issue Novel Functions for Small Molecules)
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14 pages, 1629 KiB  
Article
Synthesis and Biological Properties of Pyranocoumarin Derivatives as Potent Anti-Inflammatory Agents
by Su Ji Min, Heesu Lee, Myoung-Sook Shin and Jae Wook Lee
Int. J. Mol. Sci. 2023, 24(12), 10026; https://doi.org/10.3390/ijms241210026 - 12 Jun 2023
Cited by 4 | Viewed by 1838
Abstract
This study aimed to synthesize 23 coumarin derivatives and analyze their anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages. A cytotoxicity test performed on LPS-induced RAW264.7 macrophages revealed that none of the 23 coumarin derivatives were cytotoxic. Among the 23 coumarin derivatives, [...] Read more.
This study aimed to synthesize 23 coumarin derivatives and analyze their anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages. A cytotoxicity test performed on LPS-induced RAW264.7 macrophages revealed that none of the 23 coumarin derivatives were cytotoxic. Among the 23 coumarin derivatives, coumarin derivative 2 showed the highest anti-inflammatory activity by significantly reducing nitric oxide production in a concentration-dependent manner. Coumarin derivative 2 inhibited the production of proinflammatory cytokines, including tumor necrosis factor alpha and interleukin-6, and decreased the expression level of each mRNA. In addition, it inhibited the phosphorylation of extracellular signal-regulated kinase, p38, c-Jun NH2-terminal kinase, nuclear factor kappa-B p65 (NF-κB p65), and inducible nitric oxide synthase. These results indicated that coumarin derivative 2 inhibited LPS-induced mitogen-activated protein kinase and NF-κB p65 signal transduction pathways in RAW264.7 cells, as well as proinflammatory cytokines and enzymes related to inflammatory responses, to exert anti-inflammatory effects. Coumarin derivative 2 showed potential for further development as an anti-inflammatory drug for the treatment of acute and chronic inflammatory diseases. Full article
(This article belongs to the Special Issue Novel Functions for Small Molecules)
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13 pages, 3235 KiB  
Article
Design, Synthesis, and Biological Evaluation of 3-Substituted-Indolin-2-One Derivatives as Potent Anti-Inflammatory Agents
by Sung Jin Kim, Sang Hyuk Lee, Heesu Lee, Myoung-Sook Shin and Jae Wook Lee
Int. J. Mol. Sci. 2023, 24(3), 2066; https://doi.org/10.3390/ijms24032066 - 20 Jan 2023
Cited by 1 | Viewed by 1960
Abstract
This study aimed to synthesize and evaluate the anti-inflammatory activity of 3-substituted-indolin-2-one derivatives. Cell viability of 3-substituted-indolin-2-one derivatives was measured with the EZ-Cytox reagent; interleukin (IL)-6, tumor necrosis factor (TNF)-α, and inducible NOS mRNA levels were measured using Taqman qRT-PCR; pro-inflammatory cytokine IL-6 [...] Read more.
This study aimed to synthesize and evaluate the anti-inflammatory activity of 3-substituted-indolin-2-one derivatives. Cell viability of 3-substituted-indolin-2-one derivatives was measured with the EZ-Cytox reagent; interleukin (IL)-6, tumor necrosis factor (TNF)-α, and inducible NOS mRNA levels were measured using Taqman qRT-PCR; pro-inflammatory cytokine IL-6 and TNF-α levels were determined using ELISA kits; the phosphorylation of Akt, JNK, ERK, p38, p65, and IκB protein levels were measured by immunoblotting. Among the nineteen 3-substituted-indolin-2-one derivatives synthesized, 3-(3-hydroxyphenyl)-indolin-2-one showed the highest anti-inflammatory activity, inhibiting the nitric oxide production related to inflammation, suppressing the production of TNF-α and IL-6 in a concentration-dependent manner and mRNA expression. Moreover, 3-(3-hydroxyphenyl)-indolin-2-one significantly inhibited lipopolysaccharide (LPS)-induced signal pathways such as the Akt, MAPK, and NF-κB signaling pathways. Our findings revealed that a 3-substituted-indolin-2-one derivative, 3-(3-hydroxyphenyl)-indolin-2-one, possesses excellent anti-inflammatory activity and can be considered for future research. Full article
(This article belongs to the Special Issue Novel Functions for Small Molecules)
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