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Special Issue "Novel Functions for Small Molecules"

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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
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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

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Research

Open AccessArticle

Synthesis and Biological Properties of Pyranocoumarin Derivatives as Potent Anti-Inflammatory Agents

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Int. J. Mol. Sci. 2023, 24(12), 10026; https://doi.org/10.3390/ijms241210026 - 12 Jun 2023

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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, 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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Open AccessArticle

Design, Synthesis, and Biological Evaluation of 3-Substituted-Indolin-2-One Derivatives as Potent Anti-Inflammatory Agents

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Int. J. Mol. Sci. 2023, 24(3), 2066; https://doi.org/10.3390/ijms24032066 - 20 Jan 2023

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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 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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