Development of S-Methylmethionine Sulfonium Derivatives and Their Skin-Protective Effect against Ultraviolet Exposure

Kim, Won-Serk,Kim, Wang-Kyun,Choi, Nahyun,Suh, Wonhee,Lee, Jinu,Kim, Dae-Duk,Kim, Ikyon,Sung, Jong-Hyuk The Korean Society of Applied Pharmacology 2018 Biomolecules & Therapeutics(구 응용약물학회지) Vol.26 No.3

In a previous study, we have demonstrated that S-methylmethionine sulfonium (SMMS) confers wound-healing and photoprotective effects on the skin, suggesting that SMMS can be used as a cosmetic raw material. However, it has an unpleasant odor. Therefore, in the present study, we synthesized odor-free SMMS derivatives by eliminating dimethyl sulfide, which is the cause of the unpleasant odor and identified two derivatives that exhibited skin-protective effects: one derivative comprised (2S,4S)- and (2R,4S)-2-phenylthiazolidine-4-carboxylic acid and the other comprised (2S,4R)-, (2S,4S)-, (2R,4R)-, and (2R,4S)-2-phenyl-1,3-thiazinane-4-carboxylic acid. We performed in vitro proliferation assays using human dermal fibroblasts (hDFs) and an immortalized human keratinocyte cell line (HaCaT). The two SMMS derivatives were shown to increase hDF and HaCaT cell proliferation as well as improve their survival by protecting against ultraviolet exposure. Moreover, the derivatives regulated the expression of collagen type I and MMP mRNAs against ultraviolet exposure in hDFs, suggesting that these derivatives can be developed as cosmetic raw materials.

Mitochondria-Targeted Vitamin E Protects Skin from UVB-Irradiation

Kim, Won-Serk,Kim, Ikyon,Kim, Wang-Kyun,Choi, Ju-Yeon,Kim, Doo Yeong,Moon, Sung-Guk,Min, Hyung-Keun,Song, Min-Kyu,Sung, Jong-Hyuk The Korean Society of Applied Pharmacology 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.3

Mitochondria-targeted vitamin E (MVE) is designed to accumulate within mitochondria and is applied to decrease mitochondrial oxidative damage. However, the protective effects of MVE in skin cells have not been identified. We investigated the protective effect of MVE against UVB in dermal fibroblasts and immortalized human keratinocyte cell line (HaCaT). In addition, we studied the wound-healing effect of MVE in animal models. We found that MVE increased the proliferation and survival of fibroblasts at low concentration (i.e., nM ranges). In addition, MVE increased collagen production and downregulated matrix metalloproteinase1. MVE also increased the proliferation and survival of HaCaT cells. UVB increased reactive oxygen species (ROS) production in fibroblasts and HaCaT cells, while MVE decreased ROS production at low concentration. In an animal experiment, MVE accelerated wound healing from laser-induced skin damage. These results collectively suggest that low dose MVE protects skin from UVB irradiation. Therefore, MVE can be developed as a cosmetic raw material.

Light-induced electrical switch <i>via</i> photo-responsive nanocomposite film

Lee, Wonsik,Kim, Dongjun,Lim, Joonyoung,Kim, Geonho,Kim, Ikyon,Kim, Songkuk,Kim, Jiwon Elsevier 2018 Sensors and actuators. B Chemical Vol.266 No.-

<P><B>Abstract</B></P> <P>Photo-responsive nanomaterials have attracted a lot of attention since they allow a remote control with a non-invasive stimulus—light. Owing to this property, it has been applied to next-generation electrical devices, which are desired to be flexible and transparent for a wider range of applications. Herein, we developed a flexible, transparent and conductive film which can change its shape <I>via</I> light of specific wavelength to control the electrical conductivity between electrodes. The film is composed of three layers: azobenzene incorporated poly(dimethylsiloxane), AzoPDMS; silk fibroin; and silver nanowires, AgNWs. When azobenzene within the polymer changes its molecular arrangement upon irradiation, the difference in volume changes of AzoPDMS and silk fibroin layer results in the film to bend. Since a silk fibroin layer folds inward upon irradiation, AgNWs are coated onto the silk fibroin layer to be selectively in contact with the electrodes. This photo-responsive nanocomposite film is flexible, transparent and conductive which can be connected to the circuit on demand <I>via</I> light acting as an electrical switch. We believe it can be combined with various transparent electronic devices to further expand its applications.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A flexible, transparent and conductive photo-bending film was fabricated. </LI> <LI> The photo-responsive film consists of photo-responsive/support/conductive layers. </LI> <LI> The film could bend up to 90° with switching time of a few seconds upon irradiation. </LI> <LI> The conductivity of film can be optimized by changing the concentration of silver nanowires. </LI> <LI> The film can be connected to the circuit on demand acting as a light-induced electrical switch. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Development of S-Methylmethionine Sulfonium Derivatives and Their Skin-Protective Effect against Ultraviolet Exposure

( Won-serk Kim ),( Wang-kyun Kim ),( Nahyun Choi ),( Wonhee Suh ),( Jinu Lee ),( Dae-duk Kim ),( Ikyon Kim ),( Jong-hyuk Sung ) 한국응용약물학회 2018 Biomolecules & Therapeutics(구 응용약물학회지) Vol.26 No.3

In a previous study, we have demonstrated that S-methylmethionine sulfonium (SMMS) confers wound-healing and photoprotective effects on the skin, suggesting that SMMS can be used as a cosmetic raw material. However, it has an unpleasant odor. Therefore, in the present study, we synthesized odor-free SMMS derivatives by eliminating dimethyl sulfide, which is the cause of the unpleasant odor and identified two derivatives that exhibited skin-protective effects: one derivative comprised (2S,4S)- and (2R,4S)-2-phenylthiazolidine-4-carboxylic acid and the other comprised (2S,4R)-, (2S,4S)-, (2R,4R)-, and (2R,4S)-2-phenyl-1,3- thiazinane-4-carboxylic acid. We performed in vitro proliferation assays using human dermal fibroblasts (hDFs) and an immortalized human keratinocyte cell line (HaCaT). The two SMMS derivatives were shown to increase hDF and HaCaT cell proliferation as well as improve their survival by protecting against ultraviolet exposure. Moreover, the derivatives regulated the expression of collagen type I and MMP mRNAs against ultraviolet exposure in hDFs, suggesting that these derivatives can be developed as cosmetic raw materials.

Mitochondria-Targeted Vitamin E Protects Skin from UVB-Irradiation

( Won Serk Kim ),( Ikyon Kim ),( Wang Kyun Kim ),( Ju Yeon Choi ),( Doo Yeong Kim ),( Sung Guk Moon ),( Hyung Keun Min ),( Min Kyu Song ),( Jong Hyuk Sung ) 한국응용약물학회 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.3

Mitochondria-targeted vitamin E (MVE) is designed to accumulate within mitochondria and is applied to decrease mitochondrial oxidative damage. However, the protective effects of MVE in skin cells have not been identified. We investigated the protective effect of MVE against UVB in dermal fibroblasts and immortalized human keratinocyte cell line (HaCaT). In addition, we studied the wound-healing effect of MVE in animal models. We found that MVE increased the proliferation and survival of fibroblasts at low concentration (i.e., nM ranges). In addition, MVE increased collagen production and downregulated matrix metalloproteinase1. MVE also increased the proliferation and survival of HaCaT cells. UVB increased reactive oxygen species (ROS) production in fibroblasts and HaCaT cells, while MVE decreased ROS production at low concentration. In an animal experiment, MVE accelerated wound healing from laser-induced skin damage. These results collectively suggest that low dose MVE protects skin from UVB irradiation. Therefore, MVE can be developed as a cosmetic raw material.

Diversity-Oriented Construction of Highly Substituted Indolizinones

Kim, Kyungsun,Kim, Ikyon American Chemical Society 2010 Journal of combinatorial chemistry Vol.12 No.3

<P>Rapid generation of a small library of highly functionalized indolizonones was realized by exploiting three palladium-catalyzed cross-coupling reactions of 2-iodoindolizinones which in turn were readily accessed via sequential iodine-mediated cyclization/1,2-shift reactions of propargylic alcohols.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jcchff/2010/jcchff.2010.12.issue-3/cc100015k/production/images/medium/cc-2010-00015k_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/cc100015k'>ACS Electronic Supporting Info</A></P>

Domino Knoevenagel Condensation/Intramolecular Aldol Cyclization Route to Diverse Indolizines with Densely Functionalized Pyridine Units

Kim, Myungock,Jung, Youngeun,Kim, Ikyon American Chemical Society 2013 Journal of organic chemistry Vol.78 No.20

<P>A highly efficient [4 + 2] annulation route to polysubstituted indolizines is described employing a domino Knoevenagel condensation/intramolecular aldol cyclization process as a key step. Construction of pyridine rings in indolizine skeleton was rapidly achieved from several pyrrole-2-carboxaldehydes in good to excellent yields, leading to indolizines with various substituents at the 5, 6, and 7 positions depending on the reacting active methylene partners.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/joceah/2013/joceah.2013.78.issue-20/jo401801j/production/images/medium/jo-2013-01801j_0009.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jo401801j'>ACS Electronic Supporting Info</A></P>

The Photoprotective Effect of <i>S</i> -Methylmethionine Sulfonium in Skin

Kim, Won-Serk,Seo, Hyun-Min,Kim, Wang-Kyun,Choi, Joon-Seok,Kim, Ikyon,Sung, Jong-Hyuk MDPI 2015 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.16 No.8

<P><I>S</I>-Methylmethionine sulfonium (SMMS) was reported to have wound-healing effects; we therefore have investigated the photoprotective effect of SMMS in the present study. SMMS increased the viability of keratinocyte progenitor cells (KPCs) and human dermal fibroblasts (hDFs) following ultraviolet B (UVB) irradiation, and reduced the UVB-induced apoptosis in these cells. SMMS increased the phosphorylation of extracellular signal-regulated kinases (ERK), and the inhibitor of the mitogen-activated protein kinase pathway significantly decreased the SMMS-induced viability of KPCs and hDFs. In addition, SMMS attenuated the UVB-induced reactive oxygen species (ROS) generation in KPCs and hDFs. SMMS induced the collagen synthesis and reduced the matrix metalloproteinase-1 expression in UVB-irradiated hDFs. In animal studies, application of 5% and 10% SMMS before and after UVB-irradiation significantly decreased the UVB-induced erythema index and depletion of Langerhans cells. In summary, SMMS protects KPCs and hDFs from UVB irradiation, and reduces UVB-induced skin erythema and immune suppression. Therefore, SMMS can be used as a cosmetic raw material, and protect skin from UVB.</P>

Design, synthesis, and biological evaluation of novel pyrrolo[1,2-<i>a</i>]pyrazine derivatives

Kim, Jinwoo,Park, Mikyung,Choi, Jiwon,Singh, Dileep Kumar,Kwon, Ho Jeong,Kim, Seong Hwan,Kim, Ikyon Elsevier 2019 Bioorganic & medicinal chemistry letters Vol.29 No.11

<P><B>Abstract</B></P> <P>A pyrrolo[1,2-<I>a</I>]pyrazine-based chemical territory was expanded via construction of new chemical library with distinctive substitution patterns, which was made possible by regiodivergent electrophilic acylation followed by aldol condensation. Biological screening of the compounds in this class revealed that the viability of human lymphoma U937 cells was strongly inhibited by <B>6b</B> with a methoxy group at the <I>o</I>-position of the aromatic ring, but not by compounds <B>6t-w</B> bearing a halogen at the <I>o</I>-position. Furthermore, <B>6x</B> having a 2,4-dimethoxyphenyl group inhibited the survival of U937 cells more potently than <B>6b</B>. In contrast, <B>6y</B> possessing a 2,5-dimethoxyphenyl moiety did not show effective inhibition, implying the importance of orientation of the substituent(s) around the benzene ring. The anticancer action of <B>6x</B> with safe therapeutic window could be associated with the FTase-p38 signaling axis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> New pyrrolo[1,2-<I>a</I>]pyrazine-based chemical space via regiodivergent acetylation/formylation followed by aldol condensation. </LI> <LI> Installation of a chalcone unit around the basic pyrrolo[1,2-<I>a</I>]pyrazine in a different orientation. </LI> <LI> Anticancer screening of the synthesized pyrrolo[1,2-<I>a</I>]pyrazine-chalcone hybrids. </LI> <LI> Identification of structural requirement of pyrrolo[1,2-<I>a</I>]pyrazine-chalcone skeleton to inhibit human lymphoma U937 cells. </LI> <LI> Anticancer activity of <B>6x</B> via the caspase-dependent apoptosis. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Direct Access to Various 1-Substituted-imidazo[1,5-a]pyridine-3(2H)-thione Derivatives

Ikyon Kim*,Ge Hyeoung Lee,Zae Sung No 대한화학회 2007 Bulletin of the Korean Chemical Society Vol.28 No.4