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.

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.

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>

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>

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.

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.

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

Biological evaluation of indolizine-chalcone hybrids as new anticancer agents

Park, Sujin,Kim, Eun Hye,Kim, Jinwoo,Kim, Seong Hwan,Kim, Ikyon Elsevier 2018 European journal of medicinal chemistry Vol.144 No.-

<P><B>Abstract</B></P> <P>A new chemical space was explored based on an indolizine-chalcone hybrid, which was readily accessible by base-mediated aldol condensation of indolizine bearing a 7-acetyl group with various (hetero)aromatic aldehydes. Their anticancer effect was evaluated, revealing that indolizine-chalcone hybrids with 3,5-dimethoxyphenyl group (<B>4h</B>) or the halogen at the meta position (<B>4j</B> and <B>4l</B>) could have the potential to induce the caspase-dependent apoptosis of human lymphoma cells.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A new chemical space with an indolizine-chalcone hybrid skeleton was designed and synthesized. </LI> <LI> Various indolizine-chalcone derivatives were constructed in a divergent manner. </LI> <LI> Anticancer activity of this scaffold was investigated. </LI> <LI> Some of these analogues was found to induce the caspase-dependent apoptosis of human lymphoma cells. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Synthesis and biological evaluation of novel Ani9 derivatives as potent and selective ANO1 inhibitors

Seo, Yohan,Kim, Jinhwang,Chang, Jiwon,Kim, Seong Soon,Namkung, Wan,Kim, Ikyon Elsevier 2018 European journal of medicinal chemistry Vol.160 No.-

<P><B>Abstract</B></P> <P>Anoctamin 1 (ANO1), a calcium-activated chloride channel, is highly expressed and amplified in a number of carcinomas including breast, pancreatic and prostate cancers. Downregulation of ANO1 expression and function significantly inhibits cell proliferation, migration, and invasion of various cancer cell lines. Development of potent and selective ANO1 inhibitors is currently desirable, which may provide a new strategy for cancer treatment. Our previous study revealed a new class of ANO1 inhibitor, (<I>E</I>)-2-(4-chloro-2-methylphenoxy)-<I>N'</I>-(2-methoxybenzylidene)acetohydrazide (Ani9) and structural optimization via chemical modification of Ani9 basic skeleton was undertaken for the development of more potent and specific inhibitors of ANO1. Structure-activity relationship studies with newly synthesized derivatives revealed a number of potent ANO1 inhibitors, among which <B>5f</B> is the most potent inhibitor with an IC<SUB>50</SUB> value of 22 nM. The selectivity analyses showed that <B>5f</B> has excellent selectivity to ANO1 (>1000-fold over ANO2). In cellular assays, <B>5f</B> significantly inhibited cell proliferation of PC3, MCF7, and BxPC3 cells expressing high levels of ANO1. In addition, <B>5f</B> strongly reduced the protein levels of ANO1 in PC3 cells. This study will be useful in the development of ANO1 inhibitors for treatment of cancer and other ANO1-related diseases.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Chemical derivatives of Ani9, an ANO1 inhibitor, were designed and synthesized in order to identify more potent and selective ANO1 inhibitors. </LI> <LI> Structure-activity relationship studies with new derivatives revealed <B>5f</B>, the most potent ANO1 inhibitor with an IC<SUB>50</SUB> value of 22 nM. </LI> <LI> The selectivity analyses revealed that <B>5f</B> has an excellent selectivity to ANO1 (>1000-fold over ANO2). </LI> <LI> <B>5f</B> significantly inhibited cell viability of PC3, MCF7 and BxPC3 cells expressing high levels of ANO1 and reduced protein stability of ANO1. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>