Synthesis of Two step Indole Derivatives in a Continuous Flow System

남수민,박찬필 한국공업화학회 2019 한국공업화학회 연구논문 초록집 Vol.2019 No.1

Indole derivatives are used as antibiotics in pharmaceuticals and have various physiological and biological characteristics such as antipyretic, anti-fungal and anti-inflammatory. In this study, the reaction proceeds in two steps. First of all, the first reaction is C3-formylation of indole in the microreactor. As a secondary reaction, the synthesis of Tri(indolyl)methanes(TIM) is carried out by acid catalyst reaction using Indole and Indole-3-carboxyaldehyde synthesized by C3-formylation of Indole. In the case of the first reaction, the microreactor optimized various parameters to obtain 76% yield in 10 minutes. However, the secondary reaction TIM synthesis is difficult to apply to the microreactor because the product is solid. In this study, the problem of solid formation in the Microreactor can be solved by generating product and disperse phase using mineral oil as a carrier phase during synthesis.

Diverse Roles of Microbial Indole Derivatives in Eukaryotic Systems

Bharath Reddy BOYA,Prasun KUMAR,Jintae LEE 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10

Indole and its derivatives are widespread across different life forms, functioning as signalling molecules in prokaryotes and with more diverse roles in eukaryotes. A majority of indoles found in the environment are attributed to bacterial enzymes converting tryptophan into indole and its derivatives. The involvement of indoles among lower organisms as an interspecies and intraspecies signal is well known, with many reports showing that inter-kingdom interactions involving microbial indole compounds are equally important as they influence defence systems and even the behavior of higher organisms. Here, we discuss the role of microbial indoles in eukaryotes and current perspectives in human diseases and, indole derivatives as biomarkers of metabolic state for therapeutic opportunities.

Ecofriendly one-pot biosynthesis of indigo derivative dyes using CYP102G4 and PrnA halogenase

Namgung, Seyun,Park, Hyun A.,Kim, Joonwon,Lee, Pyung-Gang,Kim, Byung-Gee,Yang, Yung-Hun,Choi, Kwon-Young Elsevier 2019 Dyes and pigments Vol.162 No.-

<P><B>Abstract</B></P> <P>In this study, the biosynthesis of various indigoids with novel spectral features and antibacterial activities was investigated. First, 12 indole derivatives as substrates were biotransformed into functional indigoid dyes by <I>E. coli</I> cells expressing CYP102G4 hydroxylase. The indole derivatives included chloro (Cl-), nitro (NO<SUB>2</SUB>-), hydroxy (HO-), methoxy (CH<SUB>3</SUB>O-), methyl (CH<SUB>3</SUB>-), carboxy (COOH-), amino (NH<SUB>3</SUB>-), and cyano (CN-) indoles at the C4 to C7 positions. Interestingly, dramatic color shifts were observed from blue to red, green, purple, and even pink depending on the functional groups and their positions. Next, the biological and physical properties, antibacterial effects, and dying fastness of the prepared compounds were investigated and visually measured. Among the synthesized indigoid dyes, 6,6’-dichloroindigo and 5,5’-dichloroindigo showed the relatively higher cell growth inhibitory activity in the liquid phase. Finally, a one-pot producing strain which produced 7,7’-dichloroindigo from <SMALL>L</SMALL>-tryptophan using tryptophan-7-halogenase (PrnA) and CYP102G4 simultaneously was developed to overcome the disadvantages of uneconomical semi-synthesis through indole precursor feedstocks. The developed producing strain produced approximately 15.4 ± 1.4 mg/L of 7,7’-dichloroindigo in 24 h. To the best of our knowledge, this is the first report of the production of 7,7’-dichloroindigo in <I>E. coli</I> via a one-pot process.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Biological production of eco-friendly indigo derivatives. </LI> <LI> Biotransformation of indole derivatives using CYP102G4. </LI> <LI> One-pot biosynthesis of 7,7’-dichloroindigo by CYP102G4 and PrnA. </LI> <LI> 15.4 mg/L of 7,7’-dichloroindigo production in <I>E. coli</I>. </LI> <LI> Antibacterial activity of indigo derivatives. </LI> </UL> </P>

Exploration of the Binding Mode of Indole Derivatives as Potent HIV-1 Inhibitors Using Molecular Docking Simulations

Balupuri, Anand,Cho, Seung Joo The Basic Science Institute Chosun University 2013 조선자연과학논문집 Vol.6 No.3

The HIV-1 envelope glycoprotein gp120 plays a vital role in the entry of the virus into the host cells. The crucial role of the glycoprotein suggests gp120 as potential drug target for the future antiviral therapies. Identification of the binding mode of small drug like compounds has been an important goal in drug design. In the current study we attempt to propose binding mode of indole derivatives in the binding pocket of gp120. These derivatives are reported to inhibit HIV-1 by acting as attachment inhibitors that bind to gp120 and prevent the gp120-CD4 interaction and thus inhibit the infectivity of HIV-1. To elucidate the molecular basis of the small molecules interactions to inhibit the glycoprotein function we employed the molecular docking simulation approach. This study provides insights to elucidate the binding pattern of indole-based gp120 inhibitors and may help in the rational design of novel HIV-1 inhibitors with improved potency.

Cold-Adapted and Rhizosphere-Competent Strain of Rahnella sp. with Broad-Spectrum Plant Growth-Promotion Potential

( Pratibha Vyas ),( Robin Joshi ),( K. C. Sharma ),( Praveen Rahi ),( Ashu Gulati ),( Arvind Gulati ) 한국미생물 · 생명공학회 2010 Journal of microbiology and biotechnology Vol.20 No.12

A phosphate-solubilizing bacterial strain isolated from Hippophae rhamnoides rhizosphere was identified as Rahnellu sp. based on its phenotypic features and 165 rRNA gene sequence. The bacterial strain showed the growth characteristics of a cold-adapted psychrotroph, with the multiple plant growth-promoting traits of inorganic and organic phosphate solubilization, 1-aminocyclopropane-1-carboxylate-deaminase activity, ammonia generation, and siderophore production. The strain also produced indole-3-acetic acid, indole-3-acetaldehyde, indole-3-acetamide, indole-3-acetonitrile, indole-3-lactic acid, and indole-3-pyruvic acid in tryptophan-supplemented nutrient broth. Gluconic, citric and isocitric acids were the major organic acids detected during tricalcium phosphate solubilization. A rifampicin-resistant mutant of the strain exhibited high rhizosphere competence without disturbance to the resident microbial populations in pea rhizosphere. Seed bacterization with a charcoal-based inoculum significantly increased growth in barley, chickpea, pea, and maize under the controlled environment. Microplot testing of the inoculum at two different locations in pea also showed significant increase in growth and yield. The attributes of cold-tolerance, high rhizosphere competence, and broad-spectrum plant growth-promoting activity exhibited the potential of Rahnella sp. BIHB 783 for increasing agriculture productivity.

Comparison of Some 3-(Substituted-Benzylidene)-1, 3-Dihydro-Indolin Derivatives as Ligands of Tyrosine Kinase Based on Binding Mode Studies and Biological Assay

Olgen, Sureyya The Pharmaceutical Society of Korea 2006 Archives of Pharmacal Research Vol.29 No.11

A series of 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-one, 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-thione and 2, 2'-dithiobis 3-(substituted-benylidene)-1, 3-dihydro-indole derivatives was investigated as inhibitor of $p60^{c-Src}$tyrosine kinase by performing receptor docking studies and inhibitory activity toward tyrosine phosphorylation. Some compounds were shown to be docked at the site, where the selective inhibitor PP1 [1-tert-Butyl-3-p-tolyl-1H-pyrazolo[3,4-d]pyrimidine-4-yl-amine] was embedded at the enzyme active site. Evaluation of all compounds for the interactions with the parameters of lowest binding energy levels, capability of hydrogen bond formations and superimposibility on enzyme active site by docking studies, it can be assumed that 3-(substituted-benzylidene)-1, 3-dihydro-indolin-2-one and thione derivatives have better interaction with enzyme active site then 2, 2'-dithiobis 3-(substituted-benzylidene)-1, 3-dihydro indole derivatives. The test results for the inhibitory activity against tyrosine kinase by Elisa method revealed that 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-thione derivatives have more activity then 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-one derivatives.

Comparison of Some 3-(Substituted-Benzylidene)-1, 3-Dihydro-Indolin Derivatives as Ligands of Tyrosine Kinase Based on Binding Mode Studies and Biological Assay

S?reyya ?lgen 대한약학회 2006 Archives of Pharmacal Research Vol.29 No.11

A series of 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-one, 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-thione and 2, 2’-dithiobis 3-(substituted-benylidene)-1, 3-dihydro-indole derivatives was investigated as inhibitor of p60c-Src tyrosine kinase by performing receptor docking studies and inhibitory activity toward tyrosine phosphorylation. Some compounds were shown to be docked at the site, where the selective inhibitor PP1 [1-tert-Butyl-3-p-tolyl-1Hpyrazolo[ 3,4-d]pyrimidine-4-yl-amine] was embedded at the enzyme active site. Evaluation of all compounds for the interactions with the parameters of lowest binding energy levels, capability of hydrogen bond formations and superimposibility on enzyme active site by docking studies, it can be assumed that 3-(substituted- benzylidene)-1, 3-dihydro-indolin-2-one and thione derivatives have better interaction with enzyme active site then 2, 2’-dithiobis 3-(substitutedbenzylidene)- 1, 3-dihydro indole derivatives. The test results for the inhibitory activity against tyrosine kinase by Elisa method revealed that 3-(substituted-benylidene)-1, 3-dihydro- indolin- 2-thione derivatives have more activity then 3-(substituted-benylidene)-1, 3-dihydro- indolin-2- one derivatives.

One-Pot Synthesis of 3-(Benzo[e]indol-2-yl)-2-oxindoles from Isatin-derived Propargylic Alcohols and N-Acetyl-2-aminonaphthalenes

노화정,서다영,류지연,이준성,김재녕 대한화학회 2017 Bulletin of the Korean Chemical Society Vol.38 No.5

APPLIED MICRPBIAL AND CELL PHYSIOLOGY : Indole and 7-benzyloxyindole attenuate the virulence of Staphylococcus aureus

( Jin Hyung Lee ),( Hyun Seob Cho ),( Younghoon Kim ),( Jung Ae Kim ),( Suhrid Banskota ),( Moo Hwan Cho ),( Jintae Lee ) 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0

Human pathogens can readily develop drug resistance due to the long-term use of antibiotics that mostly inhibit bacterial growth. Unlike antibiotics, antivirulence compounds diminish bacterial virulencewithout affecting cell viability and thus, may not lead to drug resistance. Staphylococcus aureus is a major agent of nosocomial infections and produces diverse virulence factors, such as the yellow carotenoid staphyloxanthin, which promotes resistance to reactive oxygen species (ROS) and the host immune system. To identify novel antivirulence compounds, bacterial signal indole present in animal gut and diverse indole derivatives were investigated with respect to reducing staphyloxanthin production and the hemolytic activity of S. aureus. Treatment with indole or its derivative 7-benzyloxyindole (7BOI) caused S. aureus to become colorless and inhibited its hemolytic ability without affecting bacterial growth. As a result, S. aureus was more easily killed by hydrogen peroxide (H₂O₂) and by human whole blood in the presence of indole or 7BOI. In addition, 7BOI attenuated S. aureus virulence in an in vivo model of nematode Caenorhabditis elegans, which is readily infected and killed by S. aureus. Transcriptional analyses showed that both indole and 7BOI repressed the expressions of severalvirulence genes such as α-hemolysin gene hla, enterotoxin seb, and the protease genes splA and sspA and modulated the expressions of the important regulatory genes agrA and sarA. These findings show that indole derivatives are potential candidates for use in antivirulence strategies against persistent S. aureus infection.

인돌 유도체들의 항산화 작용기전

성도유,박진생,김명정,노재경,양영환,백기주,양융,최진호,이숙희,정해영 대한암예방학회 1999 Journal of cancer prevention Vol.4 No.4