Article
Biochemistry & Molecular Biology
Shekh Sabir, Theerthankar Das, Rajesh Kuppusamy, Tsz Tin Yu, Mark D. P. Willcox, David StC Black, Naresh Kumar
Summary: In this study, a series of novel quinazolinone disulfide-containing competitive inhibitors of PqsR were designed and synthesized. The most potent analogue, 8q, effectively inhibited the pqs system, leading to suppression of pyocyanin production and reduction in biofilm formation by P. aeruginosa. The compound also showed synergy when used in combination with known antibiotics.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Osvaldo S. Ascenso, Gonzalo Carrau, Karina B. Xavier, M. Rita Ventura, Christopher D. Maycock
Summary: A new synthetic route for the quorum sensing signal Autoinducer-2 (AI-2) was described, using [1-C-13]-bromoacetic acid as starting material to prepare [4-C-13]-AI-2. The key step in this process involved an enantioselective reduction of an intermediate ketone, providing both enantiomers of the labeled or unlabeled parent compound for an improved synthesis of [1-C-13]-AI-2.
Review
Pharmacology & Pharmacy
Alessandro Polizzi, Martina Donzella, Giada Nicolosi, Simona Santonocito, Paolo Pesce, Gaetano Isola
Summary: Chemical molecules are used by microorganisms for communication through quorum sensing. Inhibiting quorum sensing can disrupt oral biofilm formation and reduce the impact of periodontitis. The use of antibiotics and antiseptics carries risks, while quorum sensing inhibitors have potential as a solution for treating periodontitis.
Article
Infectious Diseases
Sahil Shandil, Tsz Tin Yu, Shekh Sabir, David StC. Black, Naresh Kumar
Summary: As bacteria develop resistance against antimicrobials, alternative methods to tackle this issue must be developed. In this study, quinazolinone inhibitors were designed using molecular docking to target the pqs system in P. aeruginosa. Compound 6b showed the highest pqs inhibitory activity and no bacterial growth inhibition.
Article
Microbiology
Xiangyong Zeng, Yunman Zou, Jia Zheng, Shuyi Qiu, Lanlan Liu, Chaoyang Wei
Summary: This review focuses on the microbial community from the perspective of quorum sensing, which plays important roles in substance cycles, product synthesis, and species evolution. It provides a theoretical basis for controlling the microbial community using quorum sensing approaches and summarizes the latest progress in applications of quorum sensing in wastewater treatment, human health, food fermentation, and synthetic biology. The relationships between quorum sensing and microbial interactions are also explored in depth.
MICROBIOLOGICAL RESEARCH
(2023)
Article
Chemistry, Medicinal
Yijie Xu, Chunlan Zeng, Huiqi Wen, Qianqian Shi, Xu Zhao, Qingbin Meng, Xingzhou Li, Junhai Xiao
Summary: Several AI-2 QSIs targeting the LsrK/HPr PPI site have been discovered, providing potential for finding more effective AI-2 QSIs.
Article
Chemistry, Multidisciplinary
Qianqian Shi, Huiqi Wen, Yijie Xu, Xu Zhao, Jing Zhang, Ye Li, Qingbin Meng, Fang Yu, Junhai Xiao, Xingzhou Li
Summary: This study focused on the role of LsrK and its potential as a target for Quorum Sensing Inhibitors (QSIs). Through various methods including molecular dynamics simulation, virtual screening, and laboratory assays, several potential LsrK kinase inhibitors were identified. Four compounds were found to effectively inhibit LsrK activity, and two of them were confirmed to specifically bind to LsrK. This research provides valuable insights for the discovery of QSIs that can avoid the emergence of drug resistance.
FRONTIERS IN CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Aditi Vashistha, Nikhil Sharma, Yerramsetti Nanaji, Deepak Kumar, Gurpal Singh, Ravi P. Barnwal, Ashok Kumar Yadav
Summary: The overuse and inappropriate use of antibiotics has led to the development of drug resistant bacterial strains. Biofilm, a complex microorganism aggregation, plays a crucial role in infectious diseases. Efforts to disrupt biofilms have identified molecules that can inhibit quorum sensing, offering potential treatments for bacterial infections with lower dosages of medications.
BIOORGANIC CHEMISTRY
(2023)
Review
Microbiology
Ronit Vogt Sionov, Doron Steinberg
Summary: Biofilm formation plays a crucial role in chronic and recurrent bacterial infections, protecting the embedded bacteria from antibiotics and making treatment difficult. Quorum sensing and efflux pump systems are important factors in biofilm formation and antibiotic resistance. Targeting these regulatory elements could be a promising approach to combat antibiotic-resistant biofilm-related bacterial infections.
Article
Immunology
Giulia Giallonardi, Morgana Letizia, Marta Mellini, Emanuela Frangipani, Nigel Halliday, Stephan Heeb, Miguel Camara, Paolo Visca, Francesco Imperi, Livia Leoni, Paul Williams, Giordano Rampioni
Summary: Pseudomonas aeruginosa is a model pathogen with multiple quorum sensing circuits that control virulence factor production and biofilm formation. The pqs QS system in P. aeruginosa synthesizes AQs including HHQ and PQS, which act as signal molecules. Transcriptomic analyses show that HHQ and PQS influence gene expression through PqsR-dependent and -independent pathways. However, HQNO has no effect on P. aeruginosa transcriptome. Mutation of pqsL in P. aeruginosa leads to autolysis in colony biofilms through the accumulation of HHQ and activation of Pf4 prophage.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Review
Chemistry, Medicinal
Maxwell Ampomah-Wireko, Chunying Luo, Yaquan Cao, Huanhuan Wang, Lauraine Nininahazwe, Chunli Wu
Summary: Pathogenic bacteria utilize quorum sensing (QS) to control cellular functions based on population density, making it a potential target for new drug development. Inhibiting the QS mechanism could be an effective strategy to combat infections and drug resistance. Current research focuses on understanding the quorum-sensing network systems and developing novel anti-QS inhibitors in Gram-negative bacteria.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Immunology
Sathursha Gunaratnam, Mathieu Millette, Lynne McFarland, Herbert L. DuPont, Monique Lacroix
Summary: This paper discusses the potential of opportunistic pathogenic bacteria to cause disease when disrupting the normal microbiome, and current therapeutic strategies for Clostridioides difficile, including disrupting virulence factor production through interfering with quorum sensing systems. Probiotics and other QS inhibitors targeting QS systems may represent important new directions for the treatment and prevention of C. difficile infections.
MICROBIAL PATHOGENESIS
(2021)
Article
Microbiology
Yosra A. Helmy, Dipak Kathayat, Loic Deblais, Vishal Srivastava, Gary Closs, Robert J. Tokarski, Oluwatosin Ayinde, James R. Fuchs, Gireesh Rajashekara
Summary: Avian pathogenic Escherichia coli (APEC), a zoonotic pathogen with public health importance, causes severe economic losses to the poultry industry. In this study, a novel quorum sensing autoinducer-2 inhibitor, Q9-5, showed higher anti-APEC efficacy in chickens compared to the currently used antibiotic. QSI-5 also increased the chicken's body weight gain and did not impact the cecal microbiota composition. Overall, QSI-5 represents a promising lead compound for developing novel anti-virulence therapies for APEC infections in chickens and other associated infections in humans.
MICROBIOLOGY SPECTRUM
(2022)
Review
Microbiology
Veronica Lazar, Alina Maria Holban, Carmen Curutiu, Mariana Carmen Chifiriuc
Summary: Pathogenic bacteria have the ability to adapt to their environment and develop biofilms, increasing their resistance to stress factors such as antibiotics. Targeting quorum sensing and biofilm formation is a promising approach for discovering novel antibiofilm strategies.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Environmental Sciences
Wen-Qian Wang, Xiao-Chi Feng, Hong-Tao Shi, Yong-Mei Wang, Chen-Yi Jiang, Zi-Jie Xiao, Yu-Jie Xu, Xin Zhang, Yuan Yuan, Nan-Qi Ren
Summary: This study found that three phytochemicals can inhibit biofilm formation in Pseudomonas aeruginosa by obstructing the transmembrane transport of quorum sensing (QS) signals. The inhibitors affected the structure and composition of biofilms, suppressed bacterial motility and QS-related virulence factors, and decreased the extracellular concentration of QS signaling molecules. This study provides new insights and strategies for biofilm contamination control.
ENVIRONMENTAL RESEARCH
(2023)
Article
Chemistry, Organic
Toshiki Yamashiro, Takumi Abe, Daisuke Sawada
Summary: A formal cine-substitution/hydrolysis of 3-azidoindoles generated from 3-azido-2-methoxyindolines (AZINs) is reported. This protocol allows for the introduction of various carboxylic acids and alcohols into indolin-3-ones at the C2-position, producing 2-monoacyloxy or alkoxy indolin-3-ones.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Multidisciplinary
Takumi Abe, Toshiki Yamashiro, Kaho Shimizu, Daisuke Sawada
Summary: This work reports the novel reactivity of hemiaminal as a precursor for multi-site indole editing. The HFIP-promoted indole editing of indoline hemiaminals produces 2-arylindoles through a ring-switch sequence. The key to the success of this transformation is the use of a cyclic hemiaminal as an alpha-amino aldehyde surrogate under transient tautomeric control. This transformation exhibits mild reaction conditions and high yields with broad functional group tolerance.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Organic
Miho Ibara, Takumi Abe, Daisuke Sawada
Summary: This article presents an important reaction in peptide synthesis, which distinguishes the terminal amino group and selectively transforms only the N-terminal protecting group. Furthermore, this strategy is applicable to the late stage of peptide synthesis and allows for the introduction of fluorine into peptides.
Article
Plant Sciences
Takumi Abe, Ren Nakajima, Toshiki Yamashiro, Daisuke Sawada
Summary: In this study, Echinosulfonic acid D, a sponge metabolite with recently reassigned structure, was synthesized for the first time. The key step involved the double indolization of dimethylbarbituric acid using the umpolung indole reagent, followed by a hydrolysis/ decarboxylation/esterification sequence.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Chemistry, Organic
Motohiro Yasui, Haruna Ohbu, Maho Ishikawa, Tatsuhito Yoshida, Norihiko Takeda, Seiya Hirao, Takumi Abe, Masafumi Ueda
Summary: Spiro[indole-3,3'-pyrrolidine]-2'-ones were synthesized via one-pot chloroformylation-dearomatizing spirocyclization of tryptamine derivatives. Additionally, the thio equivalent spiro[indole-3,3'-pyrrolidine]-2'-thiones, which were previously unreported, were synthesized. The procedures are easily implemented, have a broad scope, and are transition-metal-free and cheap. To demonstrate the utility of the synthetic methodology, the spiro[indole-3,3'-pyrrolidine]-2'-ones were converted into heterocyclic scaffolds, such as an optically active spiroindoline and spirooxindole.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Shihui Liu, Toshihiko Matsuo, Takumi Abe
Summary: NK-4 plays a key role in the treatment of various diseases, such as allergies, bacterial infections, wound healing, antiviral effects, and peripheral nerve disease. It is currently approved for use in Japan for treating allergies, loss of appetite, sleepiness, anemia, peripheral neuropathy, suppurative diseases, wounds, heat injuries, frostbite, and tinea pedis. The pharmacological effects of NK-4 are being explored for the treatment of more diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Organic
Toshiki Yamashiro, Keisuke Tokushige, Takumi Abe
Summary: The paper presents an unprecedented method for synthesizing indolines with an N3-quinazolin-2,4-dione moiety using an AZIN. The concise synthesis involves a tandem Staudinger/chemo-selective azaWittig/cyclization sequence of AZINs with isatoic anhydride by a one pot protocol.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Keisuke Tokushige, Toshiki Yamashiro, Seiya Hirao, Takumi Abe
Summary: In this study, a C3-N1' cross-coupling reaction of indoles was achieved using N-methoxyindoles as N-electrophilic indole reagents in the presence of a Lewis acid. The generated bisindoles served as latent C3-nucleophiles, allowing for their use as strategic intermediates in sequential C3-N1'-C3'-N1'' triindole formations. The potential synthetic usefulness of this sequential transformation was demonstrated in the construction of C3-N1 looped polyindoles.
CHEMISTRY-SWITZERLAND
(2023)
Article
Chemistry, Organic
Kazuma Sugitate, Toshiki Yamashiro, Ibuki Takahashi, Koji Yamada, Takumi Abe
Summary: The structures of oxytrofalcatins B and C have been revised as oxazoles instead of benzoyl indole core through synthesis and NMR comparison. The synthetic route developed in this study contributes to a better understanding of the biosynthetic pathways for natural 2,5-diaryloxazoles.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Toshiki Yamashiro, Takumi Abe, Masaru Tanioka, Shinichiro Kamino, Daisuke Sawada
Summary: The use of 3-azidoindoles in organic synthesis is challenging due to their instabilities. However, a new approach using 3-azidoindole surrogates has been developed, which are bench-stable and undergo capturing in situ to afford 3-substitued indoles through formal ipso-substitution of the azide group by nucleophiles. Furthermore, the fleeting 3-azidoindoles show a C3-electrophilic character for the first time.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Takumi Abe, Kenta Noda, Daisuke Sawada
Summary: In this study, readily available ammonium hemiaminals and commercially available acetonitriles were introduced as new precursors for a one-pot synthesis of alpha-substituted indolylacetamides. The method demonstrated broad substrate scope, good functional group tolerance, and the ability for gram-scale synthesis. Mechanistic experiments revealed that the cyano group is trapped by a hydroxy group of hemiaminals under metal-free conditions en route to the desired primary amides.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Takumi Abe, Seiya Hirao, Toshiki Yamashiro
CHEMICAL COMMUNICATIONS
(2020)
Review
Chemistry, Organic
Takumi Abe, Koji Yamada, Takahide Nishi
JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN
(2020)
Article
Chemistry, Organic
Takumi Abe, Seiya Hirao
ORGANIC & BIOMOLECULAR CHEMISTRY
(2020)
Article
Chemistry, Multidisciplinary
Seiya Hirao, Toshiki Yamashiro, Kyouka Kohira, Naoki Mishima, Takumi Abe
CHEMICAL COMMUNICATIONS
(2020)