Article
Chemistry, Applied
Debora Feitosa Muniz, Cristina Rodrigues dos Santos Barbosa, Irwin Rose Alencar de Menezes, Erlanio Oliveira de Sousa, Raimundo Luiz Silva Pereira, Joao Tavares Calixto Junior, Pedro Silvino Pereira, Yedda M. L. S. de Matos, Roger H. S. da Costa, Cicera Datiane de Morais Oliveira-Tintino, Henrique Douglas Melo Coutinho, Jose Maria Barbosa Filho, Gabriela Ribeiro de Sousa, Jaime Ribeiro Filho, Jose Pinto Siqueira-Junior, Saulo Relison Tintino
Summary: This study evaluated the antibacterial activity of eugenol and its derivatives against Staphylococcus aureus NorA efflux pump, showing synergistic effects with some compounds. The findings suggest the potential use of eugenol derivatives in antibacterial drug development, particularly in strains carrying the NorA pump.
Article
Microbiology
Nishtha Chandal, Rushikesh Tambat, Ritu Kalia, Gautam Kumar, Nisha Mahey, Sanjay Jachak, Hemraj Nandanwar
Summary: In this study, a chemically synthesized indole derivative, SMJ-5, was found to be a potent NorA efflux pump inhibitor in Staphylococcus aureus. It increased the accumulation of ethidium bromide and norfloxacin, eradicated biofilm, and prolong the post-antibiotic effect when combined with ciprofloxacin. SMJ-5 also inhibited the staphyloxanthin virulence and showed enhanced bactericidal activity against S. aureus. Additionally, SMJ-5 indirectly inhibited the NorA efflux pump at the transcriptional level.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Nishtha Chandal, Rushikesh Tambat, Ritu Kalia, Gautam Kumar, Nisha Mahey, Sanjay Jachak, Hemraj Nandanwar
Summary: In this study, chemically synthesized indole derivatives were screened and a potent NorA efflux pump inhibitor, SMJ-5, was identified. The combination of SMJ-5 and ciprofloxacin showed enhanced bactericidal activity against S. aureus, and could eradicate S. aureus biofilm and prolong the post-antibiotic effect. SMJ-5 also inhibited staphyloxanthin virulence and NorA efflux pump at the transcriptional level indirectly.
MICROBIOLOGY SPECTRUM
(2023)
Article
Chemistry, Medicinal
Tommaso Felicetti, Nicholas Cedraro, Andrea Astolfi, Giada Cernicchi, Gianmarco Mangiaterra, Salvatore Vaiasicca, Serena Massari, Giuseppe Manfroni, Maria Letizia Barreca, Oriana Tabarrini, Francesca Biavasco, Violetta Cecchetti, Carla Vignaroli, Stefano Sabatini
Summary: Antimicrobial resistance (AMR) is a serious global health issue. Efflux pumps play a significant role in the development of resistance and biofilm formation. The search for non-antibiotic molecules that can block efflux pumps is a promising strategy. This study reports a new series of potent derivatives that block efflux pumps and demonstrate synergy with ciprofloxacin against resistant strains of Staphylococcus aureus.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Infectious Diseases
Elisa Rampacci, Tommaso Felicetti, Giada Cernicchi, Valentina Stefanetti, Stefano Sabatini, Fabrizio Passamonti
Summary: One approach to treating antibiotic-resistant bacteria is to co-administer efflux pump inhibitors (EPIs) with antibiotics to break resistances connected with antibacterial efflux. In this study, ten compounds were evaluated for their ability to inhibit efflux and synergize with different antibiotics in Staphylococcus pseudintermedius. Hit compounds 1, 6, and 8 were considered the best EPIs for S. pseudintermedius. These findings provide valuable data for further optimization and development of EPIs for treating staphylococcal infections.
Article
Biotechnology & Applied Microbiology
Nisha Mahey, Rushikesh Tambat, Dipesh Kumar Verma, Nishtha Chandal, Krishan Gopal Thakur, Hemraj Nandanwar
Summary: In this study, the researchers identified five azoles as potential efflux pump inhibitors (EPIs) for Staphylococcus aureus, demonstrating synergistic effects with tetracycline against the bacterium and reducing biofilm formation significantly at clinically relevant concentrations. This suggests that repurposing approved drugs like azoles could be a promising strategy for combating antimicrobial resistance and reducing biofilm formation in clinical settings.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2021)
Article
Microbiology
Nisha Mahey, Rushikesh Tambat, Nishtha Chandal, Dipesh Kumar Verma, Krishan Gopal Thakur, Hemraj Nandanwar
Summary: This study identified six clinically approved drugs that can inhibit the NorA efflux pump, showing synergism with fluoroquinolones and reducing antibiotic resistance in Staphylococcus aureus. These drugs also displayed anti-biofilm properties and efficacy in treating severe S. aureus infections in animal models.
MICROBIOLOGY SPECTRUM
(2021)
Article
Biochemistry & Molecular Biology
Gautam Kumar, Asha Kiran Tudu
Summary: Staphylococcus aureus (S. aureus) is a pathogen responsible for various infections with life-threatening complications. The misuse of antibiotics has led to the emergence of multidrug-resistant pathogens. Bacteria have developed mechanisms to avoid the effects of antibiotics. Inhibitors of multidrug efflux pumps are considered alternative therapeutic options. Natural products and their derived compounds can serve as NorA efflux pump inhibitors.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Bhawandeep Kaur, Jeena Gupta, Sarika Sharma, Divakar Sharma, Sandeep Sharma
Summary: Staphylococcus aureus is a common pathogen causing various infections, with Methicillin-Resistant Staphylococcus aureus (MRSA) being particularly concerning. The primary antimicrobial resistance mechanisms in S. aureus involve efflux pumps and biofilm formation, with quorum sensing and drug efflux playing crucial roles. Efflux pump inhibitors (EPIs) have been identified as a promising approach to combat bacterial resistance, by inhibiting drug efflux mechanisms and transport of quorum sensing signalling molecules.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Medicine, Research & Experimental
Janaina Esmeraldo Rocha, Thiago Sampaio de Freitas, Jayze da Cunha Xavier, Raimundo Luiz Silva Pereira, Francisco Nascimento Pereira Junior, Carlos Emidio Sampaio Nogueira, Marcia Machado Marinho, Paulo Nogueira Bandeira, Mateus Rodrigues de Oliveira, Emmanuel Silva Marinho, Alexandre Magno Rodrigues Teixeira, Helcio Silva dos Santos, Henrique Douglas Melo Coutinho
Summary: A large number of infections worldwide are caused by multi-resistant bacteria, resulting in approximately 700,000 deaths per year. Chalcones, a class of compounds known for their broad biological activities, including antimicrobial and anticancer properties, are being studied for their potential to combat microbial drug resistance.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Biochemistry & Molecular Biology
Giada Cernicchi, Tommaso Felicetti, Stefano Sabatini
Summary: AMR is a complex threat to human health, and blocking bacterial resistance mechanisms is a hot topic in drug discovery. By designing and synthesizing novel EPIs, researchers aim to discover more effective microbial EPIs with improved safety profiles.
Article
Microbiology
Honghao Huang, Peng Wan, Xinyue Luo, Yixing Lu, Xiaoshen Li, Wenguang Xiong, Zhenling Zeng
Summary: Previous analysis has shown that overexpression of MepA is an exact mechanism involved in tigecycline resistance apart from the rpsJ mutation and is usually dependent on the mutant mepR. However, no research has evaluated the effects of diverse mutations discovered in TRSA in MepA. This study explores mutations in the mepA genes and identifies tigecycline resistance-associated mutations T29I, E287G, and T29I+E287G in MepA, demonstrating their role in promoting tigecycline efflux and providing genetic references for identifying TRSA.
MICROBIOLOGY SPECTRUM
(2023)
Article
Medicine, Research & Experimental
Katerina Holasova, Bara Krizkovska, Lan Hoang, Simona Dobiasova, Jan Lipov, Tomas Macek, Vladimir Kren, Katerina Valentova, Tomas Ruml, Jitka Viktorova
Summary: Antibiotic resistance is a serious health problem, and the discovery of new antibiotics alone is no longer sufficient in combating multidrug-resistant infections. Adjuvant therapy and reducing bacterial virulence are gaining importance. Silymarin, a complex of flavonoids and flavonolignans, has a wide range of biological activities and can modulate drug resistance in cancer. This study tested eleven optically pure silymarin flavonolignans and found that some of them can reverse the multidrug resistance phenotype of Staphylococcus aureus and reduce its virulence.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Banani Deka, Mrinaly Suri, Sangita Sarma, Anamika Bora, Tejosmita Sen, Anjum Dihingia, Pallab Pahari, Anil Kumar Singh, Moirangthem Veigyabati Devi
Summary: The study synthesized 17 dihydroquinazoline analogues and found that they significantly reduced drug resistance in S. aureus 1199B as NorA efflux pump inhibitors, with low toxicity in human cells, indicating potential as a therapeutic approach.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Cheng Hong Yap, Abdul Qaiyum Ramle, See Khai Lim, Avinash Rames, Sun Tee Tay, Sek Peng Chin, Lik Voon Kiew, Edward R. T. Tiekink, Chin Fei Chee
Summary: Staphylococcus aureus is an adaptable pathogen that can form biofilms and generate persister cells. In this study, a new compound was synthesized and found to have promising antibiofilm activities against S. aureus.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Marie Jouanne, Sylvain Rault, Anne-Sophie Voisin-Chiret
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2017)
Article
Pharmacology & Pharmacy
A. -C. Groo, M. De Pascale, A. -S. Voisin-Chiret, S. Corvaisier, M. Since, A. Malzert-Freon
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2017)
Article
Chemistry, Organic
Camille Denis, Maryne A. J. Dubois, Anne Sophie Voisin-Chiret, Ronan Bureau, Chulho Choi, James J. Mousseau, James A. Bull
Article
Chemistry, Medicinal
Camille Denis, Jana Sopkova-de Oliveira Santos, Ronan Bureau, Anne Sophie Voisin-Chiret
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Organic
Hedou Damien, Anne Sophie Voisin-Chiret
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Mohammed Benabderrahmane, Ronan Bureau, Anne Sophie Voisin-Chiret, Jana Sopkova-de Oliveira Santos
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2020)
Review
Pharmacology & Pharmacy
Charline Kieffer, Jean Pierre Jourdan, Marie Jouanne, Anne Sophie Voisin-Chiret
DRUG DISCOVERY TODAY
(2020)
Review
Nutrition & Dietetics
Marie Jouanne, Sarah Oddoux, Antoine Noel, Anne Sophie Voisin-Chiret
Summary: A woman's nutritional status during pregnancy and breastfeeding is crucial for both her own health and that of future generations. Different countries have varying recommendations for nutritional supplementation during pregnancy, and the nutritional requirements during pregnancy and lactation may differ due to maternal physiological adaptations.
Article
Chemistry, Medicinal
Mohammed Benabderrahmane, Ronan Bureau, Anne Sophie Voisin-Chiret, Jana Sopkova-de Oliveira Santos
Summary: Detection of cryptic pockets is a challenge in structure-based drug discovery. Computational methods, such as enhanced sampling techniques like Metadynamics, show promise in overcoming experimental limitations but are constrained by variable space.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Review
Biochemistry & Molecular Biology
Arvind Negi, Anne Sophie Voisin-Chiret
Summary: Apoptosis is a highly regulated cellular process and aberration in apoptosis is common in various disorders. Bcl-x(L) is an antiapoptotic protein associated with survival and chemoresistance in cancer and senescent cells. Various Bcl-x(L) inhibitors have been developed, but they have limitations. New pharmacological approaches such as PROTACs and SNIPERs show promise in improving treatment efficacy.
Review
Chemistry, Multidisciplinary
Arvind Negi, Charline Kieffer, Anne Sophie Voisin-Chiret
Summary: Photoswitchable-PROTACs utilize photoswitches to achieve precise control over specific bioactivities, holding potential for clinical applications.
Article
Biochemistry & Molecular Biology
Charline Fagnen, Johanna Giovannini, Marco Catto, Anne Sophie Voisin-Chiret, Jana Sopkova-de Oliveira Santos
Summary: This study investigates the mechanism of neurofibrillary tangles formation and identifies the crucial role of hydrogen bonds in the aggregation process of PHF6. The study also highlights the importance of Tyr310 in the complexation of beta-sheets.
ACS CHEMICAL NEUROSCIENCE
(2022)
Review
Pharmacology & Pharmacy
Arvind Negi, Kavindra Kumar Kesari, Anne Sophie Voisin-Chiret
Summary: Targeting selective estrogen subtype receptors using occupancy-driven pharmacology has its flaws, such as weak binding affinity and continuous dosage requirement. Event-driven pharmacology, such as PROTACs, offers a better approach by degrading the protein of interest (POI). Selective estrogen receptor degraders (SERDs) have become the first-line drug for metastatic ER+ breast cancer, showing promise in overcoming endocrine resistance.
Article
Biochemistry & Molecular Biology
Marc Farag, Charline Kieffer, Nicolas Guedeney, Anne Sophie Voisin-Chiret, Jana Sopkova-de Oliveira Santos
Summary: X-linked inhibitor of apoptosis protein (XIAP) inhibits caspase-3, -7 and -9 to prevent apoptosis. It is overexpressed in cancers and plays a role in cancer cell survival. Inhibition of the XIAP-BIR3 domain and caspase-9 interaction is a promising strategy for cancer treatment, but has side effects. This study developed a theoretical model to design and optimize synthetic XIAP-BIR3 antagonists.
Article
Chemistry, Organic
Peerawat Saejong, Juan J. Rojas, Camille Denis, Andrew J. P. White, Anne Sophie Voisin-Chiret, Chulho Choi, James A. Bull
Summary: Oxetanes and azetidines are of great interest in medicinal chemistry due to their small, polar and non-planar characteristics. They can serve as interesting substitutes for carbonyl-containing functional groups. In this study, a synthesis method for 3,3-disubstituted oxetane- and azetidine-ethers is reported, with a comparison to ester functional group. The tertiary benzylic alcohols of the 4-membered rings are selectively activated using Bronsted acid catalysis, allowing the formation of ethers while maintaining the integrity of the oxetane ring. This approach avoids the use of strong bases and halide alkylating agents and enables the utilization of alcohol libraries. Oxetane ethers demonstrate excellent chemical stability and improved stability compared to analogous esters under basic and reducing conditions.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)