Article
Microbiology
Xuan Wang-Kan, Giovanny Rodriguez-Blanco, Andrew D. Southam, Catherine L. Winder, Warwick B. Dunn, Alasdair Ivens, Laura J. Piddocka
Summary: Our research has demonstrated that the loss of AcrB function in E. coli and S. Typhimurium leads to different biological effects despite conferring drug resistance to the same antibiotics. Additionally, we identified potential natural substrates of AcrB and discovered metabolite classes implicated in the virulence of S. Typhimurium. This information can aid in the development of new efflux inhibitors and potentiate the activity of antibiotics.
Article
Microbiology
Samual C. Allgood, Chih-Chia Su, Amy L. Crooks, Christian T. Meyer, Bojun Zhou, Meredith D. Betterton, Michael R. Barbachyn, Edward W. Yu, Corrella S. Detweiler
Summary: New approaches are needed to combat microbial infections. One strategy is to develop compounds that interfere with bacterial virulence by targeting efflux pumps. By using an in-cell screening platform called SAFIRE, we previously identified small molecules that bind AcrB, inhibit AcrAB-TolC, and do not damage membranes. In this study, we used medicinal chemistry to design analogs with increased potency and found that these analogs bind AcrB in a substrate binding pocket. These analogs have the potential to disrupt infection by preventing the export of bacterial toxic metabolites, host defense factors, and/or antibiotics.
Article
Microbiology
Allea Cauilan, Cristian Ruiz
Summary: This study investigates the potential of sodium malonate as an efflux pump inhibitor to increase antibiotic efficacy against multidrug-resistant bacteria. The results showed that sodium malonate can inhibit the efflux of antibiotics and increase their effectiveness.
Article
Chemistry, Medicinal
Napoleon D'Cunha, Mohammad Moniruzzaman, Keith Haynes, Giuliano Malloci, Connor J. Cooper, Enrico Margiotta, Attilio V. Vargiu, Muhammad R. Uddin, Inga Leus, Feng Cao, Jerry M. Parks, Valentin V. Rybenkov, Paolo Ruggerone, Helen Zgurskaya, John K. Walker
Summary: Antibiotic resistance is an increasingly urgent threat to human health, and multidrug efflux pumps are potential targets for combating this issue. The compound NSC-33353 has been identified as a potent inhibitor of efflux pumps, enhancing antibacterial activity in wild-type cells. Structural modifications of NSC-33353 have led to the development of compounds with improved inhibitory and substrate properties, offering insights into the duality of efflux substrate/inhibitor features and facilitating the development of new efflux pump inhibitors.
ACS INFECTIOUS DISEASES
(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)
Article
Biotechnology & Applied Microbiology
Yuuki Ikehata, Noriyuki Doukyu
Summary: Vanillin improves the organic solvent tolerance of Escherichia coli by enhancing the expression of AcrAB-TolC efflux pump, which is regulated by marA transcription factor. The DacrB mutant is more sensitive to vanillin, but its tolerance can be restored by introducing the acrB gene.
JOURNAL OF BIOSCIENCE AND BIOENGINEERING
(2022)
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
Infectious Diseases
Najwan Jubair, R. Mogana, Ayesha Fatima, Yasir K. Mahdi, Nor Hayati Abdullah
Summary: This study investigates the antibacterial and antibiofilm activities of catechin extracted from Canarium patentinervium Miq. against uropathogenic Escherichia coli. Catechin exhibits significant bactericidal activity and strong synergy with tetracycline. It also reduces E. coli biofilm formation by downregulating the expression of biofilm-related gene acrA.
Article
Biochemistry & Molecular Biology
Ana-Maria Udrea, Andra Dinache, Jean-Marie Pages, Ruxandra Angela Pirvulescu
Summary: The study investigates the potential of BG1189 and BG1190 as efflux pump inhibitors through in silico and molecular docking approaches. The findings suggest that these compounds could be attractive candidates for antimicrobial drugs. UV-Vis absorption spectroscopy and FTIR spectroscopy were utilized to study the stability and effects of laser radiation on the molecules.
Article
Microbiology
Jessica Maldonado, Barbara Czarnecka, Dana E. Harmon, Cristian Ruiz
Summary: Efflux and motility are two key biological functions in bacteria. Recent findings have shown that AcrR, a transcriptional repressor, directly regulates motility in E. coli by repressing the expression of flhDC, which is the master regulator of flagellum biosynthesis and motility genes.
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
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
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
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)
Article
Chemistry, Medicinal
Nina Compagne, Juan-Carlos Jimenez-Castellanos, Virginie Meurillon, Elizabeth Pradel, Anais Vieira Da Cruz, Catherine Piveteau, Alexandre Biela, Maxime Eveque, Florence Leroux, Benoit Deprez, Nicolas Willand, Ruben C. Hartkoorn, Marion Flipo
Summary: Multidrug-resistant Escherichia coli, driven by the AcrAB-TolC tripartite RND efflux pump, is a global public health concern. In this study, pyridylpiperazines were optimized by modifying specific derivatization points to enhance their potency and pharmacokinetic properties. Introduction of a primary amine through ester or oxadiazole based linkers improved the antibiotic boosting potency through AcrB inhibition. The favorable physico-chemical properties and stability of compound 44 make it a promising candidate for future in vivo proof of concept studies.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Orsolya Domotor, Ricardo G. Teixeira, Gabriella Spengler, Fernando Avecilla, Fernanda Marques, Oscar A. Lenis-Rojas, Cristina P. Matos, Rodrigo F. M. de Almeida, Eva A. Enyedy, Ana Isabel Tomaz
Summary: In this study, two Ru(II)-polypyridyl compounds were prepared and characterized. The solid-state structure was confirmed by X-ray diffraction analysis. The solubility, stability, and lipophilicity of the complexes were investigated under physiological mimetic conditions, as well as their potential uptake by passive diffusion. The complexes exhibited cytotoxicity on ovarian and colon cancer cells and induced late apoptosis and necrosis. They showed weak binding to human serum albumin but significant binding to calf thymus DNA.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Chemistry, Medicinal
Andreina Henriquez-Figuereo, Cristina Moran-Serradilla, Eduardo Angulo-Elizari, Carmen Sanmartin, Daniel Plano
Summary: Neglected tropical diseases (NTDs) are a group of infectious diseases caused by protozoa, with a high incidence and prevalence in developing countries. Economic factors hinder the management of these diseases, and there is a lack of effective drugs and high costs. This study aims to identify novel chalcogen-derived molecules against Chagas disease, leishmaniasis, and human African trypanosomiasis (HAT).
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Tatsiana Petrasheuskaya, Ferenc Kovacs, Nora Igaz, Andrea Ronavari, Balint Hajdu, Laura Bereczki, Nora May, Gabriella Spengler, Bela Gyurcsik, Monika Kiricsi, Eva Frank, Eva A. Enyedy
Summary: A series of novel estradiol-based salicylaldehyde (thio)semicarbazones and their Cu(II) complexes were synthesized and characterized. The Cu(II)-estradiol-semicarbazone complex structure was determined by X-ray crystallography. The Cu(II) complexes of estradiol-TSC and its N,N-dimethyl derivative showed high cytotoxicity against cancer cells and significant activity against Staphylococcus aureus bacteria strain. Estradiol-TSCs exhibited efficient antioxidant activity, which was decreased by complexation with Cu(II) ions. The exchange of estrone moiety to estradiol did not significantly affect the physicochemical and biological properties.
Article
Pharmacology & Pharmacy
Janos P. Meszaros, Wolfgang Kandioller, Gabriella Spengler, Alexander Prado-Roller, Bernhard K. Keppler, Eva A. Enyedy
Summary: This study introduces half-sandwich Rh complexes that can be activated in the acidic, extracellular pH of tumor tissue, reducing the side effects and improving the efficacy of chemotherapy.
Article
Biochemistry & Molecular Biology
Nora Astrain-Redin, Irene Talavera, Esther Moreno, Maria J. Ramirez, Nuria Martinez-Saez, Ignacio Encio, Arun K. Sharma, Carmen Sanmartin, Daniel Plano
Summary: Nowadays, Se-containing molecules, such as ebselen, have demonstrated well-established preventive effects against cancer and Alzheimer's disease. In this study, a total of 39 Se-derivatives were synthesized and tested for their antioxidant and antiproliferative activities. Compound 13a showed concentration- and time-dependent radical scavenging activity, while compounds 14a and 17a exhibited high activity in certain cancer cell lines. Compound 14a also showed promising potential as an anti-Alzheimer agent.
Review
Infectious Diseases
Balint Racz, Gabriella Spengler
Summary: Multidrug resistance is a major challenge in the treatment of infectious diseases and cancer, mainly caused by the overexpression of efflux pumps that remove antimicrobial and anticancer agents. Targeting efflux pumps could be a promising approach for the treatment of bacterial infections and cancer. Repurposing existing drugs, such as antidepressants and antipsychotics, may offer a potential solution to the time and cost-intensive process of drug development.
Article
Biochemistry & Molecular Biology
Elek Ferencz, Gabriella Spengler, Istvan Zupko, Martin Vollar, Zoltan Peter Zomborszki, Norbert Kusz, Judit Hohmann, Balazs Kovacs, Dezso Csupor, Eszter Laczko-Zold, Boglarka Csupor-Loffler
Summary: Common ragweed (Ambrosia artemisiifolia L.) is an invasive plant in Europe used in folk medicine. The chemical composition of its above-ground parts is well-studied, but less is known about the metabolites of the roots. In this study, several compounds were isolated from the root extracts, including a new compound called thiophene E (6). Thiophene E exhibited cytotoxic and antiproliferative effects on A-431 epidermoid skin cancer cells. Another compound, taraxerol-3-O-acetate, showed slight antiproliferative effect on gynecological cancer cell lines. These findings highlight the need for further studies on the safety of ragweed root.
ZEITSCHRIFT FUR NATURFORSCHUNG SECTION C-A JOURNAL OF BIOSCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Nadia Ribeiro, Ipek Bulut, Baris Sergi, Vivien Posa, Gabriella Spengler, Giuseppe Sciortino, Vania Andre, Liliana P. Ferreira, Tarita Biver, Valeria Ugone, Eugenio Garribba, Joao Costa-Pessoa, Eva A. Enyedy, Ceyda Acilan, Isabel Correia
Summary: This study reports the synthesis and characterization of a group of benzoylhydrazones and their Cu(II) complexes. The complexes exhibited moderate-to-strong interaction with bovine serum albumin and showed higher antiproliferative activity compared to the corresponding free ligand and cisplatin. Compound 8 demonstrated the most promising properties with low IC50 values, high induction of oxidative stress and DNA damage, resulting in high rates of apoptosis.
FRONTIERS IN CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Balint Racz, Annamaria Kincses, Krisztian Laczi, Gabor Rakhely, Enrique Dominguez-alvarez, Gabriella Spengler
Summary: Recently, the anticancer activity of symmetrical selenoesters was investigated in sensitive and resistant human colon adenocarcinoma cells. The compounds showed synergistic interaction with doxorubicin and exhibited ABCB1 inhibitory and apoptosis-inducing effects. Transcriptome analysis revealed that symmetrical selenoesters may influence the redox state of cells and interfere with metastasis formation.
Editorial Material
Biochemistry & Molecular Biology
Malgorzata Anna Marc, Enrique Dominguez-Alvarez, Claus Jacob
Article
Biochemistry & Molecular Biology
Nora Astrain-Redin, Asif Raza, Ignacio Encio, Arun K. Sharma, Daniel Plano, Carmen Sanmartin
Summary: Oxidative stress provides cancer cells with advantages for disease progression. Se-containing molecules with anticancer and antioxidant activity were synthesized and showed potent radical scavenging and anticancer activity. New Se derivatives resembling natural products exhibited high radical scavenging activity and antiproliferative effects.
Article
Chemistry, Multidisciplinary
Tasneem Sultan Abu Ghazal, Katalin Veres, Livia Vidacs, Nikoletta Szemeredi, Gabriella Spengler, Robert Berkecz, Judit Hohmann
Summary: The chloroform extract of Origanum majorana showed strong antibacterial and antifungal activities. Six compounds were isolated and identified, including furanonaphthoquinones, diterpenes, and flavonoids. Majoranaquinone (1) exhibited potent antibacterial effect and biofilm formation inhibition on various strains, especially in Escherichia coli.
Article
Chemistry, Medicinal
Itziar Galarreta-Rodriguez, Mikel Etxebeste-Mitxeltorena, Esther Moreno, Daniel Plano, Carmen Sanmartin, Saad Megahed, Neus Feliu, Wolfgang J. Parak, Eneko Garaio, Izaskun Gil de Muro, Luis Lezama, Idoia Ruiz de Larramendi, Maite Insausti
Summary: In this study, a drug carrier nanosystem based on Fe3O4 nanoparticles with large heating power was designed. The nanosystem showed high selectivity against colon cancer cells and demonstrated good efficacy as a magnetic hyperthermia inductor.
