Article
Chemistry, Medicinal
Kritika Engle, Gautam Kumar
Summary: Chemotherapy is a common treatment for cancer, but its drawbacks include lack of selectivity and development of drug resistance. Multidrug resistance refers to low sensitivity of specific cells to anticancer drugs, which is mainly caused by overexpression of multidrug efflux systems.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Sandra Kovachka, Giuliano Malloci, Meline Simsir, Paolo Ruggerone, Stephane Azoulay, Isabelle Mus-Veteau
Summary: This review focuses on the biological evaluation and molecular mechanistic insights of inhibitors of the drug efflux activity of the Hedgehog receptor Patched1 (Ptch1). Ptch1 is known to be over-expressed in many types of cancers and plays a role in the resistance to chemotherapy of cancer cells. Inhibition of Ptch1 has been shown to improve the efficacy of chemotherapy without toxicity for healthy cells or potential side effects.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ewa Zeslawska, Waldemar Tejchman, Annamaria Kincses, Gabriella Spengler, Wojciech Nitek, Grzegorz Zuchowski, Ewa Szymanska
Summary: Multidrug resistance (MDR) is a major reason for the failure of anticancer and antiviral chemotherapies. In this study, a series of newly synthesized 5-arylidenerhodanines were investigated for their ability to inhibit the ABCB1 efflux pump in mouse T-lymphoma cancer cells. Compounds with a triphenylamine moiety and the carboxyl group showed strong inhibitory effects, with over 17-fold higher potency than verapamil. The cytotoxic and antiproliferative effects of these compounds on T-lymphoma cells were also examined.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yasmeen Cheema, Yusra Sajid Kiani, Kenneth J. J. Linton, Ishrat Jabeen
Summary: Researchers developed a pharmacophore model based on the cryo-EM structure of ABCB1 to screen for new inhibitors, resulting in the identification of six potential inhibitors with distinct chemistries and favorable properties. The compounds exhibited low nanomolar range inhibitory concentrations and two of them were able to resensitize ABCB1-expressing cells to taxol. This study demonstrates the utility of cryo-electron microscopy in drug identification and design.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Zhemin Zhang, Christopher E. Morgan, Robert A. Bonomo, Edward W. Yu
Summary: Acinetobacter baumannii, a highly antibiotic-resistant Gram-negative pathogen, is a significant global health threat. The presence of multidrug efflux pumps within the bacterium is a major cause of failure of drug-based treatments.
Review
Microbiology
Jerusha Stephen, Manjusha Lekshmi, Parvathi Ammini, Sanath H. Kumar, Manuel F. Varela
Summary: Infectious diseases caused by bacteria of the Vibrio genus have significant impacts on human health. The mechanisms of antimicrobial resistance in Vibrio spp. include biofilm formation and active antimicrobial efflux. Understanding these antimicrobial transport systems is important for studying Vibrio spp. pathogenesis and virulence.
Article
Microbiology
Zhemin Zhang, Christopher E. Morgan, Meng Cui, Edward W. Yu
Summary: In this study, cryo-EM structures of the AcrD aminoglycoside efflux pump in the absence and presence of bound gentamicin were reported. It is suggested that this pump is capable of capturing aminoglycosides from the central cavity of the AcrD trimer. The results demonstrate that AcrD utilizes charged residues to bind and export drugs, mediating resistance to these antibiotics.
Article
Microbiology
Silvia Gervasoni, Jitender Mehla, Charles R. Bergen, Inga V. Leus, Enrico Margiotta, Giuliano Malloci, Andrea Bosin, Attilio V. Vargiu, Olga Lomovskaya, Valentin V. Rybenkov, Paolo Ruggerone, Helen I. Zgurskaya
Summary: This study investigated the dynamics of MexB interactions with its ligands using machine learning, computational and experimental approaches. The results showed that MexB ligands can be effectively expelled or hindered in the transporter cycle based on their interactions with specific residues in MexB binding sites. The findings indicate that MexB ligands fit into a substrate-inhibitor spectrum depending on their physico-chemical properties. This molecular-level information is important for the rational design of new inhibitors and antibiotics less susceptible to the efflux mechanism.
Review
Infectious Diseases
Song Zhang, Jun Wang, Juhee Ahn
Summary: The excessive use of antibiotics has led to the emergence of multidrug-resistant pathogens, posing challenges to clinical management and food control. The discovery of novel antibiotic potentiators can be useful for the treatment of bacterial infections. This review provides a comprehensive summary of advances in novel EPI discovery and the potential strategies for fighting antibiotic resistance.
Article
Microbiology
Seiji Yamasaki, Naoki Koga, Martijn Zwama, Keisuke Sakurai, Ryosuke Nakashima, Akihito Yamaguchi, Kunihiko Nishino
Summary: This study found that different Trp mutations at different locations in the structure of MexB can affect the inhibitory effect of EPIs, without affecting the function of the efflux pumps.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Christopher E. Morgan, Zhemin Zhang, Robert A. Bonomo, Edward W. Yu
Summary: Antibiotic resistance is a serious global health threat, and in the Gram-negative bacteria Acinetobacter baumannii, the multidrug efflux pump (AdeJ) is a major resistance determinant. This study uses cryo-EM to reveal the structure of the novel tetracycline antibiotic TP-6076 bound to AdeJ and the ribosome, providing insights into their binding mechanisms.
Article
Microbiology
Christopher E. Morgan, Zhemin Zhang, Robert A. Bonomo, Edward W. Yu
Summary: This study demonstrates how the multidrug efflux pump AdeJ recognizes the experimental tetracycline antibiotic TP-6076 and inhibits its interaction with the A. baumannii ribosome using cryo-EM. Exploiting the differences in binding modes between AdeJ and the ribosome with TP-6076 may guide future drug development for combating antibiotic-resistant A. baumannii and other multidrug-resistant bacteria.
Article
Infectious Diseases
Hsu-Feng Lu, Yu-Chieh Tsai, Li-Hua Li, Yi-Tsung Lin, Tsuey-Ching Yang
Summary: AzoR, a LysR-type transcriptional regulator, was found to negatively regulate the expression of the smeU1VWU2X operon and the SmeVWX pump-mediated antibiotic resistance in Stenotrophomonas maltophilia.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Infectious Diseases
Ruichao Li, Kai Peng, Xia Xiao, Yuan Liu, Daxin Peng, Zhiqiang Wang
Summary: This study provides the first report of co-occurrence of bla(VIM-2) and tmexCD1-toprJ1 in one plasmid in P. putida. The emergence of plasmid-mediated carbapenem and tigecycline resistance genes in P. putida from migratory birds highlights the importance of surveillance of novel mobile resistance genes in migratory birds.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Agronomy
Tan Dai, Zhiwen Wang, Xingkai Cheng, Huige Gao, Li Liang, Pengfei Liu, Xili Liu
Summary: Both fungicide efflux and detoxification metabolism are involved in the resistance mechanisms of Phytophthora capsici to SYP-14288.
PEST MANAGEMENT SCIENCE
(2022)
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
Biochemistry & Molecular Biology
Tamas Pivarcsik, Vivien Posa, Hilda Kovacs, Nora May, Gabriella Spengler, Szonja P. Posa, Szilard Toth, Zeinab Nezafat Yazdi, Csilla Ozvegy-Laczka, Imre Ugrai, Istvan Szatmari, Gergely Szakacs, Eva A. Enyedy
Summary: This article investigates a novel 5-nitro-8-hydroxyquinoline-proline hybrid and its Rh(eta(5)-C5Me5) and Ru(eta(6)-p-cymene) complexes, which have excellent solubility in water and show inhibitory effects on sensitive and multidrug-resistant cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Shirley A. R. Sancha, Nikoletta Szemeredi, Gabriella Spengler, Maria-Jose U. Ferreira
Summary: In order to overcome multidrug resistance in cancer chemotherapy, lycorine, a major Amaryllidaceae alkaloid isolated from Pancratium maritimum, was derivatized to obtain 31 new compounds. These compounds showed significant activity in the study of anticancer drug resistance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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
Pawel Zagrodzki, Agnieszka Wiesner, Monika Marcinkowska, Marek Jamrozik, Enrique Dominguez-Alvarez, Katarzyna Bierla, Ryszard Lobinski, Joanna Szpunar, Jadwiga Handzlik, Agnieszka Galanty, Shela Gorinstein, Pawel Pasko
Summary: Due to selenium deficiency in humans, the search for new organic molecules containing this element in plant biofortification is important. This study evaluated selenium organic esters based on benzoselenoate scaffolds, with additional halogen atoms and various functional groups. The study aimed to discover the relationships between molecular characteristics of these compounds and the amount of sulfur phytochemicals in kale sprouts. The statistical model revealed a correlation structure between the molecular descriptors of selenium compounds and the biochemical features of the sprouts.
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.
Article
Plant Sciences
Bara Krizkovska, Lan Hoang, Daniela Brdova, Kristyna Klementova, Nikoletta Szemeredi, Anna Louckova, Olga Kronusova, Gabriella Spengler, Petr Kastanek, Jana Hajslova, Jitka Viktorova, Jan Lipov
Summary: Salvia officinalis L., Sambucus nigra L., Matricaria chamomilla L., Agrimonia eupatoria L., Fragaria vesca L., and Malva sylvestris L. are plants that have been used in European folk medicine for treating skin wounds and infections. This study investigated their potential as adjuvants for the treatment of antibiotic-resistant bacteria. The results showed that Malva sylvestris had the highest antimicrobial activity, while Fragaria vesca and Sambucus nigra demonstrated potential as efflux pump inhibitors. Overall, these plants have potential for improving antibiotic treatment.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Janos P. Meszaros, Hilda Kovacs, Gabriella Spengler, Ferenc Kovacs, Eva Frank, Eva A. Enyedy
Summary: A salicylhydroxamic acid-estradiol hybrid molecule (E2HA) was synthesized, which forms high-stability complexes with essential metal ions (iron, copper) and exhibits moderate anticancer activity in human cancer cell lines.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
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.