Review
Infectious Diseases
Viola Camilla Scoffone, Gabriele Trespidi, Giulia Barbieri, Samuele Irudal, Elena Perrin, Silvia Buroni
Summary: This review summarizes the principal RND efflux pump families described in CF pathogens, with a focus on the main Gram-negative bacterial species, where RND pumps have been associated with MDR phenotypes.
Review
Microbiology
Kunihiko Nishino, Seiji Yamasaki, Ryosuke Nakashima, Martijn Zwama, Mitsuko Hayashi-Nishino
Summary: Multidrug efflux pumps are inner membrane transporters that export multiple antibiotics from bacterial cells, contributing to multidrug resistance. They are abundant in bacteria, and their co-crystal structural analysis reveals drug recognition and export mechanisms, emphasizing the importance of developing inhibitors to combat infectious diseases caused by multidrug-resistant bacteria.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Nidhi Deswal, Ankita Shrivastava, Md Summon Hossain, Parveen Gahlyan, Rashim Bawa, Rinkoo Devi Gupta, Rakesh Kumar
Summary: A series of novel triazole linked isatin-dihydropyridine hybrids have been synthesized and tested for their anti proliferative activity against human cancer cell lines. Compound N2 showed the highest inhibitory action and may be an excellent drug-like candidate for further pursuit.
Article
Chemistry, Physical
C. P. Kaushik, Jyoti Sangwan, Raj Luxmi, Devinder Kumar, Deepak Kumar, Ashutosh Das, Ashwani Kumar, Dharmendra Singh
Summary: A series of anticancer and antioxidant compounds were synthesized through click chemistry method, with some compounds showing promising activity against cancer cell lines and strong antioxidant activity. Molecular docking studies revealed high binding affinities of certain compounds, suggesting their potential as future candidates for anticancer treatment. In-silico ADME studies also indicated good dispositional profile and patient compliance of the synthesized compounds.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Review
Infectious Diseases
Mahdyeh Neghabi Hajiagha, Hossein Samadi Kafil
Summary: Biofilm-related infections are difficult to treat due to their resistance to drugs. Efflux pumps, which play a crucial role in biofilm formation, affect physical-chemical interactions, mobility, gene regulation, quorum sensing, extracellular polymeric substances, and toxic compound extrusion. Understanding the function and identification of efflux pumps in biofilm-forming bacteria will help in choosing effective treatment strategies, including combination with antibiotics.
INFECTION GENETICS AND EVOLUTION
(2023)
Review
Environmental Sciences
Nibedita Dey, C. Kamatchi, A. S. Vickram, K. Anbarasu, S. Thanigaivel, Jeyanthi Palanivelu, Arivalagan Pugazhendhi, Vinoth Kumar Ponnusamy
Summary: The changes in lifestyle and living conditions have affected both humans and microorganisms, leading to the issue of multi-drug resistance. The use of nanotechnology offers hope in overcoming resistance by providing a synergistic effect with antibiotics through nanoparticles. By targeting efflux systems, it might be possible to make previously resistant medications effective again.
ENVIRONMENTAL RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Min Dong, Guili Zheng, Feng Gao, Min Li, Chen Zhong
Summary: A series of dihydroartemisinin-isatin hybrids were designed and synthesized, and their antiproliferative activity against lung cancer cell lines was evaluated. The hybrids showed significant activity, surpassing the activity of dihydroartemisinin and artemisinin. In particular, hybrid 6a demonstrated comparable activity to common chemotherapeutic drugs and showed higher potency against multidrug-resistant lung cancer cell lines. Furthermore, hybrid 6a exhibited good selectivity and stability, making it a promising candidate for further development as an anti-lung cancer chemotherapeutic agent.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Infectious Diseases
Armel Jackson Seukep, Helene Gueaba Mbuntcha, Victor Kuete, Yindi Chu, Enguo Fan, Ming-Quan Guo
Summary: An effective response to antimicrobial resistance (AMR) requires a combination of prevention and treatment. Bacteria have developed strategies, such as over-expression of efflux pumps (EPs), to become resistant to antibiotics. Efforts are focused on developing resistance breakers, including natural plant extracts and alternative methods, to combat AMR.
Review
Biochemistry & Molecular Biology
Manuel F. Varela, Jerusha Stephen, Deeksha Bharti, Manjusha Lekshmi, Sanath Kumar
Summary: Bacterial pathogens resistant to multiple antimicrobial agents through active efflux pose a serious threat to public health. This review discusses recent molecular studies focused on modulating the antimicrobial efflux transporters to restore the clinical efficacy of infectious disease chemotherapy.
Review
Biochemistry & Molecular Biology
Andre Bittencourt Lorusso, Joao Antonio Carrara, Carolina Deuttner Neumann Barroso, Felipe Francisco Tuon, Helisson Faoro
Summary: Antimicrobial resistance is a global public health crisis caused by the emergence of resistant organisms and different mechanisms of antibiotic resistance. Efflux pumps, particularly in Gram-negative bacteria like Pseudomonas aeruginosa, play a significant role in multidrug resistance and extensively drug-resistant bacteria. Understanding their function, structure, and regulation is essential in combating antibiotic resistance and developing new drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Caroline Lopes Martini, Amada Zambrana Coronado, Maria Celeste Nunes Melo, Clarice Neffa Gobbi, Ursula Santos Lopez, Marcos Correa de Mattos, Thais Tavares Amorim, Ana Maria Nunes Botelho, Ana Tereza Ribeiro Vasconcelos, Luiz Gonzaga Paula Almeida, Paul J. Planet, Russolina Benedeta Zingali, Agnes Marie Sa Figueiredo, Bernadete Teixeira Ferreira-Carvalho
Summary: This study has found that Streptococcus pyogenes can form antimicrobial persisters under certain conditions, possibly involving efflux pumps. The persistence phenomenon may be related to factors such as protein synthesis inhibition, cell growth impairment, and efflux pumps.
FRONTIERS IN MICROBIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Sachin Rathod, Pratap Bahadur, Sanjay Tiwari
Summary: alpha-Tocopheryl polyethylene glycol succinate (TPGS) is a safe excipient that can enhance drug solubility and dispersion. Its aggregation behavior can be modulated by other amphiphiles and organic additives, allowing for the development of various drug formulations. TPGS improves drug bioavailability by enhancing permeation and reducing levels of P-glycoproteins.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Magdalena Peruzynska, Aleksandra Borzyszkowska-Ledwig, Jacek G. Sosnicki, Lukasz Struk, Tomasz J. Idzik, Gabriela Maciejewska, Lukasz Skalski, Katarzyna Piotrowska, Pawel Lukasik, Marek Drozdzik, Mateusz Kurzawski
Summary: This study successfully obtained a mitotic-specific inhibitor with high antiproliferative activity and selectivity through structural modifications. By inhibiting tubulin polymerization in a dose-dependent manner, aberrant mitotic spindle formation was induced, leading to cell cycle arrest and apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Qiyuan Zhou, Shu Chen, Zoufeng Xu, Gongyuan Liu, Shuyuan Zhang, Zhigang Wang, Man-Kit Tse, Shek-Man Yiu, Guangyu Zhu
Summary: This study reports the synthesis of Pt-IV complexes bearing axial pyridines through ligand exchange reactions. It was discovered that these axial pyridines can be quickly released after reduction, indicating their potential as axial leaving groups. Two multitargeted Pt-IV prodrugs containing bioactive pyridinyl ligands, a PARP inhibitor and an EGFR tyrosine kinase inhibitor, were successfully obtained using this method. These conjugates show great potential for overcoming drug resistance, with the latter inhibiting the growth of Pt-resistant tumor in vivo. This research expands the synthetic methods for Pt-IV prodrugs and increases the range of bioactive axial ligands that can be conjugated to a Pt-IV center.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Microbiology
Yinhuan Ding, Jingchen Hao, Weijia Xiao, Caihong Ye, Xue Xiao, Chunxia Jian, Min Tang, Guangrong Li, Jinbo Liu, Zhangrui Zeng
Summary: The article "The efficacy of Colistin-resistant strains and the mechanisms of multidrug resistance" discusses the contribution of efflux pumps and their related transcriptional regulators to Colistin resistance, as well as the reverse effect of efflux pump inhibitors. Previous studies have shown a complex regulatory relationship between efflux pumps and their transcriptional regulators, as well as LPS synthesis, transport, and modification. CCCP, NMP, and PA & beta;N can reverse Colistin resistance, highlighting the role of efflux pumps and their potential as adjuvant development. The contribution of efflux pumps to Colistin resistance may also be related to specific genetic backgrounds.
FRONTIERS IN MICROBIOLOGY
(2023)
Review
Chemistry, Organic
Melford Chuka Egbujor, Jorge Garrido, Fernanda Borges, Luciano Saso
Summary: Sulfonamides are known for their diverse biological activities, including antioxidant activity. They have structural diversity and are suitable for drug discovery programs. Despite being extensively used as antibacterial agents, their therapeutic potential as antioxidants has been relatively underexplored. Some sulfonamide derivatives have been found to activate Nrf2, a key process in cellular response to oxidative stress.
MINI-REVIEWS IN ORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Mauricio Tavares Jacques, Luciano Saso, Marcelo Farina
Summary: Neuron-glia interactions are crucial for maintaining the central nervous system's stability. Microglial cells, as important support cells in the brain, play a role in responding to disruptions in this stability. In this study, the researchers investigated the potential protective effects of activated microglia on neuronal cells against ferroptosis, an iron-dependent form of cell death. The findings suggest that activated microglial cell-derived molecules may contribute to the protection of neuronal cells against ferroptosis, highlighting the potential for controlling this cell death mechanism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Gabriel Mendez-Valdes, Vicente Perez-Carreno, Maria Chiara Bragato, Malthe Hundahl, Silvia Chichiarelli, Luciano Saso, Ramon Rodrigo
Summary: Ischemia/reperfusion injury is a detrimental process during cardiac interventions, leading to activation of cell death pathways and increased cardiovascular risk. Multiple NADPH oxidases, activated via AT1R occupancy, contribute to the generation of ROS. In addition, ROS can induce proinflammatory responses. On the other hand, the Ang II/AT2R axis exerts cardioprotective effects. AT1R blockers may be used to inhibit the Ang II/AT1R axis and reduce ROS burst, while combination with other cardioprotective agents shows promising outcomes in experimental studies.
Article
Biochemistry & Molecular Biology
Kristina Kostic, Jasmina Brboric, Giovanna Delogu, Milena R. Simic, Stevan Samardzic, Zoran Maksimovic, Maria Antonietta Dettori, Davide Fabbri, Jelena Kotur-Stevuljevic, Luciano Saso
Summary: A comparative study was conducted to evaluate the antioxidant potential of natural phenols (zingerone, curcumin, raspberry ketone, magnolol) and their synthesized derivatives. The study measured the antioxidant efficiency in blood serum obtained from healthy individuals, before and after adding the pro-oxidant tert-butyl hydroperoxide (TBH). It was found that curcumin, raspberry ketone, magnolol, and the synthesized derivative of zingerone demonstrated remarkable antioxidant effects in the blood serum of healthy individuals. Moreover, a combination of zingerone and curcumin exhibited synergistic antioxidant effects.
Editorial Material
Biochemistry & Molecular Biology
Sarmistha Saha, Luciano Saso, Guliz Armagan
Review
Biochemistry & Molecular Biology
Melford C. Egbujor, Paolo Tucci, Ugomma C. Onyeije, Chigbundu N. Emeruwa, Luciano Saso
Summary: A wide range of nitrogen heterocyclic compounds have been used in clinical practice, with a major presence in FDA-approved drugs. These compounds have shown significant activation of the NRF2/ARE signaling pathway and upregulation of NRF2-dependent genes, highlighting their importance in studying the pharmacological effects of N-based heterocyclic moieties. Nitrogen heterocycles also exhibit antioxidant and anti-inflammatory activities, making them of great interest for research in neuroinflammation and oxidative stress-mediated diseases. A comprehensive review on the NRF2-inducing activities of N-based heterocycles and their derivatives will provide valuable insights for therapeutic prospects and stimulate innovative research in this field.
Article
Oncology
Salman Ahmed, Waqas Alam, Michael Aschner, Rosanna Filosa, Wai San Cheang, Philippe Jeandet, Luciano Saso, Haroon Khan
Summary: Neuroblastoma is a common solid tumor in pediatric patients that arises from sympathetic nervous system cells. Current treatments have limited success, leading to high mortality and relapse rates. Marine cyanobacteria, which contain bioactive metabolites, have shown promise as alternative treatments. This review focuses on the anticancer effects of cyanobacterial peptides against neuroblastoma. Marine peptides offer advantages such as small size, easy manufacturing, ability to cross cell membranes, minimal drug interactions, little impact on the blood-brain barrier, and targeting capabilities. The review discusses the cytotoxic effects of cyanobacterial peptides, including apoptosis, caspase activation, cell cycle arrest, sodium channel blocking, autophagy, and anti-metastasis properties.
Review
Pharmacology & Pharmacy
Amin Iranpanah, Leila Kooshki, Seyed Zachariah Moradi, Luciano Saso, Sajad Fakhri, Haroon Khan
Summary: As a major public health concern, neurological diseases and neurodegenerative diseases significantly impact the growing aging population, leading to disability and mortality. Apoptosis, inflammation, and oxidative stress play crucial roles in the development of neurodegenerative diseases, with the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway being a key player. The blood-brain barrier poses challenges for drug delivery, but exosomes have emerged as potential nano-sized vehicles for central nervous system drug delivery due to their ability to cross the blood-brain barrier and their unique characteristics such as low immunogenicity and great tissue/cell penetration capabilities. This systematic review highlights the therapeutic potential of exosomes targeting the PI3K/Akt/mTOR signaling pathway in the context of neurodegenerative diseases and neurological diseases.
Review
Biochemistry & Molecular Biology
Gabriel Mendez-Valdes, Francisca Gomez-Hevia, Maria Chiara Bragato, Jose Lillo-Moya, Catalina Rojas-Sole, Luciano Saso, Ramon Rodrigo
Summary: Breast cancer is the most common malignant neoplastic disease in women, and its treatment depends on patient and tumor characteristics. The overexpression of the HER2 receptor, found in 15-25% of tumors, is associated with aggressive behavior and poor prognosis. Trastuzumab, a monoclonal antibody used as targeted therapy against HER2 receptor overexpression, has a major concern of cardiotoxicity. This review aims to explore the use of antioxidants as adjuvant therapy to prevent trastuzumab-induced cardiac toxicity and improve its safety profile.
Review
Biochemistry & Molecular Biology
Somayyeh Ghareghomi, Faezeh Moosavi-Movahedi, Luciano Saso, Mehran Habibi-Rezaei, Ali Khatibi, Jun Hong, Ali A. Moosavi-Movahedi
Summary: Oxidative stresses play a pivotal role in various pathophysiological conditions. The Keap1/Nrf2 pathway is a dual-edged sword with beneficial effects on both normal and cancer cells by regulating endogenous antioxidant enzymes. Targeting the Nrf2/HO-1 axis is considered a novel strategy for cancer treatment, especially in lung cancer.
Article
Neurosciences
Lidia Wlodarczyk, Natalia Cichon, Michal Seweryn Karbownik, Luciano Saso, Joanna Saluk, Elzbieta Miller
Summary: This study aims to identify biomarkers that can predict brain repair ability and estimate the outcome of stroke by examining the expression of VEGF, IGF-1, and MMP-9 proteins and their genes. The results showed significant changes in clinical parameter estimations, as well as MMP9 and VEGF protein and mRNA expression over the rehabilitation process. The combined expression of MMP9 protein and mRNA may serve as a useful biomarker for cognitive improvement in post-stroke patients.
Review
Chemistry, Medicinal
Darinka Gjorgieva Ackova, Viktorija Maksimova, Katarina Smilkov, Brigitta Buttari, Marzia Arese, Luciano Saso
Summary: The transcription factor NRF2 plays a crucial role in regulating various genes to protect cells from stress-induced damage. While it is important for maintaining cellular redox balance, excessive activation of NRF2 in cancer cells can contribute to their survival and resistance to therapy. Alkaloids derived from natural sources have been found to inhibit NRF2 activity and enhance the efficacy of cancer treatments. Further research is necessary to explore the potential of these alkaloids as promising targets for anticancer therapy.
Review
Chemistry, Medicinal
Lozan Todorov, Luciano Saso, Irena Kostova
Summary: Coumarins, as a class of phenolic compounds widely found in plants, have diverse applications in various fields, such as everyday life, organic synthesis, and medicine. Their unique structure with excellent charge and electron transport properties makes them well-known for their broad spectrum of physiological effects. In recent years, research efforts have been focused on synthesizing and examining synthetic coumarin derivatives to develop potential drugs with enhanced or novel effects. This review aims to summarize the prominent findings from investigations into the antioxidant properties of novel coumarin compounds over the past five years.
Article
Chemistry, Physical
Sara Ranjbar, Faramak Faramin Lashkarian, Mehdi Khoshneviszadeh, Fatemeh Moosavi, Amirhossein Sakhteman, Farshid Zargari, Luciano Saso, Omidreza Firuzi, Najmeh Edraki
Summary: In this study, novel 5-oxo-hexahydroquinoline derivatives were synthesized and tested for their ability to reverse multidrug resistance (MDR) in cancer cells overexpressing P-glycoprotein (P-gp). Most of the compounds showed enhanced intracellular accumulation of rhodamine 123, a P-gp substrate, and some exhibited better results than the established P-gp inhibitor verapamil. Certain compounds also effectively reversed resistance to doxorubicin and showed cytotoxic effects against leukemia and colon cancer cells. Molecular simulation analysis confirmed the interaction of selected compounds with the drug-substrate binding site of P-gp.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Review
Biochemistry & Molecular Biology
Maurizio Sorice, Elisabetta Profumo, Antonella Capozzi, Serena Recalchi, Gloria Riitano, Benedetta Di Veroli, Luciano Saso, Brigitta Buttari
Summary: Oxidative stress plays a crucial role in the initiation and progression of Antiphospholipid Antibody Syndrome (APS), a systemic autoimmune disease characterized by thrombosis and pregnancy morbidity. It affects various biological processes and signaling pathways, leading to dysfunctional immune responses, inflammation, apoptosis, autophagy deregulation, and impaired mitochondrial function. The imbalance between oxidation and antioxidant mechanisms in APS patients reflects disease progression. This review focuses on the role of oxidative stress in APS and explores potential therapeutic approaches, such as food supplements and NRF2 activators, to reduce the clinical complications associated with APS.