Article
Microbiology
Voon Ong, Sarah Wills, Deborah Watson, Taylor Sandison, Shawn Flanagan
Summary: Rezafungin is primarily excreted through feces in rats, monkeys, and humans, with unchanged drug as the main excretion product. After intravenous administration, rezafungin has a slow metabolism and elimination rate.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Anna Dahlman, Manoj Puthia, Jitka Petrlova, Artur Schmidtchen, Ganna Petruk
Summary: TCP-25, an antimicrobial peptide with antibacterial and immunomodulatory effects, demonstrates the ability to inhibit Candida growth and reduce associated inflammation. Both in vitro and in vivo experiments validate the therapeutic potential of TCP-25 against Candida infections.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Pharmacology & Pharmacy
Nilesh R. Rarokar, Sunil S. Menghani, Deweshri R. Kerzare, Pramod B. Khedekar, Ashish P. Bharne, Abdulhakeem S. Alamri, Walaa F. Alsanie, Majid Alhomrani, Nagaraja Sreeharsha, Syed Mohammed Basheeruddin Asdaq
Summary: The present study developed a drug-loaded solid lipid nanoparticle hydrogel for improved antifungal efficacy. The hydrogel demonstrated sustained drug release over 24 hours and showed better physical stability at lower temperatures.
Article
Biochemistry & Molecular Biology
Yue Zhang, Qiuhao Li, Wen Chao, Yulin Qin, Jiayan Chen, Yingwen Wang, Runhui Liu, Quanzhen Lv, Jinxin Wang
Summary: Nowadays, discovering new skeleton antifungal drugs is crucial for addressing clinical fungal infections. In this study, the structure-activity relationship of pyrylium salt SM21 was investigated, and a series of derivatives were synthesized. The synthesized compounds showed improved antifungal activities, with one compound, XY12, displaying stronger antifungal effects and decreased cytotoxicity compared to SM21. XY12 also had efficacy against fluconazole-resistant Candida species and improved the survival rate in mice with systemic Candida infection. These findings suggest the potential of structural modification of pyrylium salts in discovering new antifungal drugs.
Article
Microbiology
Laura S. Burrack, Robert T. Todd, Natthapon Soisangwan, Nathan P. Wiederhold, Anna Selmecki
Summary: Antifungal drug resistance and tolerance are a serious threat to global public health. This study investigated the evolution of drug resistance in Candida auris and found rapid acquisition of resistance mutations and the stability of resistance in the absence of drugs. The genetic background of clinical isolates was also found to affect the evolutionary potential and acquisition of resistance. These findings highlight the high stability and high rates of acquisition of antifungal resistance in C. auris, which can lead to the evolution of pan-resistant isolates in clinical settings.
Article
Microbiology
Sarah R. Beattie, Taiwo Esan, Robert Zarnowski, Emily Eix, Jeniel E. Nett, David R. Andes, Timothy Hagen, Damian J. Krysan
Summary: New antifungal therapies are needed for various fungal infections, including biofilms and drug-resistant strains. A novel keto-alkyl-pyridinium scaffold has been identified with broad spectrum activity against medically important fungi. This class of molecules shows potential for non-systemic applications.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Li Wang, Fan Wu, Jia Xu, Yu Wang, Weidong Fei, Hui Jiang, Peiwu Geng, Quan Zhou, Shuanghu Wang, Yongquan Zheng, Huadong Deng
Summary: Drug-drug interactions (DDIs) between pyrotinib and azole antifungal drugs were studied to evaluate their effects on the pharmacokinetics of pyrotinib. The in vitro experiments showed that ketoconazole and fluconazole could significantly decrease the clearance rate of pyrotinib, while itraconazole had no impact. In vivo studies further confirmed that coadministration with ketoconazole or fluconazole resulted in increased plasma concentration and decreased clearance rate of pyrotinib.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yi Gong, Haoyi Li, Fei Wu, Yishuai Li, Shicui Zhang
Summary: Derived from AP-2 complex subunit mu-A, the short peptide AP10W exhibits notable antifungal activities against Candida albicans and Aspergillus fumigatus. It inhibits fungal biofilm formation and reduces pre-established fungal biofilms. AP10W acts through various mechanisms including interaction with fungal cell walls, enhancement of cell wall permeability, membrane depolarization induction, and increase in intracellular ROS generation. It shows low toxicity towards mammalian cells and promotes wound healing in C. albicans-infected skin.
Article
Microbiology
Yu Zhang, Yan-Chao Liu, Si-Min Chen, Hui Zong, Wei-Tong Hou, Xi-Ran Qiu, Shi-Yu Guo, Yu-Fang Sun, Yuan-Ying Jiang, Mao-Mao An, Hui Shen
Summary: This study aimed to develop anidulafungin-loaded Human Serum Albumin nanoparticles to enhance its solubility and antifungal efficacy. The results showed that the nanoparticles improved water solubility of anidulafungin, exhibited stronger antifungal effects in vitro, and prolonged survival time in a murine model of invasive candidiasis compared to the free drug. The developed nanoparticles have the potential to improve drug administration and therapeutic outcomes for fungal diseases.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Guru R. Valicherla, Roshan A. Katekar, Shailesh Dadge, Mohammed Riyazuddin, Anees A. Syed, Sandeep K. Singh, Athar Husain, Muhammad Wahajuddin, Jiaur R. Gayen
Summary: This study investigates the pharmacokinetic properties of PSTi8 in Sprague Dawley rats for the first time. The results show that PSTi8 has high solubility and plasma protein binding, stability, and good bioavailability in rats. These findings support the development of PSTi8 as an antidiabetic agent.
Article
Chemistry, Medicinal
Sarah Lazzaro, Mark A. West, Soraya Eatemadpour, Bo Feng, Manthena V. S. Varma, A. David Rodrigues, Csilla Temesszentandrasi-Ambrus, Peter Kovacs-Hajdu, Zsuzsanna Nerada, Zsuzsanna Gaborik, Chester Costales
Summary: This study evaluated the impact of potential IC50 discrepancies between two commonly utilized assay methods (cell-based and vesicle-based) on P-gp. Non-P-gp substrates showed good correlation between the two methods, while IC50s of P-gp substrates were lower in the vesicle assays. IC50s obtained from two independent laboratories using the same method showed good correlation.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Microbiology
Giovanna Ginestra, Teresa Gervasi, Francesca Mancuso, Federica Bucolo, Laura De Luca, Rosaria Gitto, Davide Barreca, Giuseppina Mandalari
Summary: In this study, a series of arylsulfonamide compounds were screened and the structure-activity relationship was established based on a hit compound. The antifungal activity against various Candida species was tested, and cytotoxicity was evaluated. These findings could contribute to the development of novel topical therapeutics for fungal infections.
Article
Biochemistry & Molecular Biology
Kang Ding, Panpan Shen, Zhongwen Xie, Lifang Wang, Xiangli Dang
Summary: Candida albicans infections often require novel antifungal drugs. The potential antimicrobial peptide P256 demonstrated antifungal activity against C. albicans, showing synergism when combined with amphotericin B, and exerting multiple effects on the fungi.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Katherine Miranda-Cadena, Cristina Marcos-Arias, Estibaliz Mateo, Jose Manuel Aguirre-Urizar, Guillermo Quindos, Elena Eraso
Summary: The study evaluated the effects of three phytocompounds on Candida planktonic and sessile cells, with cinnamaldehyde being the most active in inhibiting biofilm adhesion, while carvacrol and thymol significantly reduced both mature biofilm biomass and metabolic activity. These results highlight the potential of cinnamaldehyde, carvacrol, and thymol as promising alternatives for candidiasis treatment and emphasize the need for further research on their safety, toxicity, pharmacodynamics, and pharmacokinetics.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Dermatology
Gabriele Sass, David J. J. Larwood, Marife Martinez, David A. A. Stevens
Summary: This study investigated the therapeutic effect of Nikkomycin Z on disseminated candidiasis in mice. The results showed that Nikkomycin Z had a significant impact on the survival rate of mice, but it did not completely cure the infection. The inhibitory effect of Nikkomycin Z in exogenous infections may be related to its concentration in the target tissue and its action on mycelial formation.
Article
Biochemistry & Molecular Biology
Claudia Ardino, Filomena Sannio, Carolina Pasero, Lorenzo Botta, Elena Dreassi, Jean-Denis Docquier, Ilaria D'Agostino
Summary: Trifluoroacetic acid (TFA) is commonly used in synthetic strategies due to its strong acidity and low boiling point. However, residual amounts of TFA may affect the accuracy of cellular assays. This study evaluates the effect of different counterions on the biological activity of an antibacterial compound and optimizes the preparation methods.
MOLECULAR DIVERSITY
(2023)
Article
Biochemistry & Molecular Biology
Annalaura Brai, Federica Poggialini, Chiara Vagaggini, Claudia Pasqualini, Sauro Simoni, Valeria Francardi, Elena Dreassi
Summary: A novel, cheap and convenient toxicity model using Tenebrio molitor coleoptera (TMC) was developed for preliminary evaluation of drug safety and metabolite formation. The results demonstrate that TMC can be used as a preliminary toxicity model to assess the safety of experimental compounds and the formation of main metabolites, and to reduce the costs and number of rodents, according to 3R principles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Domenico Pascucci, Adriano Grossi, Alberto Lontano, Eleonora Marziali, Mario Cesare Nurchis, Vincenzo Maria Grassi, Matteo Raponi, Giuseppe Vetrugno, Giovanni Capelli, Giovanna Elisa Calabro, Domenico Staiti, Maurizio Sanguinetti, Gianfranco Damiani, Patrizia Laurenti
Summary: This study evaluates the duration of protection provided by the booster dose of Pfizer-BioNTech BNT162b2 mRNA vaccine in healthcare workers and analyzes the factors associated with post-booster vaccination infections. The study found that the risk of becoming infected with SARS-CoV-2 increased over time, and it was significantly higher for females, younger patients, and individuals who received a hybrid immunity. The study highlights the importance of continuous monitoring of vaccine-induced immunogenicity.
Article
Infectious Diseases
Delia Mercedes Bianco, Flavio De Maio, Giulia Santarelli, Ivana Palucci, Alessandro Salustri, Giada Bianchetti, Giuseppe Maulucci, Franco Citterio, Maurizio Sanguinetti, Enrica Tamburrini, Michela Sali, Giovanni Delogu
Summary: Despite being investigated as a host-directed therapy in treating tuberculosis, Everolimus showed no direct or indirect activity against Mycobacterium tuberculosis (Mtb). Even in an immunosuppressed patient, Everolimus did not affect the viability of Mtb and had minimal impact in host cells during infection. This case emphasizes the importance of careful drug repurposing and pre-clinical experimental studies.
Review
Pharmacology & Pharmacy
Francesco Melfi, Simone Carradori, Andrea Angeli, Ilaria D'Agostino
Summary: In the past 5 years, extensive research has been conducted on the biological potential of natural products as human monoamine oxidase B (hMAO-B) inhibitors. However, natural compounds often face pharmacokinetic issues, such as poor solubility, extensive metabolism, and low bioavailability.
EXPERT OPINION ON DRUG DISCOVERY
(2023)
Article
Biochemistry & Molecular Biology
Flavio De Maio, Giacomo Grotti, Francesco Mariani, Danilo Buonsenso, Giulia Santarelli, Delia Mercedes Bianco, Brunella Posteraro, Maurizio Sanguinetti, Claudia Rendeli
Summary: It was previously believed that the human bladder is sterile, but recent advances in molecular biology have shown the presence of microorganisms in the urinary tract. Understanding the relationship between urobiota and urinary tract disorders has become a significant research focus. Patients with spina bifida (SB), a condition that can lead to neurogenic bladder and increased susceptibility to urinary tract infections, often undergo clean intermittent catheterization (CIC) for treatment. This study aims to investigate the urobiota composition in SB patients compared to healthy controls and explore the urobiota characteristics in relation to CIC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Lucrezia Laterza, Lorenza Putignani, Carlo Romano Settanni, Valentina Petito, Simone Varca, Flavio De Maio, Gabriele Macari, Valerio Guarrasi, Elisa Gremese, Barbara Tolusso, Giulia Wlderk, Maria Antonia Pirro, Caterina Fanali, Franco Scaldaferri, Laura Turchini, Valeria Amatucci, Maurizio Sanguinetti, Antonio Gasbarrini
Summary: This study investigated the effectiveness of gut microbiota modulation for enhancing recovery after COVID-19. A pilot interventional study was conducted with twenty recently recovered COVID-19 patients to explore the impact of a mixed probiotic containing Lactobacilli, Bifidobacteria, and Streptococcus thermophilus on gastrointestinal symptoms, inflammation, intestinal barrier integrity, and gut microbiota profile. Various markers and computational algorithms were utilized to evaluate the outcomes before and after 8 weeks of probiotic supplementation. The results showed a significant reduction in inflammatory markers and an increase in Bifidobacteria at T-1, indicating potential anti-inflammatory effects and the influence of probiotics on gut microbiota composition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Annalaura Brai, Federica Poggialini, Claudia Pasqualini, Claudia Immacolata Trivisani, Chiara Vagaggini, Elena Dreassi
Summary: Vaccines are crucial for preventing pathogen diffusion and cancer. The addition of adjuvants enhances the immune response to antigens, improving the effectiveness and duration of protection. The search for new adjuvants has increased in recent decades, uncovering novel classes and mechanisms of action, but there is still much to learn.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Lorenzo Jacopo Ilic Balestri, Claudia Immacolata Trivisani, Francesco Orofino, Diego Fiorucci, Giuseppina Ivana Truglio, Ilaria D'Agostino, Federica Poggialini, Lorenzo Botta, Jean-Denis Docquier, Elena Dreassi
Summary: Our research group has been studying the development of macrocyclic amidinoureas (MCAs) as antifungal agents. Through in silico target fishing study, we identified chitinases as one of their potential targets. Compound 3f emerged as a promising inhibitor of acidic mammalian chitinase (AMCase) with improved potency and selectivity.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Medicinal
Ilaria D'Agostino, Susi Zara, Simone Carradori, Viviana De Luca, Clemente Capasso, Clemens H. M. Kocken, Anne-Marie Zeeman, Andrea Angeli, Fabrizio Carta, Claudiu T. Supuran
Summary: The hybrid compounds synthesized in this study, which combine the Artesunate core with a sulfonamide moiety, showed high inhibition potency against the protozoan PfCA, while exhibiting low cytotoxic effects on human cells, indicating a wide therapeutic window.
Article
Chemistry, Medicinal
German Benito, Ilaria D'Agostino, Simone Carradori, Marialuigia Fantacuzzi, Mariangela Agamennone, Valentina Puca, Rossella Grande, Clemente Capasso, Fabrizio Carta, Claudiu T. Supuran
Summary: In this study, dual-acting antibacterial agents containing Erlotinib were synthesized and evaluated. Some of the compounds showed strong inhibitory activity against Helicobacter pylori carbonic anhydrase and good antibacterial activity against H. pylori. Computational studies provided insights into the binding mode of these compounds.
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Nutrition & Dietetics
Giada Bianchetti, Flavio De Maio, Alessio Abeltino, Cassandra Serantoni, Alessia Riente, Giulia Santarelli, Maurizio Sanguinetti, Giovanni Delogu, Roberta Martinoli, Silvia Barbaresi, Marco De Spirito, Giuseppe Maulucci
Summary: The human gut microbiome plays a significant role in human health and disease development. Recent advancements in technology have allowed for a better understanding of its composition and functions. Diet, specifically, has been found to shape the gut microbiome, affecting its diversity, population size, and metabolism. Personalized nutrition, based on individual characteristics, has shown promise in directly impacting the gut microbiome. Longitudinal studies are necessary to fully comprehend the long-term effects of specific diets and food components on the gut microbiome, as well as the variations between individuals. Accurate methods of collecting dietary data and the application of machine learning techniques hold immense potential in understanding the gut microbiome's response to diet and providing tailored lifestyle recommendations.
Article
Chemistry, Medicinal
Federica Poggialini, Chiara Vagaggini, Annalaura Brai, Claudia Pasqualini, Anna Carbone, Francesca Musumeci, Silvia Schenone, Elena Dreassi
Summary: Although oral therapies are preferred by patients, the low permeability of the gastrointestinal tract limits the effectiveness of most compounds, including anticancer drugs. This study proposes the use of a safe sweet cherry extract enriched with polyphenolic compounds as a means to enhance oral absorption. The extract showed high antioxidant capacity, polyphenol content, and anthocyanin content, and it had a favorable safety profile and the ability to improve the permeability of reference compounds. These results suggest that sweet cherry extract may have potential as a permeation enhancer for oral antitumor therapies.
Article
Microbiology
Carla Bromuro, Brunella Posteraro, Rita Murri, Massimo Fantoni, Mario Tumbarello, Maurizio Sanguinetti, Rosanna Dattilo, Roberto Cauda, Antonio Cassone, Antonella Torosantucci, Floyd L. Wormley
Summary: In this retrospective study, antibody immunity in candidemia patients was evaluated by analyzing sera taken at candidemia diagnosis. The presence of IgG antibodies against Candida antigens Als3, Mp65, Hyr1, and Eno1 were observed in all patients at significantly higher levels compared to non-candidemia controls. Antibodies against Als3 and Mp65 were found to be associated with lower 30-day patient mortality. Multivariable logistic regression analysis showed that the antibody response against Als3 and Mp65, along with other variables, could accurately predict candidemia outcome.
Review
Infectious Diseases
Allison M. Hitchcock, Wesley D. Kufel, Keri A. Mastro Dwyer, Eric F. Sidman
Summary: Lenacapavir is a novel HIV-1 treatment option for patients with multidrug-resistant (MDR) HIV-1 infection. It has a favorable pharmacokinetic profile and has shown good tolerability and efficacy in clinical trials.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2024)
Article
Infectious Diseases
Roberta Gagliardini, Alessandro Tavelli, Stefano Rusconi, Sergio Lo Caputo, Vincenzo Spagnuolo, Maria Mercedes Santoro, Andrea Costantini, Alessandra Vergori, Franco Maggiolo, Andrea Giacomelli, Giulia Burastero, Giordano Madeddu, Eugenia Quiros Roldan, Antonella d'Arminio Monforte, Andrea Antinori, Alessandro Cozzi-Lepri
Summary: This study evaluated multiple treatment failures to modern antiretroviral therapy in HIV-infected individuals and found that approximately 4% of them were difficult to treat. The difficult to treat group, compared to the non-difficult to treat group, was characterized by older age, higher prevalence of AIDS, lower CD4+ cell count, and higher risk of treatment failure.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2024)
