Review
Chemistry, Medicinal
Paulo Fernando da Silva Santos-Junior, Martine Schmitt, Joao Xavier de Araujo-Junior, Edeildo Ferreira da Silva-Junior
Summary: Trypanosomatidae family consists of obligatory parasites that affect plants and all classes of vertebrates, especially humans and insects. Inefficient pharmacotherapy justifies the need to discover new drugs to effectively treat diseases caused by these parasites. Targeting sterol 14 alpha-demethylase (CYP51) in Trypanosomatidae parasites shows promising results in developing new bioactive compounds.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Emir Guzel, Ulviye Acar Cevik, Asaf Evrim Evren, Hayrani Eren Bostanci, Ulkuye Dudu Gul, Ugur Kayis, Yusuf Ozkay, Zafer Asim Kaplancikli
Summary: In this study, a series of benzimidazole-1,2,4-triazole derivatives were synthesized and evaluated for their antifungal activity. The compounds showed significant antifungal potential, especially against C. glabrata. Three compounds demonstrated higher antifungal activity compared to voriconazole and fluconazole. Molecular docking studies provided insights into the possible binding mode of these compounds.
Article
Biochemistry & Molecular Biology
David C. Lamb, Tatiana Y. Hargrove, Bin Zhao, Zdzislaw Wawrzak, Jared Goldstone, William David Nes, Steven L. Kelly, Michael R. Waterman, John J. Stegeman, Galina Lepesheva
Summary: Sterol biosynthesis in Methylococcus capsulatus involves a simplified pathway with the key step of sterol 14 alpha-demethylation catalyzed by CYP51. The structure of CYP51fx from M. capsulatus is the first of a bacterial sterol biosynthetic enzyme, suggesting a common evolutionary origin of eukaryotic and bacterial CYP51s. Bioinformatic analysis reveals the presence of CYP51 genes in over 1,000 bacteria, supporting the idea that early eukaryotes may have recruited CYP51 from bacterial sources.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Biochemistry & Molecular Biology
Lu Liu, Hongsu Wang, Li Lin, Yawen Gao, Xiaodi Niu
Summary: The natural compound mulberrin (MBN) has been discovered to effectively inhibit the growth of Botrytis cinerea and prolong the preservation of strawberries. MBN exerts its antifungal activity by inhibiting the activity of 14α-demethylase (CYP51), and its 2-methylpent-2-ene moiety at atom C9 forms a strong pi-cation interaction with the Fe ion of heme in CYP51, making it a critical pharmacophore for CYP51 inhibitors.
Article
Biochemistry & Molecular Biology
Alka Khichi, Ritu Jakhar, Sweety Dahiya, Jasmine Arya, Mehak Dangi, Anil Kumar Chhillar
Summary: Extensive research is necessary to develop new therapeutic strategies for fighting against aggressive fungal infections. This study generated and evaluated analogues of Fluconazole (FLZ) to identify compounds with better potency against fungal-borne infections. Two analogues, 6f and 8f, showed potential for further evaluation based on their molecular docking scores and exhibited low antifungal activities compared to FLZ.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Microbiology
Brian C. Monk, Mikhail Keniya
Summary: Antifungal drugs and agrochemicals are limited by unintended consequences and resistance, highlighting the need for improvement and discovery of novel antifungals. Structural insights into drug targets offer opportunities for more effective antifungal discovery.
Article
Biochemistry & Molecular Biology
Iza Ogris, Urska Zelenko, Izidor Sosic, Martina Gobec, Cene Skubic, Marija Ivanov, Marina Sokovic, Darko Kocjan, Damjana Rozman, Simona Golic Grdadolnik
Summary: This study focused on the main drug target for fungal infections, Sterol 14 alpha-demethylase (CYP51), and developed highly selective inhibitors, offering novel directions for the development of anti-fungal drugs.
BIOORGANIC CHEMISTRY
(2021)
Article
Microbiology
Mariana Handelman, Zohar Meir, Jennifer Scott, Yona Shadkchan, Wei Liu, Ronen Ben-Ami, Jorge Amich, Nir Osherov
Summary: This study revealed that overexpression or mutation of Cyp51B can lead to triazole resistance in Aspergillus fumigatus, suggesting that cyp51B mutations may be a factor in the development of resistance in the fungus.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Chemistry, Organic
Luke R. Churchman, Lauren J. Salisbury, James J. De Voss
Summary: This study reports the first chemical synthesis of the final endogenous substrate of the sterol 14 alpha-demethylases (CYP51s), obtusifoliol, and demonstrates the potential for further investigation into the derivatisation of the sterol skeleton and the development of CYP51 inhibitors to overcome azole resistance in antifungal agents.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Review
Microbiology
Katharina Rosam, Brian C. Monk, Michaela Lackner
Summary: The fungal cytochrome P450 enzyme sterol 14 alpha-demethylase (SDM) is a crucial enzyme in the ergosterol biosynthesis pathway. Binding of azoles to SDM can lead to resistance, affecting treatment efficacy and agricultural productivity.
Article
Biochemistry & Molecular Biology
Surya K. K. De
Summary: Oteseconazole, approved by the US FDA in April 2022, is the first selective and orally bioavailable CYP51 inhibitor for treating patients with recurrent Vulvovaginal candidiasis. This article describes its dosage, administration, chemical structure, physical properties, synthesis, mechanism of action, and pharmacokinetics.
CURRENT MEDICINAL CHEMISTRY
(2023)
Article
Microbiology
Yasmeen N. Ruma, Mikhail V. Keniya, Joel D. A. Tyndall, Brian C. Monk
Summary: The study characterized the wild type C. parapsilosis CYP51 and its resistance-causing point mutation Y132F, revealing increased resistance to fluconazole and voriconazole with the Y132F mutation. The research provides insights into the susceptibility of recombinant CYP51 from C. parapsilosis to azole drugs, which may help advance structure-directed antifungal discovery.
Article
Pharmacology & Pharmacy
Gonzalo Visbal, Rodrigo M. S. Justo, Gabrielle dos Santos da Silva e Miranda, Sara Teixeira de Macedo Silva, Wanderley de Souza, Juliany Cola Fernandes Rodrigues, Maribel Navarro
Summary: In this study, a new complex called ZnCl2(H3)(2) was synthesized and evaluated for its efficacy against Leishmania amazonensis. The results showed that this complex exhibited stronger inhibitory effects on the parasite compared to the free ligand H3. Furthermore, it demonstrated higher selectivity. Additionally, the study revealed that H3 could induce depletion of endogenous parasite sterols and their replacement by 24-desalkyl sterols, and the zinc derivative of H3 resulted in a loss of cell viability.
Article
Biochemistry & Molecular Biology
Luciana S. Paradela, Richard J. Wall, Sandra Carvalho, Giulia Chemi, Victoriano Corpas-Lopez, Eoin Moynihan, Davide Bello, Stephen Patterson, Maria Lucia S. Guther, Alan H. Fairlamb, Michael A. J. Ferguson, Fabio Zuccotto, Julio Martin, Ian H. Gilbert, Susan Wyllie
Summary: A benzothiophene compound with activity against Leishmania donovani was found, with oxidosqualene cyclase (OSC) identified as its target. The amplification of the OSC gene was associated with resistance to the compound, and introduction of an ectopic copy of the gene reduced susceptibility. Biochemical analyses showed substrate accumulation and product depletion in cells treated with the compound, confirming direct binding of the compound to OSC.
CELL CHEMICAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kok Tong Wong, Hasnah Osman, Thaigarajan Parumasivam, Unang Supratman, Mohammad Tasyriq Che Omar, Mohamad Nurul Azmi
Summary: Fourteen pyrazoline derivatives were synthesized through cyclo-condensation reactions, with compound 4a showing the most potent inhibitory activity with a MIC value of 17 μM. Six other synthesized compounds exhibited moderate activity, with MIC ranges between 60 μM to 140 μM. Compound 4a also showed good bactericidal activity, with a MBC value of 34 μM against Mycobacterium tuberculosis H37Ra.
Article
Chemistry, Multidisciplinary
Giulia Anderluzzi, Gustavo Lou, Stuart Woods, Signe Tandrup Schmidt, Simona Gallorini, Michela Brazzoli, Russell Johnson, Craig W. Roberts, Derek T. O'Hagan, Barbara C. Baudner, Yvonne Perrie
Summary: The efficacy of self-amplifying RNA vaccines is influenced by the delivery route and system format. Intramuscular or intradermal administration of the vaccine initially results in comparable immunogenicity, but ionizable lipid nanoparticles generate higher and long-lasting IgG responses. In contrast, intranasal administration leads to low immune responses and rapid clearance at the administration site.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Pharmacology & Pharmacy
Jitkasem Meewan, Sukrut Somani, Partha Laskar, Craig Irving, Margaret Mullin, Stuart Woods, Craig W. Roberts, Abdullah R. Alzahrani, Valerie A. Ferro, Suzanne McGill, Stefan Weidt, Richard Burchmore, Christine Dufes
Summary: The protein corona formed on the nanoparticle surface has a strong influence on cell interactions and uptake of nanomedicines. This study shows that the protein corona affects the uptake of PEGylated zein micelles by cancer cells, macrophages, and dendritic cells. PEGylation gives stealth effects to the zein micelles and makes them promising drug delivery systems for cancer therapy.
Article
Microbiology
Jillian E. Milanes, Jimmy Suryadi, Neil P. Monaghan, Elijah M. Harding, Corbin S. Morris, Soren D. Rozema, Muhammad M. Khalifa, Jennifer E. Golden, Isabelle Q. Phan, Rachael Zigweid, Jan Abendroth, Christopher A. Rice, Hayden T. McCord, Stevin Wilson, Michael K. Fenwick, James C. Morris
Summary: Infection with pathogenic free-living amoebae can cause life-threatening diseases, especially involving the central nervous system. Previous studies have identified the differences in glucokinase enzymes between different amoebae species, highlighting the challenges in developing broad-spectrum amoebic inhibitors.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
International Relations
Anishka Cameron, Regina Esiovwa, John Connolly, Andrew Hursthouse, Fiona Henriquez
Summary: The global COVID-19 pandemic has worsened existing health, social, and economic challenges and posed a threat to achieving the UN sustainable development goals. In this article, we discuss the lessons learned from the pandemic for global health security governance, focusing on antimicrobial resistance. We emphasize the importance of the One Health approach, which involves collaboration across disciplines and sectors to better understand the complex interactions between humans, animals, and the environment. However, we also highlight the need for greater representation of the environmental sector in One Health networks and the significance of incorporating social sciences and effective communication in health security research.
Article
Biochemistry & Molecular Biology
Kristof B. Cank, Robert A. Shepherd, Sonja L. Knowles, Manuel Rangel-Grimaldo, Huzefa A. Raja, Zoie L. Bunch, Nadja B. Cech, Christopher A. Rice, Dennis E. Kyle, Joseph O. Falkinham, Joanna E. Burdette, Nicholas H. Oberlies
Summary: Studies on an organic extract of marine fungus Periconia sp. led to the discovery of three rare halogenated cyclopentenes. The structures and configurations of these compounds were determined using various analytical techniques. The compounds were found to be inactive in the tested activities.
Article
Infectious Diseases
Binod Rayamajhee, Savitri Sharma, Mark Willcox, Fiona L. Henriquez, Raksheeth Nathan Rajagopal, Gauri Shankar Shrestha, Dinesh Subedi, Bhupesh Bagga, Nicole Carnt
Summary: This study aimed to examine the Acanthamoeba species and genotypes recovered from patients with Acanthamoeba keratitis, determine the presence of endosymbionts in ocular isolates of Acanthamoeba, and review the clinical presentations.
BMC INFECTIOUS DISEASES
(2022)
Review
Parasitology
Binod Rayamajhee, Mark D. P. Willcox, Fiona L. Henriquez, Constantinos Petsoglou, Dinesh Subedi, Nicole Carnt
Summary: This paper reviews the characteristics of Acanthamoeba as an emerging human pathogen and its relationship with other microbes, revealing their importance in the evolution, persistence, and transmission of potential human pathogens.
TRENDS IN PARASITOLOGY
(2022)
Article
Dentistry, Oral Surgery & Medicine
Krystyna Piela, Paddy Watson, Reuben Donnelly, Marilyn Goulding, Fiona L. Henriquez, William MacKay, Shauna Culshaw
Summary: This study assessed the effectiveness of various intra-oral suction devices in mitigating dental aerosols. It found that high-volume dynamic suction devices effectively eliminated aerosol particle escape from the oral cavity, while static devices allowed periodic escape of particles.
Article
Agriculture, Dairy & Animal Science
M. Jones, M. E. Alexander, S. Lightbody, D. Snellgrove, P. Smith, S. Bramhall, F. L. Henriquez, I. McLellan, K. A. Sloman
Summary: Ornamental fishes can experience compromised welfare during the transportation process, but post-transport tank composition and visual cues can improve their behavior and welfare. Fish placed in tanks with conspecifics exhibited more aggression and had shorter latency to forage.
APPLIED ANIMAL BEHAVIOUR SCIENCE
(2023)
Article
Parasitology
Somayeh Bahrami, Zeinab Asadi, Mehdi Zarei, Hossein Hamidinejat, Fiona L. Henriquez
Summary: In this study, the cytopathic and phagocytic properties of Acanthamoeba castellanii trophozoites were examined after exposure to sublethal concentrations of chlorine. Results showed that chlorine-treated trophozoites exhibited more extensive cytopathic effects, higher bacterial uptake rate, and increased antioxidant enzyme activities compared to untreated cells. mRNA expression analysis revealed upregulation of virulence genes in chlorine-treated trophozoites. Proper concentration and exposure time of chlorine are crucial to prevent the development of resistance and virulent amoebae.
PARASITOLOGY RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Ana C. Zanatta, Natalia Carolina Vieira, Renato Dantas-Medeiros, Wagner Vilegas, RuAngelie Edrada-Ebel
Summary: This study analyzed the chemical composition of Terminalia catappa L. plant extracts using LC-MS and NMR data analysis techniques. It identified 90 compounds, including triterpenes and C-glycosyl flavones, which significantly contributed to differences between autumn/winter and spring samples. The variations in compound composition of the plant leaves may be due to environmental stress and leaf development.
Article
Plant Sciences
Dana Atoum, Ignacio Fernandez-Pastor, Louise Young, RuAngelie Edrada-Ebel
Summary: This study compared the metabolomic profile and biological activity of Jordanian and European chamomile grown under different environmental conditions. European chamomile exhibited anticancer and antioxidant activity, while Jordanian chamomile only showed antioxidant activity. Both chamomile varieties contained dicaffeoylquinic acid isomers with antioxidant capability. Additionally, European chamomile contained chrysosplenetin and apigenin, which displayed anticancer activity.
Editorial Material
Veterinary Sciences
Elisabetta Antuofermo, Marta Polinas, Daniele Dessi, Fiona Luisa Henriquez
FRONTIERS IN VETERINARY SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Bianca Goncalves Vasconcelos de Alcantara, Albert Katchborian Neto, Daniela Aparecida Garcia, Rosana Casoti, Tiago Branquinho Oliveira, Ana Claudia Chagas de Paula Ladvocat, Ruangelie Edrada-Ebel, Marisi Gomes Soares, Danielle Ferreira Dias, Daniela Aparecida Chagas de Paula
Summary: This study aimed to screen the anti-inflammatory activity of the Lauraceae plant family and build statistical prediction models. Ex vivo results showed significant anti-inflammatory activity for some plants, and prediction models using metabolomics data were validated for predicting active extracts and studying bioactive metabolites.
CHEMISTRY & BIODIVERSITY
(2023)
Article
Microbiology
Kevin Jace Miranda, Saif Jaber, Dana Atoum, Subha Arjunan, Rainer Ebel, Marcel Jaspars, Ruangelie Edrada-Ebel
Summary: Genome mining and metabolomics are valuable tools in natural products research. In this study, a new compound called pseudomonassin was isolated from a deep-sea organism using a co-cultivation approach. Metabolomics analysis revealed other potential metabolites.