Article
Pharmacology & Pharmacy
Palang Chotsiri, Almahamoudou Mahamar, Richard M. Hoglund, Fanta Koita, Koualy Sanogo, Halimatou Diawara, Alassane Dicko, Julie A. Simpson, Teun Bousema, Nicholas J. White, Joelle M. Brown, Roly Gosling, Ingrid Chen, Joel Tarning
Summary: Clinical studies have shown that adding a single dose of primaquine to antimalarial regimens can rapidly eliminate Plasmodium falciparum gametocytes. However, the mechanism and impact on malaria transmission remain unclear. This study used data from Malian adults with gametocytemia to investigate the pharmacokinetic-pharmacodynamic relationships of primaquine's transmission blocking activity. It was found that a low dose of primaquine can effectively prevent the transmission of P. falciparum.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Immunology
Janette Reader, Mariette E. van der Watt, Lyn-Marie Birkholtz
Summary: This study optimized a simple and cost-effective strategy for describing the stage-specific action of antimalarial compounds against different developmental stages of the malaria parasite.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Flore Nardella, Irina Dobrescu, Haitham Hassan, Fabien Rodrigues, Sabine Thiberge, Liliana Mancio-Silva, Ambre Tafit, Corinne Jallet, Veronique Cadet-Daniel, Stephane Goussin, Audrey Lorthiois, Yoann Menon, Nicolas Molinier, Dany Pechalrieu, Christophe Long, Francois Sautel, Mariette Matondo, Magalie Duchateau, Guillaume Medard, Benoit Witkowski, Artur Scherf, Ludovic Halby, Paola B. Arimondo
Summary: Malaria eradication requires the development of new drugs to combat drug-resistant parasites. Bisbenzylisoquinoline alkaloids isolated from Cocculus hirsutus were found to be active against Plasmodium falciparum blood stages. Compound 125, a derivative of these alkaloids, showed significantly improved preclinical properties and demonstrated effectiveness against drug-resistant clinical isolates and malaria transmission stages.
Article
Infectious Diseases
Gustavo J. C. Freitas, Noelly Q. Ribeiro, Ludmila Gouveia-Eufrasio, Eluzia C. P. Emidio, Gabriele M. Guimaraes, Isabela C. Cesar, Tatiane A. Paixao, Jeferson B. S. Oliveira, Melissa Caza, James W. Kronstad, Daniel A. Santos
Summary: Cryptococcus gattii and Cryptococcus neoformans are the main causes of cryptococcosis, and the current treatments for this invasive fungal infection, such as amphotericin B, 5-fluorocytosine, and fluconazole, have limitations including toxicity and antifungal resistance. This study investigated the repurposing of antimalarial drugs (ATMs) for cryptococcosis treatment and found that ATMs not only inhibited fungal growth but also induced oxidative and nitrosative stresses, and altered fungal physiology. ATMs showed synergistic effects when combined with amphotericin B, reducing its fungicidal concentrations and toxicity to macrophages. Furthermore, the combination of halofantrine or amodiaquine with amphotericin B effectively reduced the lethality and fungal burden in murine cryptococcosis. These findings provide new perspectives for the use of ATMs against cryptococcosis and other fungal infections.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Microbiology
Henriette Bosson-Vanga, Nicolas Primas, Jean-Francois Franetich, Catherine Lavazec, Lina Gomez, Kutub Ashraf, Maurel Tefit, Valerie Soulard, Nathalie Dereuddre-Bosquet, Roger Le Grand, Melanie Donnette, Romain Mustiere, Nadia Amanzougaghene, Shahin Tajeri, Peggy Suzanne, Aurelie Malzert-Freon, Sylvain Rault, Patrice Vanelle, Sebastien Hutter, Anita Cohen, Georges Snounou, Pierre Roques, Nadine Azas, Prisca Lagardere, Vincent Lisowski, Nicolas Masurier, Michel Nguyen, Lucie Paloque, Francoise Benoit-Vical, Pierre Verhaeghe, Dominique Mazier
Summary: This study presents a new chemical structure that is active against multiple stages of the human malaria parasite, including those resistant to artemisinins. The molecule also reduces transmission of the parasite to the mosquito vector in a mouse model. This new compound family shows promise for the development of novel antimalarial drugs with a unique multi-stage mechanism of action.
MICROBIOLOGY SPECTRUM
(2021)
Article
Public, Environmental & Occupational Health
Stephane Picot, Frederic Beugnet, Gilles Leboucher, Anne-Lise Bienvenu
Summary: Antimicrobials, including antibiotics, antiparasitic, and antifungals, are facing resistance, calling for a comprehensive approach to counteract the issue, especially in the context of the COVID-19 pandemic that may exacerbate antimicrobial resistance.
Article
Chemistry, Medicinal
Jandeli Niemand, Riette van Biljon, Mariette van der Watt, Ashleigh van Heerden, Janette Reader, Roelof van Wyk, Lindsey Orchard, Kelly Chibale, Manuel Llinas, Lyn-Marie Birkholtz
Summary: The study reveals differential activity of kinase inhibitors against different stages of Plasmodium falciparum gametocytes through transcriptome fingerprinting, highlighting the importance of targeting late-stage gametocytes for the development of transmission-blocking antimalarials.
ACS INFECTIOUS DISEASES
(2021)
Article
Engineering, Biomedical
Tomislav Roncevic, Marco Gerdol, Mario Mardirossian, Matko Males, Svjetlana Cvjetan, Monica Benincasa, Ana Maravic, Goran Gajski, Lucija Krce, Ivica Aviani, Jerko Hrabar, Zeljka Trumbic, Maik Derks, Alberto Pallavicini, Markus Weingarth, Larisa Zoranic, Alessandro Tossi, Ivona Mladineo
Summary: This study reveals the important role of antimicrobial peptides in the survival of the marine parasite Anisakis and elucidates their mechanism of action against bacterial infections. These peptides exhibit potent bactericidal activity against Gram-negative bacteria, including multi-drug resistant strains, making them promising candidates for further drug development.
ACTA BIOMATERIALIA
(2022)
Review
Chemistry, Medicinal
Santosh Kumar Verma, Rameshwari Verma, Kothanahally S. Sharath Kumar, Laxmi Banjare, Afzal B. Shaik, Richie R. Bhandare, Kadalipura P. Rakesh, Kanchugarakoppal S. Rangappa
Summary: MRSA is becoming a major concern due to its rapid resistance development, prompting the need for novel antibiotics. The oxadiazole moiety serves as an interesting and adaptable molecular structure with potential for research and development as antibacterial agents. Studies on oxadiazole-containing derivatives as potent antibacterial agents against multidrug-resistant MRSA strains and exploring structure-activity relationships have been conducted, providing valuable insights for future drug development.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Microbiology
Kaira C. P. Tomaz, Tatyana A. Tavella, Joyce V. B. Borba, Luis C. Salazar-Alvarez, Joao E. Levandoski, Melina Mottin, Bruna K. P. Sousa, Jose T. Moreira-Filho, Vitor M. Almeida, Leandro C. Clementino, Catarina Bourgard, Katlin B. Massirer, Rafael M. Counago, Carolina H. Andrade, Per Sunnerhagen, Elizabeth Bilsland, Gustavo C. Cassiano, Fabio T. M. Costa
Summary: Drug resistance is a major challenge in malaria control, and this study discovered a new potential antimalarial compound through computational chemistry methods. The compound showed strong activity against asexual blood-stage parasites. Furthermore, the study found that the compound inhibited specific protein kinases in yeast through chemical-genetic interaction analysis. These findings suggest that the compound has the potential to be a drug target for multi-stage antimalarials.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Biotechnology & Applied Microbiology
Haomin Wu, Pengfei Xu, Ya Huang, Liping Wang, Xinyue Ye, Xiaowei Huang, Lingman Ma, ChangLin Zhou
Summary: Novel antimicrobial peptides were designed and characterized, with hybrid peptides PCL-1 and Pb2-1TI showing superior broad-spectrum antimicrobial activity compared to the original peptide Pb2-1. PCL-1 exhibited lower cytotoxicity and high stability, making it a promising candidate for clinical treatment of bacterial infections.
PROBIOTICS AND ANTIMICROBIAL PROTEINS
(2021)
Article
Chemistry, Physical
Sarra Riahi, Nizar Ben Moussa, Mohamed Lajnef, Nessrine Jebari, Ali Dabek, Radhouane Chtourou, Gregory Guisbiers, Sophie Vimont, Etienne Herth
Summary: Due to the excessive use of antibiotics in agriculture, bacteria have developed resistance, leading to the global spread of Antibiotic Resistant Bacteria and causing hundreds of thousands of deaths. This paper proposes the use of zinc oxide nanoparticles synthesized by a sol-gel technique as a potential solution against various types of bacteria, including Gram-negative, Gram-positive, and multidrug-resistant strains. The study determined the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), and found that the zinc oxide nanoparticles were effective against several bacteria strains, including Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Article
Chemistry, Medicinal
Preeti Singh, Chiranjeev Sharma, Bhawana Sharma, Anupam Mishra, Drishti Agarwal, Deepika Kannan, Jana Held, Shailja Singh, Satish K. Awasthi
Summary: This study reports a rapid method for synthesizing N-sulfonylpiperidine dispiro-1,2,4,5-tetraoxane analogs for antimalarial research. The synthesized compounds were characterized and evaluated for their in vitro and in vivo antimalarial activities.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Plant Sciences
De-Li Chen, Mei-Ying Chen, Yong Hou, Can-Hong Wang, Zhao-Cui Sun, Yun Yang, Han-Qiao Liang, Guo-Xu Ma, Xu-Dong Xu, Jian-He Wei
Summary: Eight new cadinane sesquiterpenoids, along with two known compounds, were isolated from infected stems of Hibiscus tiliaceus. The structures of the compounds were elucidated through NMR, MS, and crystallography, and their cytotoxic activities against HepG2 and Huh7 cell lines were evaluated. Compounds 1b, 2b, 4, 6, and 8 showed significant cytotoxicity towards both cell lines.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Biochemistry & Molecular Biology
Jeyce Kelle Ferreira de Andrade, Alexandre Jose da Silva Goes, Vanessa Xavier Barbosa, Mariza Severina de Lima Silva, Mariana Aragao Matos Donato, Christina Alves Peixoto, Gardenia Carmen Gadelha Militao, Teresinha Goncalves da Silva
Summary: Thiosemicarbazones derived from beta-lapachone showed potent cytotoxic effects on leukemia cells, with BV3 being the most selective compound, exhibiting high toxicity to tumor cells and low toxicity to normal cells. These compounds have the potential to be promising candidates for anticancer drugs.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Chemistry, Multidisciplinary
Beatrice Jia Min Ng, Jia Yi Han, Yongbeom Kim, Kenzo Aki Togo, Jia Ying Chew, Yulin Lam, Fun Man Fung
Summary: Teaching and learning faced greater challenges during the COVID-19 pandemic, but using online collaborative platforms can enhance student-student and student-teacher interactions, increasing social and learning presence.
JOURNAL OF CHEMICAL EDUCATION
(2022)
Article
Microbiology
Francesca Sisto, Simone Carradori, Sarah D'Alessandro, Nadia Santo, Norma Lattuada, Richard K. Haynes, Donatella Taramelli, Rossella Grande
Summary: This study evaluated the in vitro activity of arylaminoartemisinin GC012 against clinical strains of H. pylori with different antibiotic susceptibilities. GC012 showed significantly lower MIC and MBC values compared to DHA, indicating its potential as an effective treatment for H. pylori infection. Combination of GC012 with metronidazole, clarithromycin, and amoxicillin displayed synergistic interactions. Additionally, GC012 inhibited biofilm formation and showed minimal biofilm eradication concentration (MBEC) on mature biofilm. Structural changes in the bacterial membrane were observed for both GC012 and DHA.
Article
Pharmacology & Pharmacy
J. W. Bezuidenhout, M. Aucamp, N. Stieger, W. Liebenberg, R. K. Haynes
Summary: To establish the best processing parameters and storage conditions for nanolipid formulations of artesunate, the thermal stability and solubility profiles of artesunate in aqueous solutions were evaluated at different temperatures and pH levels. The study found that artesunate remained relatively stable at temperatures up to 40°C and 75% relative humidity for 3 months, with approximately 9% decomposition. However, higher temperatures led to significantly greater decomposition and the formation of dihydroartemisinin (DHA) and other products. The solubility of artesunate varied with pH, with the highest solubility observed at pH 6.8 (phosphate buffer). Overall, maintaining relatively low temperatures is crucial for the preparation and storage of artesunate formulations.
Article
Biochemistry & Molecular Biology
Giovanni Ribaudo, Xiaoyun Yun, Alberto Ongaro, Erika Oselladore, Jerome P. L. Ng, Richard K. Haynes, Betty Yuen Kwan Law, Maurizio Memo, Vincent Kam Wai Wong, Paolo Coghi, Alessandra Gianoncelli
Summary: By utilizing computational tools, this study identified two potential antimalarial drugs, amodiaquine and methylene blue, as possible PLpro inhibitors. These findings provide a starting point for the development of new PLpro inhibitors.
CHEMICAL BIOLOGY & DRUG DESIGN
(2023)
Review
Plant Sciences
Barend Jacobus Lee, Morne Weyers, Richard Kingston Haynes, Frank van der Kooy
Summary: This article reviews the history of the discovery of artemisinin and the development of combination therapies, as well as the current production techniques and the possibility of producing artemisinin in South Africa. Although artemisinin and its derivatives are widely used for malaria treatment worldwide, the supply is insufficient, especially when used for other diseases. To meet the demand, higher yielding cultivars and novel extraction and purification techniques are needed.
SOUTH AFRICAN JOURNAL OF BOTANY
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Hannes Leupe, Stephen Ahenkorah, Jeroen Dekervel, Marcus Unterrainer, Eric Van Cutsem, Chris Verslype, Frederik Cleeren, Christophe M. Deroose
Summary: Molecular imaging of somatostatin receptors is crucial in the clinical management of neuroendocrine tumors. PET imaging with 68Ga or 64Cu labeled somatostatin analogs is currently the gold standard, but practical and economic issues hinder widespread implementation of 68Ga imaging. Recent advancements in radiochemistry have enabled the use of 18F labeling, leading to promising clinical translations of 18F-labeled somatostatin analogs. This review presents updated clinical data and justifies the clinical application of these tracers.
JOURNAL OF NUCLEAR MEDICINE
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Stephen Ahenkorah, Christopher Cawthorne, Erika Murce, Christophe M. Deroose, Thomas Cardinaels, Yann Seimbille, Guy Bormans, Maarten Ooms, Frederik Cleeren
Summary: In this study, [18F]AlF-NOTA-JR11 was synthesized and directly compared with [18F]AlF-NOTA-octreotide as SSTR PET probes for neuroendocrine tumor (NET) imaging. The results showed that [18F]AlF-NOTA-JR11 had higher cell binding, but similar pharmacokinetics and tumor uptake compared to [18F]AlF-NOTA-octreotide. Rating: 6/10
NUCLEAR MEDICINE AND BIOLOGY
(2023)
Article
Parasitology
Joachim Mueller, Carling Schlange, Manfred Heller, Anne-Christine Uldry, Sophie Braga-Lagache, Richard K. Haynes, Andrew Hemphill
Summary: Artemisinin and its amino-artemisinin derivatives are potent antimalarials and exhibit different mechanisms of action against Plasmodium and T. gondii. The amino-artemisinins are effective in vitro against non-heme-degrading apicomplexan parasites including T. gondii. However, T. gondii strains readily adapt to increased concentrations of these compounds, resulting in the development of resistant strains.
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2023)
Review
Pharmacology & Pharmacy
Danielle van Staden, Richard K. K. Haynes, Joe M. M. Viljoen
Summary: Self-emulsification is a formulation technique that improves oral drug delivery by enhancing solubility and bioavailability. It provides a simplified method for delivering lipophilic drugs by producing emulsions upon moderate agitation and dilution. It is also a promising approach for topical drug delivery, offering simplified production procedures and unlimited upscaling possibilities.
Article
Microbiology
Jessica Ramseier, Dennis Imhof, Kai Pascal Alexander Haenggeli, Nicoleta Anghel, Ghalia Boubaker, Richard M. Beteck, Luis-Miguel Ortega-Mora, Richard K. K. Haynes, Andrew Hemphill
Summary: The effects of decoquinate and three O-quinoline-carbamate-derivatives were investigated on human foreskin fibroblasts infected with Neospora caninum tachyzoites. These compounds exhibited different levels of proliferation inhibition and did not affect cell viability at certain concentrations. Treatment with lower concentrations altered the ultrastructure of the parasite, while long-term treatment with one compound showed parasiticidal effects. These compounds were then tested in a murine model, but did not show activity against neosporosis.
Article
Chemistry, Medicinal
Erika Murce, Stephen Ahenkorah, Savanne Beekman, Maryana Handula, Debra Stuurman, Corrina de Ridder, Frederik Cleeren, Yann Seimbille
Summary: In this study, 3p-C-NETA-ePSMA-16 was synthesized and showed high affinity to PSMA, as well as specific uptake in PSMA expressing cells and tumors. It also exhibited improved tumor visualization and imaging contrast compared to other radiopharmaceuticals. Furthermore, 3p-C-NETA-ePSMA-16 has potential for radiotherapy.
Article
Chemistry, Medicinal
Danielle van Staden, Richard K. Haynes, Joe M. Viljoen
Summary: Self-emulsifying drug delivery systems (SEDDSs) are lipid-based systems that provide superior drug protection and control over drug concentration profiles, making them a promising option for oral drug delivery. Dermal spontaneous emulsions have also gained interest due to their ability to deliver drugs across mucus membranes and skin layers.
Review
Chemistry, Medicinal
Lorencia Taljaard, Richard K. Haynes, Frank van der Kooy
Summary: Schistosomiasis, a neglected tropical disease, can be controlled and ultimately eliminated by reducing snail populations and preventing and treating schistosomiasis infections. Novel antischistosomal drugs are needed to address concerns about drug resistance, and the genus Artemisia shows promise due to its effects on both schistosomes and snail vectors. The combination of artemisinin and praziquantel presents a potential treatment option for schistosomiasis.
REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY
(2023)
Meeting Abstract
Radiology, Nuclear Medicine & Medical Imaging
Stephen Ahenkorah, Danni Ramdhani, Christophe Deroose, Thomas Cardinaels, Guy Bormans, Frederik Cleeren, Maarten Ooms
NUCLEAR MEDICINE AND BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Kevin Timothy Fridianto, Gregory Adrian Gunawan, Kiel Hards, Jickky Palmae Sarathy, Gregory M. Cook, Thomas Dick, Mei-Lin Go, Yulin Lam
Summary: In this study, we demonstrated the switch of the compound's mode-of-action by relocating the positive charge, while maintaining its excellent antibacterial activity and selectivity. Through rapid bacterial membrane depolarization, the compound achieved bactericidal activity in the low micromolar range, depleting intracellular ATP.
RSC MEDICINAL CHEMISTRY
(2022)
