Article
Chemistry, Medicinal
Benjamin R. Taft, Fumiaki Yokokawa, Tom Kirrane, Anne-Catherine Mata, Richard Huang, Nicole Blaquiere, Grace Waldron, Bin Zou, Oliver Simon, Subramanyam Vankadara, Wai Ling Chan, Mei Ding, Sandra Sim, Judith Straimer, Armand Guiguemde, Suresh B. Lakshminarayana, Jay Prakash Jain, Christophe Bodenreider, Christopher Thompson, Christian Lanshoeft, Wei Shu, Eric Fang, Jafri Qumber, Katherine Chan, Luying Pei, Yen-Liang Chen, Hanna Schulz, Jessie Lim, Siti Nurdiana Abas, Xiaoman Ang, Yugang Liu, Inigo Angulo-Barturen, Maria Belen Jimenez-Diaz, Francisco Javier Gamo, Benigno Crespo-Fernandez, Philip J. Rosenthal, Roland A. Cooper, Patrick Tumwebaze, Anna Caroline Campos Aguiar, Brice Campo, Simon Campbell, Jurgen Wagner, Thierry T. Diagana, Christopher Sarko
Summary: A highly potent antimalarial compound, INE963 (1), with favorable pharmacological properties, has been identified through high-throughput screening and shows potential for curing uncomplicated malaria.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Carolina Herrera, Mackenzie L. Cottrell, John Prybylski, Angela D. M. Kashuba, Ronald S. Veazey, Javier Garcia-Perez, Natalia Olejniczak, Clare F. McCoy, Paul Ziprin, Nicola Richardson-Harman, Jose Alcami, Karl R. Malcolm, Robin J. Shattock
Summary: The utility of non-human primates in evaluating antiretroviral drugs for HIV treatment and prevention is questionable due to pharmacological differences between humans and macaques. We developed an ex vivo model using tissue explants to identify differences in drug efficacy between the two species. Our results showed that high concentrations of tenofovir and maraviroc predicted anti-viral efficacy, with greater inhibitory potency observed in macaques compared to humans.
Article
Multidisciplinary Sciences
Tanyaluck Kampoun, Pimpisid Koonyosying, Jetsada Ruangsuriya, Parichat Prommana, Philip J. Shaw, Sumalee Kamchonwongpaisan, Hery Suwito, Ni Nyoman Tri Puspaningsih, Chairat Uthaipibull, Somdet Srichairatanakool
Summary: This study found that the antimalarial compound C3 and iron chelators have similar antimalarial effects and inhibit the action of iron ions on dihydroartemisinin (DHA). The results suggest that drugs with inhibitory effects on the Fd/FNR redox system should be avoided as partner drugs for DHA in combination therapy.
Article
Parasitology
Naoyuki Fukuda, Shin-Ichiro Tachibana, Mie Ikeda, Miki Sakurai-Yatsushiro, Betty Balikagala, Osbert T. Katuro, Masato Yamauchi, Sakurako Emoto, Muneaki Hashimoto, Shouki Yatsushiro, Makoto Sekihara, Toshiyuki Mori, Makoto Hirai, Walter Opio, Paul S. Obwoya, Mary A. Auma, Denis A. Anywar, Masatoshi Kataoka, Nirianne M. Q. Palacpac, Emmanuel Odongo-Aginya, Eisaku Kimura, Martin Ogwang, Toshihiro Horii, Toshihiro Mita
Summary: After the introduction of artemether-lumefantrine in Uganda as a treatment for malaria, a decrease in ex vivo efficacy of lumefantrine and detection of artemisinin-resistant Plasmodium falciparum have been reported. This study suggests that amodiaquine may be a promising alternative to lumefantrine in case of resistance emergence, and reduced sensitivity to mefloquine is associated with the pfcrt K76 wild-type allele. Monitoring of antimalarial susceptibility in Northern Uganda is emphasized for developing appropriate treatment strategies.
PARASITOLOGY INTERNATIONAL
(2021)
Article
Microbiology
Haddijatou Mbye, Fatoumata Bojang, Aminata Seedy Jawara, Bekai Njie, Nuredin Ibrahim Mohammed, Joseph Okebe, Umberto D'Alessandro, Alfred Amambua-Ngwa
Summary: This study used PSRA to detect ex vivo antimalarial tolerance in Gambian P. falciparum, showing faster killing and lower variance after treatment with DHA. Some isolates exhibited tolerance to both DHA and LUM, while those with the PfMDR1-Y184F mutant variant showed increased LUM survival.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Medicine, Research & Experimental
Manreet Kaur, Vanessa Yardley, Ke Wang, Jinit Masania, Randolph R. J. Arroo, David B. Turner, Mingzhong Li
Summary: This study evaluated and predicted the pharmacokinetic performance of artemisinin cocrystal formulations using in vivo murine animal and PBPK models. The cocrystal formulations showed enhanced efficacy compared to the parent drug ART in mice infected with Plasmodium berghei, with lower doses required to achieve therapeutic effects. The PBPK modeling strategy proved to be efficient in predicting the PK parameters of the ART cocrystal formulation based on in vitro and in vivo experimental investigations.
MOLECULAR PHARMACEUTICS
(2021)
Article
Microbiology
Jon Bruss, Troy Lister, Vipul K. Gupta, Emily Stone, Lisa Morelli, Yang Lei, David Melnick
Summary: SPR206, a novel polymyxin derivative, shows potent activity against multidrug-resistant bacteria and demonstrates good safety and tolerability in healthy subjects. Drug exposure and excretion are dose-dependent, with minimal accumulation and no evidence of nephrotoxicity observed.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Infectious Diseases
Soo Min Jang, Lenar Yessayan, Michael Dean, Gabrielle Costello, Ravi Katwaru, Bruce A. Mueller
Summary: The study aimed to determine the adsorption and transmembrane clearances of imipenem and relebactam in CRRT models, using Monte Carlo Simulation for drug dosing recommendations. Results showed that the two drugs were not adsorbed to the CRRT apparatus, but crossed the hemodiafilter membrane effectively. Dosage adjustment may be necessary for critically ill patients receiving CRRT.
Article
Biochemistry & Molecular Biology
Ken Mizuta, Yoshitaka Katou, Baku Nakakita, Aoi Kishine, Yoshiaki Nosaka, Saki Saito, Chizuru Iwatani, Hideaki Tsuchiya, Ikuo Kawamoto, Masataka Nakaya, Tomoyuki Tsukiyama, Masahiro Nagano, Yoji Kojima, Tomonori Nakamura, Yukihiro Yabuta, Akihito Horie, Masaki Mandai, Hiroshi Ohta, Mitinori Saitou
Summary: This study demonstrates the ex vivo reconstitution of fetal oocyte development in humans and monkeys, providing a critical step forward for in vitro oogenesis in humans and uncovering important characteristics of fetal oocyte development in primates. The cytological and transcriptomic progressions of fetal oocyte development in vitro closely recapitulate those in vivo, revealing species-specific and conserved programs driving this process.
Article
Pharmacology & Pharmacy
Mohamed M. Badran, Nadia N. Alouny, Basmah N. Aldosari, Ahlam M. Alhusaini, Amal El Sayeh Abou El Ela
Summary: The study developed a sustained-release transdermal GLP film using chitosan-coated deformable liposomes (DLs) to overcome the challenges associated with oral administration of the drug. The DLs showed improved drug transdermal delivery compared to conventional liposomes (CL), with high stability and deformability. The in vitro release study confirmed sustained release of GLP, and coating with CS further enhanced the sustained release. The transdermal films demonstrated promising pharmacokinetic profiles and higher hypoglycemic effect compared to oral GLP, indicating the potential of systemic action through local topical delivery.
Article
Chemistry, Medicinal
Heloise Cahuzac, Antoine Sallustrau, Carole Malgorn, Fabrice Beau, Peggy Barbe, Victor Babin, Steven Dubois, Alberto Palazzolo, Robert Thai, Isabelle Correia, Ki Baek Lee, Sebastien Garcia-Argote, Olivier Lequin, Mathilde Keck, Herve Nozach, Sophie Feuillastre, Xin Ge, Gregory Pieters, Davide Audisio, Laurent Devel
Summary: This article presents a bioanalytical strategy based on dual radiolabeling and ex vivo digital imaging for accurate determination of the plasma and tissue profiles of protein-drug conjugates. The strategy involves enzymatic and chemical reactions to obtain dual-labeled anti-MMP-14 Fabs conjugated to monomethyl auristatin E, allowing for simultaneous monitoring and accurate quantification of the components during circulation phase and accumulation in different organs.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Microbiology
Martin Okitwi, Stephen Orena, Katairo Thomas, Patrick K. Tumwebaze, Oswald Byaruhanga, Samuel L. Nsobya, Melissa D. Conrad, Brett R. Bayles, Philip J. Rosenthal, Roland A. Cooper
Summary: In this study, susceptibilities of Plasmodium falciparum isolates from Uganda were measured, both on the day of collection and after storage. The findings indicate that short-term storage before drug susceptibility determination is feasible.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Chemistry, Medicinal
Laurent Dembele, Nouhoum Diallo, Fanta Sogore, Bintou Diarra, Fatoumata Ballo, Amadou Daou, Ousmaila Diakite, Yacouba Bare, Cheick Papa Oumar Sangare, Aboubecrin Sedhigh Haidara, Seidina A. S. Diakite, Amadou Niangaly, Mahamadou Diakite, Brice Campo, Gordon A. Awandare, Yaw Aniweh, Abdoulaye A. Djimde
Summary: The absence of an in vitro cultivation system for Plasmodium malariae makes it difficult to evaluate antimalarial drugs targeting its asexual blood stages. Despite the effectiveness of artemisinin combination therapies on P. falciparum, the increasing detection of P. malariae in malaria-endemic countries poses a challenge.
ACS INFECTIOUS DISEASES
(2021)
Article
Infectious Diseases
Yasuhiro Umezaki, Kazuaki Matsumoto, Kazuro Ikawa, Yuta Yokoyama, Yuki Enoki, Akari Shigemi, Erika Watanabe, Koyo Nakamura, Keiichiro Ueno, Hideyuki Terazono, Norifumi Morikawa, Yasuo Takeda
Summary: This study demonstrated that the pharmacokinetic/pharmacodynamic index of pazufloxacin can be used to optimize dosing regimens for P. aeruginosa infection, and a successful PK/PD model was constructed.
Article
Infectious Diseases
Pierre Chauvelot, Celine Dupieux-Chabert, Lelia Abad, Aubin Souche, Tristan Ferry, Jerome Josse, Frederic Laurent, Florent Valour
Summary: The study demonstrated that dalbavancin has the ability to effectively eradicate intraosteoblastic reservoir of Staphylococcus aureus in bone and joint infections. It showed significant reduction in bacterial inoculum at both low concentration and standard therapeutic doses, with similar efficacy to vancomycin but less efficient than rifampicin. Dalbavancin was found to be the only molecule significantly active at a low concentration.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Chemistry, Multidisciplinary
Monalisa Roy, Keyao Li, Madiha Nisar, Lawrence W-Y Wong, Herman H-Y Sung, Richard K. Haynes, Ian D. Williams
Summary: The X-ray structures of three new 1:1 pharmaceutical cocrystals of 11-aza-artemisinin with bromo-substituted salicylic acids are reported, showing variations in their packing arrangements. This study provides insight into the crystal packing efficiency of the cocrystals based on hydrogen bonding interactions.
ACTA CRYSTALLOGRAPHICA SECTION C-STRUCTURAL CHEMISTRY
(2021)
Article
Microbiology
Daniel J. Watson, Lizahn Laing, Liezl Gibhard, Ho Ning Wong, Richard K. Haynes, Lubbe Wiesner
Summary: The article reviews the pharmacokinetic properties of various amino-artemisinins in mice, highlighting their potential as components of triple combination therapies due to favorable efficacy and pharmacokinetics.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
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.
Review
Infectious Diseases
Danielle van Staden, Richard K. Haynes, Joe M. Viljoen
Summary: Despite available chemotherapeutic treatment regimens and efforts to develop new drugs for tuberculosis, the disease remains challenging to treat due to the nature of the causative pathogen and drug resistance. The World Health Organization introduced the End-TB initiative to eliminate tuberculosis, but the COVID-19 pandemic has hindered progress. Therefore, there is a need for enhanced scientific understanding, repurposing of drugs, and new treatment methods. This review focuses on utilizing self-double-emulsifying drug delivery systems for topical treatment of cutaneous tuberculosis and other mycobacterial infections.
Article
Pharmacology & Pharmacy
Daniel J. J. Watson, Lizahn Laing, Richard M. M. Beteck, Liezl Gibhard, Richard K. K. Haynes, Lubbe Wiesner
Summary: The emergence of drug-resistant malaria strains has necessitated the development of new combination therapies. In this study, the pharmacokinetics of decoquinate and its derivatives were analyzed, revealing promising activity and ease of preparation.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Jerome P. L. Ng, Yu Han, Li Jun Yang, Lyn-Marie Birkholtz, Dina Coertzen, Ho Ning Wong, Richard K. Haynes, Paolo Coghi, Vincent Kam Wai Wong
Summary: Artemisinin, a compound derived from the traditional Chinese medicinal plant Artemisia annua, is commonly used for malaria treatment. However, the emergence of drug resistance has prompted the search for new drug combinations. This study found that the triterpenoid quinone methide celastrol, isolated from the traditional Chinese medicinal plant Tripterygium wilfordii, displayed good antimalarial activity in combination with amino-artemisinins. Celastrol also showed synergistic effects against liver cancer cells. However, further modifications are needed to mitigate its toxicity.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Crystallography
Keyao Li, Monalisa Roy, Madiha Nisar, Lawrence W-Y Wong, Herman H-Y Sung, Richard K. Haynes, Ian D. Williams
Summary: This study demonstrates the formation of different types of cocrystals using different seeds, while also showing the role of halogen bonds in discriminating between different polymorphic types.
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
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
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)