Article
Chemistry, Medicinal
Baljinder Singh, Amrita Sharma, Naresh Gunaganti, Mitch Rivers, Pradip K. Gadekar, Brady Greene, Michael Chichioco, Carlos E. Sanz-Rodriguez, Courtney Fu, Catherine LeBlanc, Erin Burchfield, Nyle Sharif, Benjamin Hoffman, Gaurav Kumar, Andrei Purmal, Kojo Mensa-Wilmot, Michael P. Pollastri
Summary: New analogs of the carbazole CBL0137 were synthesized and evaluated, resulting in the discovery of eight compounds with higher or equivalent selectivity indices. Among them, 5v demonstrated potential for drug development against human African trypanosomiasis (HAT), while 5w showed lack of efficacy. Lessons from these studies will guide further optimization of carbazoles for HAT and other indications.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Baljinder Singh, Amrita Sharma, Naresh Gunaganti, Mitch Rivers, Pradip K. Gadekar, Brady Greene, Michael Chichioco, Carlos E. Sanz-Rodriguez, Courtney Fu, Catherine LeBlanc, Erin Burchfield, Nyle Sharif, Benjamin Hoffman, Gaurav Kumar, Andrei Purmal, Kojo Mensa-Wilmot, Michael P. Pollastri
Summary: To develop a candidate drug against human African trypanosomiasis (HAT), researchers synthesized new analogs and evaluated their properties. Eight new compounds with higher or equivalent selectivity indices were identified. Two compounds, 5v and 5w, were tested in a mouse model of HAT, and 5v showed a lead-like profile for drug development while 5w lacked efficacy. These findings will guide further optimization of carbazoles for HAT and other indications.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Editorial Material
Multidisciplinary Sciences
Dalmeet Singh Chawla
Summary: A shortage of participants leads to longer duration of pediatric trials and reduced financial incentives for pharmaceutical companies.
Article
Biochemical Research Methods
Maryam Aliee, Matt J. Keeling, Kat S. Rock
Summary: This study investigates the role of asymptomatic infections in the elimination of Gambiense African sleeping sickness transmission, showing that these infections may significantly impact transmission and hinder progress towards achieving elimination goals. Location-specific modeling and research are needed to determine if asymptomatic infections pose a threat.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Review
Veterinary Sciences
Keneth Iceland Kasozi, Ewan Thomas MacLeod, Ibrahim Ntulume, Susan Christina Welburn
Summary: African trypanosomiasis, both in animals and humans, is associated with different pathogens and drug resistance. Research is being conducted on new combination therapies.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Review
Veterinary Sciences
Keneth Iceland Kasozi, Ewan Thomas MacLeod, Susan Christina Welburn
Summary: The resistance of African animal trypanocide is a continuous threat to the elimination of African trypanosomiasis. This study investigated the threat by using major chemotherapeutic agents and found multi-drug cross-resistance, emphasizing the need to revise policies for disease control.
FRONTIERS IN VETERINARY SCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Mudasir Nabi Peerzada, Aysha Gaur, Amir Azam
Summary: This review discusses drug development strategies for human African and American trypanosomiasis, highlighting the most promising compounds identified through various approaches and emphasizing the potential of molecular hybridization in preventing the development of resistance.
CURRENT MEDICINAL CHEMISTRY
(2021)
Review
Medicine, General & Internal
Vittoria Lutje, Katrin Probyn, Jorge Seixas, Hanna Bergman, Gemma Villanueva
Summary: The study evaluated the effectiveness and safety of current drugs for treating second-stage Trypanosoma brucei gambiense trypanosomiasis. Oral treatment with fexinidazole is easier to administer but may lead to higher mortality and relapse compared to conventional treatment.
COCHRANE DATABASE OF SYSTEMATIC REVIEWS
(2021)
Article
Public, Environmental & Occupational Health
Olaf Valverde Mordt, Antoine Tarral, Nathalie Strub-Wourgaft
Summary: This article describes the strategy used to simplify the introduction of a new oral treatment for human African trypanosomiasis. The authors discuss various aspects of the drug's development, including determining dosage range, testing food effects, optimizing absorption, establishing partnerships, and preparing for regulatory approval and distribution. The article highlights the importance of early preparation and collaboration in successfully bringing the new treatment to affected regions.
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
(2022)
Article
Public, Environmental & Occupational Health
Victor Kande Betu Kumesu, Wilfried Mutombo Kalonji, Clelia Bardonneau, Olaf Valverde Mordt, Digas Ngolo Tete, Severine Blesson, Francois Simon, Sophie Delhomme, Sonja Bernhard, Pathou Nganzobo Ngima, Helene Mahenzi Mbembo, Jean-Pierre Fina Lubaki, Steven Lumeya Vuvu, Willy Kuziena Mindele, Medard Ilunga Wa Kyhi, Guylain Mandula Mokenge, Lewis Kaninda Badibabi, Augustin Kasongo Bonama, Papy Kavunga Lukula, Crispin Lumbala, Bruno Scherrer, Nathalie Strub-Wourgaft, Antoine Tarral
Summary: The multicentre clinical trial of oral fexinidazole in pediatric patients with gambiense human African trypanosomiasis demonstrated that the drug is a safe and effective first-line treatment option across all disease stages.
LANCET GLOBAL HEALTH
(2022)
Article
Chemistry, Medicinal
Ludovica Monti, Lawrence J. Liu, Carmine Varricchio, Bobby Lucero, Thibault Alle, Wenqian Yang, Ido Bem-Shalom, Michael Gilson, Kurt R. Brunden, Andrea Brancale, Conor R. Caffrey, Carlo Ballatore
Summary: Triazolopyrimidine (TPD) compounds have potential as antitrypanosomal agents by targeting tubulin and microtubules. Evaluation of 123 TPD congeners led to the identification of two compounds with promising in vivo pharmacokinetics, tolerability, and efficacy against Trypanosoma brucei. Further optimization of dosing and schedule may lead to alternative treatments for human African trypanosomiasis.
Article
Pharmacology & Pharmacy
Antoine Tarral, Lionel Hovsepian, Thierry Duvauchelle, Yves Donazzolo, Mathilde Latreille, Mathieu Felices, Virginie Gualano, Sophie Delhomme, Olaf Valverde Mordt, Severine Blesson, Pascal Voiriot, Nathalie Strub-Wourgaft
Summary: This study determined the best dose regimen for Acoziborole, a novel boron-containing drug for the treatment of HAT. The drug was well tolerated at all tested doses and had a long duration of action. The findings suggest that Acoziborole could potentially be used as a single-dose oral cure for both stages of HAT.
CLINICAL PHARMACOKINETICS
(2023)
Review
Chemistry, Medicinal
Mohd Imran, Shah Alam Khan, Mohammed Kanan Alshammari, Ashwaq Muiedh Alqahtani, Turkiah Abdullah Alanazi, Mehnaz Kamal, Talha Jawaid, Mohammed M. Ghoneim, Sultan Alshehri, Faiyaz Shakeel
Summary: This study reviews the discovery, development, inventions, and patent literature of fexinidazole (FEX), which has been approved as the first all-oral therapy for Human African trypanosomiasis (HAT). The review highlights the potential for further inventions and innovations based on FEX for the treatment of other diseases.
Article
Biochemistry & Molecular Biology
Hisham A. Elrufaie, Linda M. Mohamed, Aya Y. Hamd, Noor A. Bala, Fatima A. Elbadawi, Hiba Ghaboosh, Abdulrahim A. Alzain
Summary: This study used computational methods to identify natural products that inhibit the parasitic enzyme Rhodesain. Three potential compounds were found, which showed excellent binding affinity and stability towards Rhodesain. These compounds may be a hopeful treatment for Human African Trypanosomiasis (HAT) in the future if further clinical trials were conducted.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Immunology
Mariame Camara, Alseny M'mah Soumah, Hamidou Ilboudo, Christelle Travaille, Caroline Clucas, Anneli Cooper, Nono-Raymond Kuispond Swar, Oumou Camara, Ibrahim Sadissou, Estefania Calvo Alvarez, Aline Crouzols, Jean-Mathieu Bart, Vincent Jamonneau, Mamadou Camara, Annette MacLeod, Bruno Bucheton, Brice Rotureau
Summary: In the study of gambiense human African trypanosomiasis, it was found that live parasites may remain undetected in the blood of some seropositive individuals but are present in their skin. The skin may serve as a potential reservoir for African trypanosomes.
CLINICAL INFECTIOUS DISEASES
(2021)