Structure-Activity Relationships, Tolerability and Efficacy of Microtubule-Active 1,2,4-Triazolo[1,5-a]pyrimidines as Potential Candidates to Treat Human African Trypanosomiasis
ChemMedChem. 2023 Jul 10:e202300193. doi: 10.1002/cmdc.202300193. Online ahead of print.ABSTRACTTubulin and microtubules (MTs) are potential protein targets to treat parasitic infections and our previous studies have shown that the triazolopyrimidine (TPD) class of MT-active compounds hold promise as antitrypanosomal agents. MT-targeting TPDs include structurally related but functionally diverse congeners that interact with mammalian tubulin at either one or two distinct interfacial binding sites; namely, the seventh and vinca sites, which are found within or between α,β-tubulin heterodimers, respectively. Evaluation of ...
Source: ChemMedChem - July 10, 2023 Category: Chemistry Authors: 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 Source Type: research
Structure-Activity Relationships, Tolerability and Efficacy of Microtubule-Active 1,2,4-Triazolo[1,5-a]pyrimidines as Potential Candidates to Treat Human African Trypanosomiasis
ChemMedChem. 2023 Jul 10:e202300193. doi: 10.1002/cmdc.202300193. Online ahead of print.ABSTRACTTubulin and microtubules (MTs) are potential protein targets to treat parasitic infections and our previous studies have shown that the triazolopyrimidine (TPD) class of MT-active compounds hold promise as antitrypanosomal agents. MT-targeting TPDs include structurally related but functionally diverse congeners that interact with mammalian tubulin at either one or two distinct interfacial binding sites; namely, the seventh and vinca sites, which are found within or between α,β-tubulin heterodimers, respectively. Evaluation of ...
Source: ChemMedChem - July 10, 2023 Category: Chemistry Authors: 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 Source Type: research
[ASAP] Development of a 2,4-Diaminothiazole Series for the Treatment of Human African Trypanosomiasis Highlights the Importance of Static –Cidal Screening of Analogues
Journal of Medicinal ChemistryDOI: 10.1021/acs.jmedchem.3c00509 (Source: Journal of Medicinal Chemistry)
Source: Journal of Medicinal Chemistry - June 21, 2023 Category: Chemistry Authors: Laura A. T. Cleghorn, Richard J. Wall, Se ́bastien Albrecht, Stuart A. MacGowan, Suzanne Norval, Manu De Rycker, Andrew Woodland, Daniel Spinks, Stephen Thompson, Stephen Patterson, Victoriano Corpas Lopez, Gourav Dey, Iain T. Collie, Irene Hallyburton, Source Type: research
Exploring N-myristoyltransferase as a promising drug target against parasitic neglected tropical diseases
Eur J Med Chem. 2023 Jun 8;258:115550. doi: 10.1016/j.ejmech.2023.115550. Online ahead of print.ABSTRACTNeglected tropical diseases (NTDs) constitute a group of approximately 20 infectious diseases that mainly affect the impoverished population without basic sanitation in tropical countries. These diseases are responsible for many deaths worldwide, costing billions of dollars in public health investment to treat and control these infections. Among them are the diseases caused by protozoa of the Trypanosomatid family, which constitute Trypanosoma cruzi (Chagas disease), Trypanosoma brucei (sleeping sickness), and Leishmania...
Source: European Journal of Medicinal Chemistry - June 19, 2023 Category: Chemistry Authors: Igor Jos é Dos Santos Nascimento Misael de Azevedo Teot ônio Cavalcanti Ricardo Olimpio de Moura Source Type: research
Exploring N-myristoyltransferase as a promising drug target against parasitic neglected tropical diseases
Eur J Med Chem. 2023 Jun 8;258:115550. doi: 10.1016/j.ejmech.2023.115550. Online ahead of print.ABSTRACTNeglected tropical diseases (NTDs) constitute a group of approximately 20 infectious diseases that mainly affect the impoverished population without basic sanitation in tropical countries. These diseases are responsible for many deaths worldwide, costing billions of dollars in public health investment to treat and control these infections. Among them are the diseases caused by protozoa of the Trypanosomatid family, which constitute Trypanosoma cruzi (Chagas disease), Trypanosoma brucei (sleeping sickness), and Leishmania...
Source: European Journal of Medicinal Chemistry - June 19, 2023 Category: Chemistry Authors: Igor Jos é Dos Santos Nascimento Misael de Azevedo Teot ônio Cavalcanti Ricardo Olimpio de Moura Source Type: research
Exploring N-myristoyltransferase as a promising drug target against parasitic neglected tropical diseases
Eur J Med Chem. 2023 Jun 8;258:115550. doi: 10.1016/j.ejmech.2023.115550. Online ahead of print.ABSTRACTNeglected tropical diseases (NTDs) constitute a group of approximately 20 infectious diseases that mainly affect the impoverished population without basic sanitation in tropical countries. These diseases are responsible for many deaths worldwide, costing billions of dollars in public health investment to treat and control these infections. Among them are the diseases caused by protozoa of the Trypanosomatid family, which constitute Trypanosoma cruzi (Chagas disease), Trypanosoma brucei (sleeping sickness), and Leishmania...
Source: European Journal of Medicinal Chemistry - June 19, 2023 Category: Chemistry Authors: Igor Jos é Dos Santos Nascimento Misael de Azevedo Teot ônio Cavalcanti Ricardo Olimpio de Moura Source Type: research
Hemoglobin uptake and utilization by human protozoan parasites: a review
The protozoan disease is a major global health concern. Amoebiasis, leishmaniasis, Chagas disease, and African sleeping sickness affect several million people worldwide, leading to millions of deaths annually and immense social and economic problems. Iron is an essential nutrient for nearly all microbes, including invading pathogens. The majority of iron in mammalian hosts is stored intracellularly in proteins, such as ferritin and hemoglobin (Hb). Hb, present in blood erythrocytes, is a very important source of iron and amino acids for pathogenic microorganisms ranging from bacteria to eukaryotic pathogens, such as worms,...
Source: Frontiers in cellular and infection microbiology - June 9, 2023 Category: Microbiology Source Type: research
Evidence-based advice on timing and location of tsetse control measures in Shimba Hills National reserve, Kenya
by Stella Gachoki, Thomas A. Groen, Anton Vrieling, Andrew Skidmore, Daniel Masiga
Controlling tsetse flies is critical for effective management of African trypanosomiasis in Sub-Saharan Africa. To enhance timely and targeted deployment of tsetse control strategies a better understanding of their temporal dynamics is paramount. A few empirical studies have explained and predicted tsetse numbers across space and time, but the resulting models may not easily scale to other areas. We used tsetse catches from 160 traps monitored between 2017 and 2019 around Shimba Hills National Reserve in Kenya, a known tsetse and trypanosom...
Source: PLoS Neglected Tropical Diseases - June 5, 2023 Category: Tropical Medicine Authors: Stella Gachoki Source Type: research
SA1 Identification of Patients Diagnosed with Rare and Emerging Diseases Utilizing Real-World Claims Data - A Case Study of African and American Trypanosomiasis
This study aimed to explore patient profiles of African trypanosomiasis and American trypanosomiasis, both vector-borne parasitic diseases, using a US claims database and to compare this to previously published patient profiles. (Source: Value in Health)
Source: Value in Health - June 1, 2023 Category: International Medicine & Public Health Authors: K. Madaj, J. Brauneis, J. Menon, V. Seshadri, C. Vossen Tags: Study Approaches Source Type: research
Influence of amino acid size at the P3 position of N-Cbz-tripeptide Michael acceptors targeting falcipain-2 and rhodesain for the treatment of malaria and human african trypanosomiasis
Bioorg Chem. 2023 May 4;137:106587. doi: 10.1016/j.bioorg.2023.106587. Online ahead of print.ABSTRACTIn recent decades, several structure-activity relationship (SAR) studies provided potent inhibitors of the cysteine proteases falcipain-2 (FP-2) and rhodesain (RD) from Plasmodium falciparum and Trypanosoma brucei rhodesiense, respectively. Whilst the roles of the warhead and residues targeting the P1 and P2 pockets of the proteases were extensively investigated, the roles of the amino acids occupying the S3 pocket were not widely assessed. Herein we report the synthesis and biological evaluation of a set of novel Michael a...
Source: Bioorganic Chemistry - May 10, 2023 Category: Chemistry Authors: Santo Previti Roberta Ettari Carla Di Chio Jenny Legac Marta Bogacz Collin Zimmer Tanja Schirmeister Philip J Rosenthal Maria Zappal à Source Type: research
Influence of amino acid size at the P3 position of N-Cbz-tripeptide Michael acceptors targeting falcipain-2 and rhodesain for the treatment of malaria and human african trypanosomiasis
Bioorg Chem. 2023 May 4;137:106587. doi: 10.1016/j.bioorg.2023.106587. Online ahead of print.ABSTRACTIn recent decades, several structure-activity relationship (SAR) studies provided potent inhibitors of the cysteine proteases falcipain-2 (FP-2) and rhodesain (RD) from Plasmodium falciparum and Trypanosoma brucei rhodesiense, respectively. Whilst the roles of the warhead and residues targeting the P1 and P2 pockets of the proteases were extensively investigated, the roles of the amino acids occupying the S3 pocket were not widely assessed. Herein we report the synthesis and biological evaluation of a set of novel Michael a...
Source: Bioorganic Chemistry - May 10, 2023 Category: Chemistry Authors: Santo Previti Roberta Ettari Carla Di Chio Jenny Legac Marta Bogacz Collin Zimmer Tanja Schirmeister Philip J Rosenthal Maria Zappal à Source Type: research
Type-I like metalloproteinase in the venom of the West African saw-scaled carpet viper (Echis ocellatus) has anti-trypanosomal activity against African trypanosomes
Toxicon. 2023 Apr 29:107138. doi: 10.1016/j.toxicon.2023.107138. Online ahead of print.ABSTRACTAfrican trypanosomiasis is an infectious disease caused by hemoparasites of the genus Trypanosoma and remains a major health problem in Africa - killing around 4000 people and animals worth an estimated $5 billion, annually. The absence of a vaccine and satisfactory drug against African trypanosomiasis (AT) necessitates the continued search for new chemotherapy options. Owing to the rich biochemical diversity in snake venom, it has recently become a source of therapeutic peptides that are being explored for the development of nov...
Source: Toxicon - May 1, 2023 Category: Toxicology Authors: Ameh Ilu Mathias A Chia Thais R Cataldi Carlos A Labate Godwin U Ebiloma Peter O Yusuf Mohammed N Shuaibu Emmanuel O Balogun Source Type: research
Type-I like metalloproteinase in the venom of the West African saw-scaled carpet viper (Echis ocellatus) has anti-trypanosomal activity against African trypanosomes
Toxicon. 2023 Apr 29:107138. doi: 10.1016/j.toxicon.2023.107138. Online ahead of print.ABSTRACTAfrican trypanosomiasis is an infectious disease caused by hemoparasites of the genus Trypanosoma and remains a major health problem in Africa - killing around 4000 people and animals worth an estimated $5 billion, annually. The absence of a vaccine and satisfactory drug against African trypanosomiasis (AT) necessitates the continued search for new chemotherapy options. Owing to the rich biochemical diversity in snake venom, it has recently become a source of therapeutic peptides that are being explored for the development of nov...
Source: Toxicon - May 1, 2023 Category: Toxicology Authors: Ameh Ilu Mathias A Chia Thais R Cataldi Carlos A Labate Godwin U Ebiloma Peter O Yusuf Mohammed N Shuaibu Emmanuel O Balogun Source Type: research
Type-I like metalloproteinase in the venom of the West African saw-scaled carpet viper (Echis ocellatus) has anti-trypanosomal activity against African trypanosomes
Toxicon. 2023 Apr 29:107138. doi: 10.1016/j.toxicon.2023.107138. Online ahead of print.ABSTRACTAfrican trypanosomiasis is an infectious disease caused by hemoparasites of the genus Trypanosoma and remains a major health problem in Africa - killing around 4000 people and animals worth an estimated $5 billion, annually. The absence of a vaccine and satisfactory drug against African trypanosomiasis (AT) necessitates the continued search for new chemotherapy options. Owing to the rich biochemical diversity in snake venom, it has recently become a source of therapeutic peptides that are being explored for the development of nov...
Source: Toxicon - May 1, 2023 Category: Toxicology Authors: Ameh Ilu Mathias A Chia Thais R Cataldi Carlos A Labate Godwin U Ebiloma Peter O Yusuf Mohammed N Shuaibu Emmanuel O Balogun Source Type: research
Type I-like metalloproteinase in the venom of the West African saw-scaled carpet viper (Echis ocellatus) has anti-trypanosomal activity against African trypanosomes
Toxicon. 2023 Apr 29;229:107138. doi: 10.1016/j.toxicon.2023.107138. Online ahead of print.ABSTRACTAfrican trypanosomiasis is an infectious disease caused by hemoparasites of the genus Trypanosoma and remains a major health problem in Africa - killing around 4000 people and animals worth an estimated $5 billion, annually. The absence of a vaccine and satisfactory drug against African trypanosomiasis (AT) necessitates the continued search for new chemotherapy options. Owing to the rich biochemical diversity in snake venom, it has recently become a source of therapeutic peptides that are being explored for the development of...
Source: Toxicon - May 1, 2023 Category: Toxicology Authors: Ameh Ilu Mathias A Chia Thais R Cataldi Carlos A Labate Godwin U Ebiloma Peter O Yusuf Mohammed N Shuaibu Emmanuel O Balogun Source Type: research
