Explanipedia

Synthesis of pyrazolyl acrylamide-chalcone conjugates with sub-micromolar antitrypanosomal activities Open

Devesh S. Agarwal, Karol R. Francisco, Richard M. Beteck, Yashpreet Kaur, Aiqiang Cheng , et al. · 2025

A series of compounds was synthesized in 3 steps and studied for their activity against Trypanosoma brucei, the causative agent of human African trypanosomiasis. These compounds were also evaluated for their cytotoxicity against the HEK293…

Structure-Activity Relationship and Target Investigation of Thiophen-2-yl-Pyrimidines against Schistosoma species Open

Karol R. Francisco, Bobby Lucero, Darius J. Yohannan, Carmine Varricchio, Angela M. Lam , et al. · 2025

Chemotherapeutic options for schistosomiasis, a prevalent infectious disease of poverty, are limited to just one drug, praziquantel (PZQ), and alternatives are needed. Our previous studies identified thiophen-2-yl pyrimidines (TPPs), which…

Photoaffinity labeling of protein targets in a complex metazoan: proof-of-concept using a probe for Schistosoma mansoni tubulin Open

Bobby Lucero, Thibault Alle, M Bufano, Yuemang Yao, Kurt R. Brunden , et al. · 2025

Treatment of schistosomiasis, a prevalent neglected tropical disease, relies precariously on a single drug. The discovery and development of alternative anti-schistosomal small molecules most often relies on phenotypic (whole-organism) scr…

Synthesis and in vitro anti-trypanosomal evaluation of quinolone hydrazide analogues Open

Phelelisiwe S. Dube, Sarah Makgoba, Karol R. Francisco, Lesetja J. Legoabe, Conor R. Caffrey , et al. · 2025

African trypanosomiasis is a major health threat to humans and animals in 36 countries within sub-Saharan Africa. We previously identified quinolone hydrazides exhibiting sub-micromolar anti-trypanosomal activity. However, the most potent …

Synthesis of Pyrazolyl Acrylamide-Chalcone Conjugates with Sub-Micromolar Antitrypanosomal Activities Open

Devesh S. Agarwal, Karol R. Francisco, Richard M. Beteck, Yashpreet Kaur, Aiqiang Cheng , et al. · 2025

A series of compounds was synthesized in 4-5 steps and studied for their activity against Trypanosoma brucei, the causative agent of human African trypanosomiasis. These compounds were also evaluated for their cytotoxicity against the HEK2…

Carmaphycin B-Based Proteasome Inhibitors to Treat Human African Trypanosomiasis: Structure–Activity Relationship and In Vivo Efficacy Open

Lawrence J. Liu, Karol R. Francisco, Yujie Uli Sun, Mateus Sá Magalhães Serafim, Dilini K. Amarasinghe , et al. · 2024

The proteasome is essential for eukaryotic cell proteostasis, and inhibitors of the 20S proteasome are progressing preclinically and clinically as antiparasitics. We screenedTrypanosoma brucei, the causative agent of human and anima…

Structure activity relationships of antischistosomal N-phenylbenzamides by incorporation of electron-withdrawing functionalities Open

Ameera Mohammed Dawoodjee, John Sichinga, Harrison Banda, Steve Mbaya, Evelyn Funjika , et al. · 2024

For the adult Schistosoma mansoni flatworm pathogen, we report further structure activity relationships (SAR) of 19 N-phenylbenzamide analogs. Our previous SAR studies, designed by selecting representative substituents from t…

Clickable Probes for Pathogen Proteasomes: Synthesis and Applications Open

Lawrence J. Liu, Bobby Lucero, Cindy Manriquez-Rodriguez, Karol R. Francisco, Thaiz R. Teixeira , et al. · 2024

The 20S proteasome is a multimeric protease complex that is essential for proteostasis in the cell. Small molecule proteasome inhibitors are approved drugs for various cancers and are advancing clinically as antiparasitics. Although tools …

Tractable Quinolone Hydrazides Exhibiting Sub‐Micromolar and Broad Spectrum Antitrypanosomal Activities Open

Kgothatso A. Chirwa, Karol R. Francisco, Phelelisiwe S. Dube, Ha-Young Park, Lesetja J. Legoabe , et al. · 2024

Nagana and Human African Trypanosomiasis (HAT), caused by (sub)species of Trypanosoma , are diseases that impede human and animal health, and economic growth in Africa. The few drugs available have drawbacks including suboptimal efficacy, …

Design, Synthesis, and Evaluation of An Anti‐trypanosomal [1,2,4]Triazolo[1,5‐a]pyrimidine Probe for Photoaffinity Labeling Studies Open

Bobby Lucero, Karol R. Francisco, Carmine Varricchio, Lawrence J. Liu, Yuemang Yao , et al. · 2024

Studies have shown that depending on the substitution pattern, microtubule (MT)‐targeting 1,2,4‐triazolo[1,5‐ a ]pyrimidines (TPDs) can produce different cellular responses in mammalian cells that may be due to these compounds interacting …

Structure Activity Relationships of Antischistosomal N-Phenylbenzamides by Incorporation of Electron-Withdrawing Functionalities Open

Peter Mubanga Cheuka, Ameera Mohammed Dawoodjee, John Sichinga, Harrison Banda, Steve Mbaya , et al. · 2024

Targeted Reversible Covalent Modification of a Noncatalytic Lysine of the Krev Interaction Trapped 1 Protein Enables Site-Directed Screening for Protein–Protein Interaction Inhibitors Open

Karol R. Francisco, Jessica Bruystens, Carmine Varricchio, Sara McCurdy, Jian Wu , et al. · 2023

The covalent reversible modification of proteins is a validated strategy for the development of probes and candidate therapeutics. However, the covalent reversible targeting of noncatalytic lysines is particularly challenging. Herein, we c…

CCDC 2246686: Experimental Crystal Structure Determination Open

Thibault Alle, Sipak Joyasawal, Killian Oukoloff, Keith Long, Zachary Owyang , et al. · 2023

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available …

Structure-property relationships of fluorinated carboxylic acid bioisosteres Open

Thibault Alle, Sipak Joyasawal, Killian Oukoloff, Keith Long, Zachary Owyang , et al. · 2023

Fluorinated alcohols and phenols are potentially useful as bioisosteres of the carboxylic acid functional group. To enable a direct comparison of the properties of fluorinated carboxylic acid surrogates with those of other commonly used, n…

Protein–protein interactions: developing small-molecule inhibitors/stabilizers through covalent strategies Open

Bobby Lucero, Karol R. Francisco, Lawrence J. Liu, Conor R. Caffrey, Carlo Ballatore · 2023

The development of small-molecule inhibitors or stabilizers of selected protein-protein interactions (PPIs) of interest holds considerable promise for the development of research tools as well as candidate therapeutics. In this context, th…

Hydrogen Bonding Parameters by Rapid Colorimetric Assessment: Evaluation of Structural Components Found in Biological Ligands and Organocatalysts Open

Hanna F. Roenfanz, Thomas J. Paniak, Cameron B. Berlin, Van Tran, Karol R. Francisco , et al. · 2023

Hydrogen bonding is a key molecular interaction in biological processes, drug delivery, and catalysis. This report describes a high throughput UV‐Vis spectroscopic method to measure hydrogen bonding capacity using a pyrazinone sensor. This…

Activity of N-phenylbenzamide analogs against the neglected disease pathogen, Schistosoma mansoni Open

Masebe Kanyanta, Chilufya Lengwe, Dickson Mambwe, Karol R. Francisco, Lawrence J. Liu , et al. · 2023

Structure-activity relationship of dibenzylideneacetone analogs against the neglected disease pathogen, Trypanosoma brucei Open

Karol R. Francisco, Ludovica Monti, Wenqian Yang, Ha-Young Park, Lawrence J. Liu , et al. · 2023

Trypanosoma brucei is a protozoan parasite that causes Human African Trypanosomiasis (HAT), a neglected tropical disease (NTD) that is endemic in 36 countries in sub-Saharan Africa. Only a handful drugs are available for treatment, and the…

Microtubule-Stabilizing 1,2,4-Triazolo[1,5-a]pyrimidines as Candidate Therapeutics for Neurodegenerative Disease: Matched Molecular Pair Analyses and Computational Studies Reveal New Structure–Activity Insights Open

Thibault Alle, Carmine Varricchio, Yuemang Yao, Bobby Lucero, Goodwell Nzou , et al. · 2022

Microtubule (MT)-stabilizing 1,2,4-triazolo[1,5-a]pyrimidines (TPDs) hold promise as candidate therapeutics for Alzheimer's disease (AD) and other neurodegenerative conditions. However, depending on the choice of substituents around…

A Broad Spectrum Antiparasitic Activity of Organotin (IV) Derivatives and Its Untargeted Proteomic Profiling Using Leishmania donovani Open

Obaid Hayat, Nazif Ullah, Muhammad Sirajuddin, Miriam A. Giardini, Jennifer V. Nguyen , et al. · 2022

Metals have been used in medicine since ancient times for the treatment of different ailments with various elements such as iron, gold and arsenic. Metal complexes have also been reported to show antibiotic and antiparasitic activity. In t…

Evaluation of log P, pKa, and log D predictions from the SAMPL7 blind challenge Open

Teresa Danielle Bergazin, Nicolas Tielker, Yingying Zhang, Junjun Mao, M. R. Gunner , et al. · 2021

The Statistical Assessment of Modeling of Proteins and Ligands (SAMPL) challenges focuses the computational modeling community on areas in need of improvement for rational drug design. The SAMPL7 physical property challenge dealt with pred…

Evaluation of Log P, pKa and Log D Predictions from the SAMPL7 Blind Challenge Open

Teresa Danielle Bergazin, Nicolas Tielker, Yingying Zhang, Junjun Mao, M. R. Gunner , et al. · 2021

The Statistical Assessment of Modeling of Proteins and Ligands (SAMPL) challenges focuses the computational modeling community on areas in need of improvement for rational drug design. The SAMPL7 physical property challenge dealt with pred…

Evaluation of Log P, pKa and Log D Predictions from the SAMPL7 Blind Challenge Open

Teresa Danielle Bergazin, Nicolas Tielker, Yingying Zhang, Junjun Mao, M. R. Gunner , et al. · 2021

The Statistical Assessment of Modeling of Proteins and Ligands (SAMPL) challenges focuses the computational modeling community on areas in need of improvement for rational drug design. The SAMPL7 physical property challenge dealt with pred…

CCDC 1995771: Experimental Crystal Structure Determination Open