+ paper

_bibliography/papers.bib

@@ -1,50 +1,49 @@
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-@ARTICLE{Rehborg2023-mj,
-  title    = "Mapping resistance-associated anthelmintic interactions in the
-              model nematode Caenorhabditis elegans",
-  author   = "Rehborg, Elena G and Wheeler, Nicolas J and Zamanian, Mostafa",
-  abstract = "Parasitic nematodes infect billions of people and are mainly
-              controlled by anthelmintic mass drug administration (MDA). While
-              there are growing efforts to better understand mechanisms of
-              anthelmintic resistance in human and animal populations, it is
-              unclear how resistance mechanisms that alter susceptibility to
-              one drug affect the interactions and efficacy of drugs used in
-              combination. Mutations that alter drug permeability across
-              primary nematode barriers have been identified as potential
-              resistance mechanisms using the model nematode Caenorhabditis
-              elegans . We leveraged high-throughput assays in this model
-              system to measure altered anthelmintic susceptibility in response
-              to genetic perturbations of potential cuticular, amphidial, and
-              alimentary routes of drug entry. Mutations in genes associated
-              with these tissue barriers differentially altered susceptibility
-              to the major anthelmintic classes (macrocyclic lactones,
-              benzimidazoles, and nicotinic acetylcholine receptor agonists) as
-              measured by animal development. We investigated two-way
-              anthelmintic interactions across C. elegans genetic backgrounds
-              that confer resistance or hypersensitivity to one or more drugs.
-              We observe that genetic perturbations that alter susceptibility
-              to a single drug can shift the drug interaction landscape and
-              lead to the appearance of novel synergistic and antagonistic
-              interactions. This work establishes a framework for investigating
-              combinatorial therapies in model nematodes that can potentially
-              be translated to amenable parasite species.",
-  journal  = "PLoS Negl. Trop. Dis.",
-  volume   =  17,
-  number   =  10,
-  pages    = "e0011674",
-  month    =  oct,
-  year     =  2023,
+@ARTICLE{Mian2024-gs,
+  title    = "Development of non-sedating antischistosomal benzodiazepines",
+  author   = "Mian, Md Yeunus and Sharmin, Dishary and Mondal, Prithu and
+              Belayet, Jawad Bin and Mahmun Hossain, M and McCusker, Paul and
+              Ryan, Kaetlyn T and Fedorov, Alexander Y and Green, Heather A and
+              Ericksen, Spencer S and Zamanian, Mostafa and Phani Babu
+              Tiruveedhula, V V and Cook, James M and Chan, John D",
+  abstract = "The neglected tropical disease schistosomiasis infects over 200
+              million people worldwide and is treated with just one broad
+              spectrum antiparasitic drug (praziquantel). Alternative drugs are
+              needed in the event of emerging praziquantel resistance or
+              treatment failure. One promising lead that has shown efficacy in
+              animal models and a human clinical trial is the benzodiazepine
+              meclonazepam, discovered by Roche in the 1970's. Meclonazepam was
+              not brought to market because of dose-limiting sedative side
+              effects. However, the human target of meclonazepam that causes
+              sedation (GABAARs) are not orthologous to the parasite targets
+              that cause worm death. Therefore, we were interested in whether
+              the structure of meclonazepam could be modified to produce
+              antiparasitic benzodiazepines that do not cause host sedation. We
+              synthesized 18 meclonazepam derivatives with modifications at
+              different positions on the benzodiazepine ring system and tested
+              them for in vitro antiparasitic activity. This identified five
+              compounds that progressed to in vivo screening in a murine model,
+              two of which cured parasite infections with comparable potency to
+              meclonazepam. When these two compounds were administered to mice
+              that were run on the rotarod test, both were less sedating than
+              meclonazepam. These findings demonstrate the proof of concept
+              that meclonazepam analogs can be designed with an improved
+              therapeutic index, and point to the C3 position of the
+              benzodiazepine ring system as a logical site for further
+              structure-activity exploration to further optimize this chemical
+              series. \#\#\# Competing Interest Statement The authors have
+              declared no competing interest.",
+  journal  = "bioRxiv",
+  pages    = "2024.01.26.577323",
+  month    =  jan,
+  year     =  2024,
   keywords = "Zamanian Papers",
   language = "en",
-  issn     = "1935-2727, 1935-2735",
-  pmid     = "37782672",
-  doi      = "10.1371/journal.pntd.0011674",
-  pmc      = "PMC10569609",
-  pdf      = {Rehborg et al. 2023 - Mapping resistance-associated anthelmintic interactions in the model nematode Caenorhabditis elegans.pdf},
-  preview  = {Rehborg et al. 2023 - Mapping resistance-associated anthelmintic interactions in the model nematode Caenorhabditis elegans.jpeg},
-  github = {AnthelminticInteractions-ms}
+  doi      = "10.1101/2024.01.26.577323",
+  pdf      = {Mian et al. 2024 - Development of non-sedating antischistosomal benzodiazepines.pdf},
+  preview  = {Mian et al. 2024 - Development of non-sedating antischistosomal benzodiazepines.jpeg}
 }
 
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