TY - JOUR
T1 - 2,3-Diphenyl-2,3-dihydro-4H-1,3-thiaza-4-one heterocycles inhibit growth and block completion of cytokinesis in kinetoplastid parasites
AU - Malfara, Madeline F.
AU - Silverberg, Lee J.
AU - DiMaio, John
AU - Lagalante, Anthony F.
AU - Olsen, Mark A.
AU - Madison, Ekaterina
AU - Povelones, Megan L.
N1 - Funding Information:
This work was supported by the National Science Foundation under grant number MCB-1651517 to MLP and by a Major Research Instrumentation Grant to Villanova University ( CHE-2018399 ). LJS was supported by internal funding from Penn State Schuylkill .
Publisher Copyright:
© 2021 The Authors
PY - 2021/9
Y1 - 2021/9
N2 - Kinetoplastid parasites are model eukaryotes with a complex cell cycle that is highly regulated both spatially and temporally. In addition, diseases caused by these parasites continue to have a significant impact on human and animal health worldwide. While there have been advancements in chemotherapy for these diseases, there is a continual need for an arsenal of compounds that have robust anti-parasite activity with minimal impact on the human host. While investigating a series of 2,3-diphenyl-2,3-dihydro-4H-1,3-thiaza-4-one heterocycles with potential activity against these parasites, we found a pyridothiazinone that inhibits growth of the monoxenous parasite Crithidia fasciculata and two life cycle stages of Trypanosoma brucei. This inhibition is more pronounced in T. brucei and is associated with an unusual pre-abscission cell cycle arrest. Exploring the mode of action for these and related compounds in kinetoplastids may provide tools with which to explore cell cycle regulation in these important organisms.
AB - Kinetoplastid parasites are model eukaryotes with a complex cell cycle that is highly regulated both spatially and temporally. In addition, diseases caused by these parasites continue to have a significant impact on human and animal health worldwide. While there have been advancements in chemotherapy for these diseases, there is a continual need for an arsenal of compounds that have robust anti-parasite activity with minimal impact on the human host. While investigating a series of 2,3-diphenyl-2,3-dihydro-4H-1,3-thiaza-4-one heterocycles with potential activity against these parasites, we found a pyridothiazinone that inhibits growth of the monoxenous parasite Crithidia fasciculata and two life cycle stages of Trypanosoma brucei. This inhibition is more pronounced in T. brucei and is associated with an unusual pre-abscission cell cycle arrest. Exploring the mode of action for these and related compounds in kinetoplastids may provide tools with which to explore cell cycle regulation in these important organisms.
UR - http://www.scopus.com/inward/record.url?scp=85111214541&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85111214541&partnerID=8YFLogxK
U2 - 10.1016/j.molbiopara.2021.111396
DO - 10.1016/j.molbiopara.2021.111396
M3 - Article
C2 - 34302898
AN - SCOPUS:85111214541
SN - 0166-6851
VL - 245
JO - Molecular and biochemical parasitology
JF - Molecular and biochemical parasitology
M1 - 111396
ER -
