The structure - activity relationship of the antimalarial ozonide arterolane (OZ277)

Yuxiang Dong; Sergio Wittlin; Kamaraj Sriraghavan; Jacques Chollet; Susan Ann Charman; William Neil Charman; Christian Scheurer; Heinrich Urwyler; Josefina Santo Tomas; Christopher Snyder; Darren John Creek; Julia Morizzi; Maria Koltun; Hugues Matile; Xiaofang Wang; Maniyan Padmanilayam; Yuanqing Tang; Arnulf Dorn; Reto Brun; Jonathan Vennerstrom

doi:10.1021/jm901473S

The structure - activity relationship of the antimalarial ozonide arterolane (OZ277)

Yuxiang Dong, Sergio Wittlin, Kamaraj Sriraghavan, Jacques Chollet, Susan Ann Charman, William Neil Charman, Christian Scheurer, Heinrich Urwyler, Josefina Santo Tomas, Christopher Snyder, Darren John Creek, Julia Morizzi, Maria Koltun, Hugues Matile, Xiaofang Wang, Maniyan Padmanilayam, Yuanqing Tang, Arnulf Dorn, Reto Brun, Jonathan Vennerstrom

Research output: Contribution to journal › Article › Research › peer-review

80 Citations (Scopus)

Abstract

The structure and stereochemistry of the cyclohexane substituents of analogues of arterolane (OZ277) had little effect on potency against Plasmodium falciparum in vitro. Weak base functional groups were not required for high antimalarial potency, but they were essential for high antimalarial efficacy in P. berghei-infected mice. Five new ozonides with antimalarial efficacy and ADME profiles superior or equal to that of arterolane were identified.

Original language	English
Pages (from-to)	481 - 491
Number of pages	11
Journal	Journal of Medicinal Chemistry
Volume	53
DOIs	https://doi.org/10.1021/jm901473S
Publication status	Published - 2010

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10.1021/jm901473S

Cite this

Dong, Y., Wittlin, S., Sriraghavan, K., Chollet, J., Charman, S. A., Charman, W. N., Scheurer, C., Urwyler, H., Santo Tomas, J., Snyder, C., Creek, D. J., Morizzi, J., Koltun, M., Matile, H., Wang, X., Padmanilayam, M., Tang, Y., Dorn, A., Brun, R., & Vennerstrom, J. (2010). The structure - activity relationship of the antimalarial ozonide arterolane (OZ277). Journal of Medicinal Chemistry, 53, 481 - 491. https://doi.org/10.1021/jm901473S

Dong, Yuxiang ; Wittlin, Sergio ; Sriraghavan, Kamaraj ; Chollet, Jacques ; Charman, Susan Ann ; Charman, William Neil ; Scheurer, Christian ; Urwyler, Heinrich ; Santo Tomas, Josefina ; Snyder, Christopher ; Creek, Darren John ; Morizzi, Julia ; Koltun, Maria ; Matile, Hugues ; Wang, Xiaofang ; Padmanilayam, Maniyan ; Tang, Yuanqing ; Dorn, Arnulf ; Brun, Reto ; Vennerstrom, Jonathan. / The structure - activity relationship of the antimalarial ozonide arterolane (OZ277). In: Journal of Medicinal Chemistry. 2010 ; Vol. 53. pp. 481 - 491.

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title = "The structure - activity relationship of the antimalarial ozonide arterolane (OZ277)",

abstract = "The structure and stereochemistry of the cyclohexane substituents of analogues of arterolane (OZ277) had little effect on potency against Plasmodium falciparum in vitro. Weak base functional groups were not required for high antimalarial potency, but they were essential for high antimalarial efficacy in P. berghei-infected mice. Five new ozonides with antimalarial efficacy and ADME profiles superior or equal to that of arterolane were identified.",

author = "Yuxiang Dong and Sergio Wittlin and Kamaraj Sriraghavan and Jacques Chollet and Charman, {Susan Ann} and Charman, {William Neil} and Christian Scheurer and Heinrich Urwyler and {Santo Tomas}, Josefina and Christopher Snyder and Creek, {Darren John} and Julia Morizzi and Maria Koltun and Hugues Matile and Xiaofang Wang and Maniyan Padmanilayam and Yuanqing Tang and Arnulf Dorn and Reto Brun and Jonathan Vennerstrom",

year = "2010",

doi = "10.1021/jm901473S",

language = "English",

volume = "53",

pages = "481 -- 491",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

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Dong, Y, Wittlin, S, Sriraghavan, K, Chollet, J, Charman, SA , Charman, WN, Scheurer, C, Urwyler, H, Santo Tomas, J, Snyder, C, Creek, DJ, Morizzi, J, Koltun, M, Matile, H, Wang, X, Padmanilayam, M, Tang, Y, Dorn, A, Brun, R & Vennerstrom, J 2010, 'The structure - activity relationship of the antimalarial ozonide arterolane (OZ277)', Journal of Medicinal Chemistry, vol. 53, pp. 481 - 491. https://doi.org/10.1021/jm901473S

The structure - activity relationship of the antimalarial ozonide arterolane (OZ277). / Dong, Yuxiang; Wittlin, Sergio; Sriraghavan, Kamaraj; Chollet, Jacques; Charman, Susan Ann ; Charman, William Neil; Scheurer, Christian; Urwyler, Heinrich; Santo Tomas, Josefina; Snyder, Christopher; Creek, Darren John; Morizzi, Julia; Koltun, Maria; Matile, Hugues; Wang, Xiaofang; Padmanilayam, Maniyan; Tang, Yuanqing; Dorn, Arnulf; Brun, Reto; Vennerstrom, Jonathan.

In: Journal of Medicinal Chemistry, Vol. 53, 2010, p. 481 - 491.

Research output: Contribution to journal › Article › Research › peer-review

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AU - Sriraghavan, Kamaraj

AU - Chollet, Jacques

AU - Charman, Susan Ann

AU - Charman, William Neil

AU - Scheurer, Christian

AU - Urwyler, Heinrich

AU - Santo Tomas, Josefina

AU - Snyder, Christopher

AU - Creek, Darren John

AU - Morizzi, Julia

AU - Koltun, Maria

AU - Matile, Hugues

AU - Wang, Xiaofang

AU - Padmanilayam, Maniyan

AU - Tang, Yuanqing

AU - Dorn, Arnulf

AU - Brun, Reto

AU - Vennerstrom, Jonathan

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AB - The structure and stereochemistry of the cyclohexane substituents of analogues of arterolane (OZ277) had little effect on potency against Plasmodium falciparum in vitro. Weak base functional groups were not required for high antimalarial potency, but they were essential for high antimalarial efficacy in P. berghei-infected mice. Five new ozonides with antimalarial efficacy and ADME profiles superior or equal to that of arterolane were identified.

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