2-Pyridylquinolone antimalarials with improved antimalarial activity and physicochemical properties

Sitthivut Charoensutthivarakul; W. David Hong; Suet C. Leung; Peter D. Gibbons; Paul T.P. Bedingfield; Gemma L. Nixon; Alexandre S. Lawrenson; Neil G. Berry; Steve Ward; Giancarlo Biagini; Paul M. O'Neill

doi:10.1039/c5md00062a

2-Pyridylquinolone antimalarials with improved antimalarial activity and physicochemical properties

Sitthivut Charoensutthivarakul, W. David Hong, Suet C. Leung, Peter D. Gibbons, Paul T.P. Bedingfield, Gemma L. Nixon, Alexandre S. Lawrenson, Neil G. Berry, Steve Ward, Giancarlo Biagini, Paul M. O'Neill

Tropical Disease Biology

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

13 Citations (Scopus)

Abstract

A series of 2-pyridylquinolones has been prepared in 5–7 steps and through lead optimisation, antimalarial activity as low as 12 nM against Plasmodium falciparum (Pf) has been achieved. Compared with previous analogues in this series, selected molecules have improved solubility, a reduced potential for off-target toxicity and improved metabolic stability profiles. Docking studies performed with a homology model of the Pfbc1 complex target demonstrate a key role for the Tyr16 residues in the recognition of highly active quinolone based inhibitors

Original language	English
Pages (from-to)	1252-1259
Number of pages	8
Journal	RSC Medicinal Chemistry
Volume	6
Issue number	7
Early online date	19 May 2015
DOIs	https://doi.org/10.1039/c5md00062a
Publication status	Published - 1 Jul 2015

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MedChemComm 2-Pyridylquinolone AntimalarialsAccepted author manuscript, 685 KBLicence: CC BY

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title = "2-Pyridylquinolone antimalarials with improved antimalarial activity and physicochemical properties",

abstract = "A series of 2-pyridylquinolones has been prepared in 5–7 steps and through lead optimisation, antimalarial activity as low as 12 nM against Plasmodium falciparum (Pf) has been achieved. Compared with previous analogues in this series, selected molecules have improved solubility, a reduced potential for off-target toxicity and improved metabolic stability profiles. Docking studies performed with a homology model of the Pfbc1 complex target demonstrate a key role for the Tyr16 residues in the recognition of highly active quinolone based inhibitors",

author = "Sitthivut Charoensutthivarakul and Hong, \{W. David\} and Leung, \{Suet C.\} and Gibbons, \{Peter D.\} and Bedingfield, \{Paul T.P.\} and Nixon, \{Gemma L.\} and Lawrenson, \{Alexandre S.\} and Berry, \{Neil G.\} and Steve Ward and Giancarlo Biagini and O'Neill, \{Paul M.\}",

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doi = "10.1039/c5md00062a",

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AU - Charoensutthivarakul, Sitthivut

AU - Hong, W. David

AU - Leung, Suet C.

AU - Gibbons, Peter D.

AU - Bedingfield, Paul T.P.

AU - Nixon, Gemma L.

AU - Lawrenson, Alexandre S.

AU - Berry, Neil G.

AU - Ward, Steve

AU - Biagini, Giancarlo

AU - O'Neill, Paul M.

PY - 2015/7/1

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AB - A series of 2-pyridylquinolones has been prepared in 5–7 steps and through lead optimisation, antimalarial activity as low as 12 nM against Plasmodium falciparum (Pf) has been achieved. Compared with previous analogues in this series, selected molecules have improved solubility, a reduced potential for off-target toxicity and improved metabolic stability profiles. Docking studies performed with a homology model of the Pfbc1 complex target demonstrate a key role for the Tyr16 residues in the recognition of highly active quinolone based inhibitors

U2 - 10.1039/c5md00062a

DO - 10.1039/c5md00062a

M3 - Article

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EP - 1259

JO - RSC Medicinal Chemistry

JF - RSC Medicinal Chemistry

IS - 7

ER -

2-Pyridylquinolone antimalarials with improved antimalarial activity and physicochemical properties

Abstract

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