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Synthesis and Investigation of Phthalazinones as Antitubercular Agents
Author(s) -
Santoso Kristiana T.,
Cheung ChenYi,
Hards Kiel,
Cook Gregory M.,
Stocker Bridget L.,
Timmer Mattie S. M.
Publication year - 2019
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201801805
Subject(s) - minimum inhibitory concentration , mycobacterium tuberculosis , nitro , chemistry , enzyme , mode of action , lead compound , inhibitory postsynaptic potential , stereochemistry , tuberculosis , biochemistry , biology , in vitro , medicine , organic chemistry , alkyl , pathology , neuroscience
A series of 2‐ and 7‐substituted phthalazinones was synthesised and their potential as anti‐tubercular drugs assessed via Mycobacterium tuberculosis (mc 2 6230) growth inhibition assays. All phthalazinones tested showed growth inhibitory activity (MIC <100 μ m ), and those compounds containing lipophilic and electron‐withdrawing groups generally exhibited better anti‐tubercular activity. Several lead compounds were identified, including 7‐((2‐amino‐6‐(4‐fluorophenyl)pyrimidin‐4‐yl)amino)‐2‐heptylphthalazin‐1(2 H )‐one (MIC=1.6 μ m ), 4‐tertbutylphthalazin‐2(1 H )‐one (MIC=3 μ m ), and 7‐nitro‐phthalazin‐1(2 H )‐one (MIC=3 μ m ). Mode of action studies indicated that selected pyrimidinyl‐phthalazinones may interfere with NADH oxidation, however, the mode of action of the lead compound is independent of this enzyme. MIC=minimum inhibitory concentration.
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