3 research outputs found
Synthesis, Antitumor Activity, and Mechanism of Action of Benzo[<i>b</i>]chromeno[6,5‑<i>g</i>][1,8]naphthyridin-7-one Analogs of Acronycine
A series
of 6-methoxy-3,3,14-trimethyl-3,14-dihydro-<i>7H</i>-benzo[<i>b</i>]chromeno[6,5<i>-g</i>][1,8]naphthyridin-7-one
(<b>4</b>), 13-aza derivatives of benzo[<i>b</i>]acronycine,
the isomeric 5-methoxy-2,2,13-trimethyl-2,13-dihydro-<i>6H-</i>benzo[<i>b</i>]chromeno[7,6<i>-g</i>][1,8]naphthyridin-6-one
(<b>5</b>), and related <i>cis</i>-diols mono- and
diesters were designed and synthesized. Their <i>in vitro</i> and <i>in vivo</i> biological activities were evaluated.
As previously observed in the acronycine series, esters were the most
potent derivatives exhibiting submicromolar activities; among them
monoesters are particularly active. Racemic diacetate <b>21</b> showed a strong activity against KB-3-1 cell lines and was selected
for <i>in vivo</i> evaluation and proved to be active, inhibiting
tumor growth by more than 80%. After separation of the two enantiomers,
compounds <b>21a</b> and <b>21b</b> were also evaluated
against C38 colon adenocarcinoma; their activities were found to be
significantly different
Natural Inhibitors of the RhoA–p115 Complex from the Bark of <i>Meiogyne baillonii</i>
In an effort to find potent natural
inhibitors of RhoA and p115
signaling G-proteins, a systematic in vitro evaluation using enzymatic
and plasmonic resonance assays was undertaken on 11 317 plant
extracts. The screening procedure led to the selection of the New
Caledonian endemic species <i>Meiogyne baillonii</i> for
a chemical investigation. Using a bioguided isolation procedure, three
enediyne-γ-butyrolactones (<b>1</b>–<b>3</b>) and two enediyne-γ-butenolides (<b>4</b> and <b>5</b>), named sapranthins H–L, respectively, two enediyne
carboxylic acid (<b>6</b> and <b>7</b>), two depsidones,
stictic acid (<b>8</b>) and baillonic acid (<b>9</b>),
aristolactams AIa and AIIa (<b>10</b> and <b>11</b>),
and two aporphines, dehydroroemerine (<b>12</b>) and noraristolodione
(<b>13</b>), were isolated from the ethyl acetate extract of
the bark. The structures of the new compounds (<b>1</b>–<b>6</b>, <b>9</b>, and <b>11</b>) and their relative
configurations were established by NMR spectroscopic analysis and
by X-ray diffraction analysis for compound <b>9</b>. Only stictic
acid (<b>8</b>) exhibited a significant inhibiting activity
of the RhoA–p115 complex, with an EC<sub>50</sub> value of
0.19 ± 0.05 mM. This is the first time that a natural inhibitor
of the complex RhoA–p115’s activity was discovered from
an HTS performed over a collection of higher plant extracts. Thus,
stictic acid (<b>8</b>) could be used as the first reference
compound inhibiting the interaction between RhoA and p115
Natural Inhibitors of the RhoA–p115 Complex from the Bark of <i>Meiogyne baillonii</i>
In an effort to find potent natural
inhibitors of RhoA and p115
signaling G-proteins, a systematic in vitro evaluation using enzymatic
and plasmonic resonance assays was undertaken on 11 317 plant
extracts. The screening procedure led to the selection of the New
Caledonian endemic species <i>Meiogyne baillonii</i> for
a chemical investigation. Using a bioguided isolation procedure, three
enediyne-γ-butyrolactones (<b>1</b>–<b>3</b>) and two enediyne-γ-butenolides (<b>4</b> and <b>5</b>), named sapranthins H–L, respectively, two enediyne
carboxylic acid (<b>6</b> and <b>7</b>), two depsidones,
stictic acid (<b>8</b>) and baillonic acid (<b>9</b>),
aristolactams AIa and AIIa (<b>10</b> and <b>11</b>),
and two aporphines, dehydroroemerine (<b>12</b>) and noraristolodione
(<b>13</b>), were isolated from the ethyl acetate extract of
the bark. The structures of the new compounds (<b>1</b>–<b>6</b>, <b>9</b>, and <b>11</b>) and their relative
configurations were established by NMR spectroscopic analysis and
by X-ray diffraction analysis for compound <b>9</b>. Only stictic
acid (<b>8</b>) exhibited a significant inhibiting activity
of the RhoA–p115 complex, with an EC<sub>50</sub> value of
0.19 ± 0.05 mM. This is the first time that a natural inhibitor
of the complex RhoA–p115’s activity was discovered from
an HTS performed over a collection of higher plant extracts. Thus,
stictic acid (<b>8</b>) could be used as the first reference
compound inhibiting the interaction between RhoA and p115