2 research outputs found
Palladium(II)-Catalyzed Synthesis of 2<i>H</i>,3′<i>H</i>‑Spiro[benzofuran-3,2′-naphthoquinones]
2<i>H</i>,3′<i>H</i>-Spiro[benzofuran-3,2′-naphthoquinones],
constituting a new spiroheterocyclic skeleton, were synthesized starting
from 2-aryloxymethyl-1,4-naphthoquinones by means of a palladium(II)-catalyzed
reaction, which is a new spirocyclic transformation. Under optimal
conditions, i.e. 10 mol % of palladium(II) acetate, 15 mol % of 3,5-dichloropyridine,
and 5 mol % of trifluoroacetic acid in acetic acid at 110 °C,
various 2<i>H</i>,3′<i>H</i>-spiro[benzofuran-3,2′-naphthoquinones]
were synthesized in yields strongly dependent on the substitution
pattern of the aryloxy group. Unsubstituted or <i>ortho</i>-substituted 2-aryloxymethyl-1,4-quinones were found to rearrange
toward the corresponding 2-(4-hydroxyaryl)-1,4-quinones upon treatment
with trifluoroacetic acid
1,2,3,4,8,9,10,11-Octahydrobenzo[<i>j</i>]phenanthridine-7,12-diones as New Leads against Mycobacterium tuberculosis
Tuberculosis
(TB) continues to be a worldwide health problem with
over 1.4 million deaths each year. Despite efforts to develop more
effective vaccines, more reliable diagnostics, and chemotherapeutics,
tuberculosis remains a threat to global health, fueled by the HIV
pandemic and the rapid generation of drug resistance. The exploration
of novel drugs to serve as a companion drug for existing drugs is
of paramount importance. As part of our program to design new 2-aza-anthraquinones
with antimycobacterial activity, various tetrahydro- and octahydrobenzo[<i>j</i>]phenanthridinediones were synthesized. These compounds
showed high in vitro potency against Mycobacterium
tuberculosis, the etiological agent of TB and against
other clinically relevant mycobacterial species at submicromolar concentrations.
The susceptibility of a multidrug resistant strain toward these compounds
and their ability to target intracellular replicating Mycobacterium tuberculosis was demonstrated. Next
to the acute toxicity, the genotoxicity of these compounds was investigated.
Often overlooked in studies, genotoxicity could be dismissed for the
investigated compounds, making them a promising scaffold in TB drug
research