3 research outputs found
Synthesis and Evaluation of N-(3-Trifluoroacetylindol- 7-yl) Acetamides for Potential In Vitro Antiplasmodial Properties
A series of novel N-((2,5-diaryl-3-trifluoroacetyl)-1H-indol-7-yl)acetamides has been prepared
via a successive and one-pot reaction sequence involving initial trifluoroacetic acid-mediated Beckmann
rearrangement of the oximes derived from the 1-(2,5-diaryl-1H-indol-7-yl)ethanones, followed
by trifluoroacetylation of the incipient N-(2,5-diaryl-1H-indol-7-yl)-acetamides with trifluoroacetic
anhydride. The prepared compounds were evaluated for potential in vitro antiplasmodial properties.
Preliminary results from antiplasmodial activity against the chloroquine-sensitive 3D7 strain of
Plasmodium falciparum revealed that a combination of 2-(4-flurophenyl)- and 5-(4-fluorophenyl) or
2-(4-flurophenyl)- and 4-fluorostyryl groups in compounds 3(a,f) and 4(a,g), for example, is required for
biological activity for both series of compounds. Their possible mode of action against the plasmodial
parasite is explained theoretically through molecular docking of the most active compounds against
the parasite lactate dehydrogenase (pLDH). These compounds were docked at the entrance of NAD+
in pLDH presumably hindering entry of lactate to cause the observed inhibition effect of pLDH.
The four compounds were found to exhibit low toxicity against monkey kidney Vero cells at the highest
concentrations tested
Synthesis, biological evaluation and molecular docking of novel indole-aminoquinazoline hybrids for anticancer properties
A series of indole-aminoquinazolines was prepared via amination of the
2-aryl-4-chloroquinazolines with the 7-amino-2-aryl-5-bromoindoles. It was then evaluated for
cytotoxicity in vitro against human lung cancer (A549), epithelial colorectal adenocarcinoma (Caco-2),
hepatocellular carcinoma (C3A), breast adenocarcinoma (MCF-7), and cervical cancer (HeLa)
cells. A combination on the quinazoline and indole moieties of a 2-phenyl and 2-(4-fluorophenyl)
rings in compound 4b; 2-(4-fluorophenyl) and 3-chlorophenyl rings in compound 4f; or the two
2-(4-fluorophenyl) rings in compound 4g, resulted in significant and moderate activity against the
Caco-2 and C3A cell lines. The indole-aminoquinazoline hybrids compounds 4f and 4g induced
apoptosis in Caco-2 and C3A cells, and were also found to exhibit moderate (IC50 = 52.5 nM) and
significant (IC50 = 40.7 nM) inhibitory activity towards epidermal growth factor receptor (EGFR)
against gefitinib (IC50 = 38.9 nM). Molecular docking suggests that 4a–h could bind to the ATP region
of EGFR like erlotinib.The University of South Africa, University of Pretoria and the National
Research Foundation.http://www.mdpi.com/journal/ijmsam2018ChemistryParaclinical Science