Ten new differently substituted 3-benzyl-5-aryl-3,5-dihydro-4H-benzo[6,7]chromeno[2,3-d]pyrimidin-4,6,11-triones 3 were synthesized by a simple and cost-efficient procedure in a one-pot, three-component reaction from readily available ethyl 2-amino-4-aryl-5,10-dioxo-5,10-dihydro-4H-benzo[g]chromene-3-carboxylates, benzylamine and triethyl orthoformate under solvent- and catalyst-free conditions. All the new compounds were screened for their antiproliferative activity against two colorectal-cancer-cell lines. The results showed that the compounds 3-benzyl-5-phenyl-3,5-dihydro-4H-benzo[6,7]chromeno[2,3-d]pyrimidine-4,6,11-trione (3a) and 3-benzyl-5-(3-hydroxyphenyl)-3,5-dihydro-4H-benzo[6,7]chromeno[2,3-d]pyrimidine-4,6,11-trione (3g) exhibited the most potent balanced inhibitory activity against human LoVo and HCT-116 cancer cells.
Background:
Drug repositioning is becoming an ideal strategy to select new anticancer drugs. In
particular, drugs treating the side effects of chemotherapy are the best candidates.
Objective:
In this present work, we undertook the evaluation of anti-tumour activity of two anti-diarrheal drugs
(nifuroxazide and rifaximin).
Methods:
Anti-proliferative effect against breast cancer cells (MDA-MB-231, MCF-7 and T47D) was assessed
by MTT analysis, the Brdu incorporation, mitochondrial permeability and caspase-3 activity.
Results:
Both the drugs displayed cytotoxic effects on MCF-7, T47D and MDA-MB-231 cells. The lowest IC50
values were obtained on MCF-7 cells after 24, 48 and 72 hours of treatment while T47D and MDA-MB-231
were more resistant. The IC50 values on T47D and MDA-MB-231 cells became significantly low after 72 hours
of treatment showing a late cytotoxicity effect especially of nifuroxazide but still less important than that of
MCF-7 cells. According to the IC50 values, the non-tumour cell line HEK293 seems to be less sensitive to cytotoxicity
especially against rifaximin. Both the drugs have shown an accumulation of rhodamine 123 as a function
of the rise of their concentrations while the Brdu incorporation decreased. Despite the absence of a significant
difference in the cell cycle between the treated and non-treated MCF-7 cells, the caspase-3 activity increased
with the drug concentrations rise suggesting an apoptotic effect.
Conclusion:
Nifuroxazide and rifaximin are used to overcome the diarrheal side effect of anticancer drugs.
However, they have shown to be anti-tumour drugs which make them potential dual effective drugs against
cancer and the side effects of chemotherapy.
A series of new [1,2,4]triazolo[4,3-a]pyrimidine derivatives was prepared using a one-pot three-component synthesis from 5-amino-1-phenyl-1H-1,2,4-triazoles, aromatic aldehydes and ethyl acetoacetate. The compound structures were confirmed by IR, 1H-NMR, 13C-NMR, HRMS and X-ray analyses. The biological activity of these compounds as antitumor agents was evaluated. Their antitumor activities against cancer cell lines (MDA-MB-231 and MCF-7) were tested by the MTT in vitro method. Among them, compounds 4c and 4j displayed the best antitumor activity with IC50 values of 17.83 μM and 19.73 μM against MDA-MB-231 and MCF-7 cell lines, respectively, compared to the Cisplatin reference.
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