A series of ( Z )-2-(nitroheteroarylmethylene)-3(2 H )-benzofuranones possessing nitroheteroaryls groups of nitroimidazole, nitrofuran and nitrothiophene moieties was screened for antiplasmodium activity against drug-sensitive (3D7) as well as a chloroquine (CQ) and multi-drug resistant (K1) strains of P. falciparum 5-Nitroimidazole and 4-nitroimidazole analogs were highly selective and active against resistant parasites, while 5-nitrofuran and 5-nitrothiophene derivatives were more potent against the 3D7 strain than the K1 strain. Among the synthetic analogues, ( Z )-6-chloro-2-(1-methyl-5-nitroimidazol-2-ylmethylene)-3(2 H )-benzofuranone ( 5h ) exhibited the highest activity (IC 50 : 0.654 nM) against K1 strain and ( Z )-7-methoxy-2-(5-nitrothiophen-2-ylmethylene)-3(2 H )-benzofuranone ( 10g ) showed the highest activity (IC 50 : 0.28 μM) against the 3D7 strain in comparison with CQ (IC 50 s of 3.13 and 206.3 nM against 3D7 and K1 strains, respectively). The more active compounds with IC 50 s lower than 5 μg/mL (∼20 μM) were further studied for their cytotoxicity responses using KB cells. From these studies, 5-nitroimidazole, 4-nitroimidazole and 5-nitrofuran analogues were shown to be cytotoxic against KB cells, while 5-nitrothiophene analogues were shown to have the least cytotoxic effects. To gain some insight into their potential contributing mechanism of action, three derivatives 10e , 10g and 10h (from nitrothiophene subgroup possessing 6-methoxy, 7-methoxy and 6,7-dimethoxy substituents on their benzofuranone moieties, respectively) showing the least toxicity and highest selectivity indices were assessed for their β-hematin formation inhibition activity. 10g demonstrated the highest inhibition activity (IC 50 : 10.78 μM) in comparison with CQ (IC 50 : 2.63 μM) as the reference drug. Finally, these three analogues ( 10e , 10g and 10h ) were further evaluated for their in vivo activity against P. berghei /albino mice model (Peter’s test). Tested analogues were shown to be active, reducing the percentage of erythrocytes that contained parasites by 53.4, 48.8 and 32.4%, respectively.

Evaluating the effect of herbal extracts has been always interesting for cancer researchers considering that these natural materials could be suitable sources for finding new anti-cancer agents. In the present study, Acroptilon repens methanol extract had been evaluated for its cytotoxic effects in two human breast cancer cell lines, MCF-7 and MDA-MB-468, using MTT assay. The apoptosis potential had also been evaluated using annexin-V/propidium iodide assay, Hoechst 33258 staining and evaluating the cell cycle with flow cytometery. The MTT results showed cytotoxicity with IC50 values of 69.2 and 32.6 μg/mL for MCF-7 and MDA-MB-468 cells, respectively. The results of the apoptosis assays confirmed the apoptosis potential of the plant extract in the breast cancer cell lines suggesting A. repens for further cancer studies.

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Cytotoxic activity of gaillardin, a sesquiterpene lactone isolated from Inula oculus-christi L. (Asteraceae), was assessed in the human breast adenocarcinoma cell line MCF-7, human hepatocellular carcinoma cell line HepG-2, human non-small cell lung carcinoma cell line A-549, and human colon adenocarcinoma cell line HT-29, resulting in IC 50 values of 6.37, 6.20, 4.76, and 1.81 μg/mL, respectively, in the microculture tetrazolium-formazan MTT assay. In vitro apoptosis-inducing properties of gaillardin were also evaluated in MCF-7 cells with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nickend labeling (TUNEL) assay. The results suggest gaillardin as a candidate for further studies in cancer therapy