3-Aryl-2-quinolone derivates were extensively investigated for their inhibition of farnesyl transferase. Taking this as a cue, we studied the other possible mechanism of antitumor activity of 2-quinolone derivates. A series of new 2-quinolone derivatives have been synthesized and screened for their cytotoxicity by trypan blue assay on Ehrlich ascites carcinoma cells and MTT assay on MCF-7 cells. Compound 1a (nJST) was found to be more effective in both studies with the lowest CTC 50 value among all nine synthesized compounds. This compound was further screened on four different cell lines, viz. human breast adenocarcinoma (MCF-7, MDA-MB-231), colon cancer (HCT-15), murine melanoma (B16F10) cell lines for 24 and 48 h. The CTC 50 value of the compound was found to be <10 lM. Compound 1a induced DNA damage which was revealed by DNA fragmentation studies and further confirmed by nuclear staining. The compound also showed significant elevation in Bax and reduction Bcl-2 gene expression levels. Acute toxicity study in mice indicated that the compound is safe till 2000 mg ⁄ kg. Two different doses 50 and 100 mg ⁄ kg were selected and studied in Ehrlich ascites carcinoma model of cancer and have shown significant improvement in survival time and hematological parameters. Treatment for cancer is still being a challenge for medical world. Many researches are going on to get a safe and effective treatment for this disease. 2-Quinolones are one of the molecules in this category. Joseph et al. initiated the exploration of anticancer potential of this moiety by reporting a series of 2-quinolones with 3-aryl and N-alkyl substitutions of which 12 compounds were exhibiting cytotoxicity (CTC 50 ) of more than 10 lM on MCF-7 (human breast cancer) cell line. However, these compounds were found to be nontoxic in in vivo toxicity determination and effective in in vivo model of MXT mouse mammary adenocarcinoma (1).The leading molecule of this category, tipifarnib, is still in clinical trial stage. This molecule is also have 3-aryl and N-methylation substitutions and exhibits cytotoxicity in breast cancer cell lines MDA-MB-231 and BT-474 with a CTC 50 value <30 lM (2). Moreover, it is active orally and causes apoptosis in myeloid leukemia cell line (3).Apoptosis plays a central role in study of carcinogenesis and drug development for the cancer therapy. It is a regulated evolutionary conserved programme of cell suicide. Disturbance in this physiological programme prolongs the life of cell and leads to carcinogenesis. In cancer cells, the apoptosis diminishes and causes dominance of anti-apoptotic protein. Mitochondrial-mediated apoptosis is controlled by anti-apoptotic (Bcl-2) and proapoptotic (Bax and Bad) proteins of Bcl-2 family. Overexpression of Bcl-2 occurs in 40-80% of human breast cancers (4).These studies added rising interest in developing and evaluating anticancer activity of 2-quinolone derivatives through apoptotic pathway. Among quinolones, most of the anticancer compounds have a 3-aryl substitution. However, to our knowl...

The oxadiazole moiety is known for its anticancer activity through its antiangiogenic and mitostatic potential. Taking this as a cue, the present study was designed to investigate the anti-cancer potential of selected oxadiazole derivatives. Twelve 1,3,4-oxadiazole derivatives (AMK OX-1 to AMK OX-12) were synthesized and were tested for IC 50 values through brine shrimp lethality assay and MTT assay on HeLa and A549 cell lines. Four compounds, AMK OX-8, 9, 11 and 12 showed potential cytotoxicity activity with low IC 50 value. These compounds produced considerable cytotoxic effect on Hep-2 and A549 cancer cell lines. However, they were found to be comparatively safer to normal cell lines, viz., V-79 cell lines than to the tested cancer cell lines, such as HeLa, A 549, and Hep2 cell lines. The mechanism of cytotoxicity was evaluated through nuclear staining and DNA ladder assay. Although DNA ladder assay showed DNA fragmentation (apoptotic phenomenon) in Hep-2 cells treated with only AMK OX-12, the staining procedures using acridine orange, ethidium bromide and propidium iodide showed apoptotic bodies in cells treated with AMK OX-8, 9 and 12 also. In JCI staining on isolated mitochondria of Hep2 cells, AMK OX-8, 9-11 and 12 displayed increasing fluorescence intensity with time which confirmed involvement of mitochondrial pathway and intrinsic pathway of apoptosis. All four compounds were found to be safe in acute oral toxicity study in Swiss albino mice. These derivatives were effective in reducing tumor size and weight in the in vivo DLA-induced solid tumor model. They were found to be significantly effective in reducing tumor volume and tumor weight.

Objective:To investigate the total alkaloid fraction of the methanol extract of leaves of Hygrophila auriculata for its hepatoprotective activity against CCl4-induced toxicity in freshly isolated rat hepatocytes, HepG2 cells, and animal models.Materials and Methods:Mature leaves of H. auriculata were collected, authenticated, and subjected to methanolic extraction followed by isolation of total alkaloid fraction. Freshly isolated rat hepatocytes were exposed to CCl4 (1%) along with/without various concentrations of the total alkaloid fraction (80–40 µg/ml). Protection of human liver-derived HepG2 cells against CCl4-induced damage was determined by the MTT assay. Twenty-four healthy Wistar albino rats (150–200 g) of either sex were used for the in vivo investigations. Liver damage was induced by administration of 30% CCl4 suspended in olive oil (1 ml/kg body weight, i.p).Results:The antihepatotoxic effect of the total alkaloid fraction was observed in freshly isolated rat hepatocytes at very low concentrations (80–40 µg/ml). A dose-dependent increase in the percentage viability was observed when CCl4-exposed HepG2 cells were treated with different concentrations of the total alkaloid fraction. Its in vivo hepatoprotective effect at 80 mg/kg body weight was comparable with that of the standard Silymarin at 250 mg/kg body weight.Conclusion:The total alkaloid fraction was able to normalize the biochemical levels which were altered due to CCl4 intoxication.