Molecular Docking and In Vivo Biological Studies of Sodium Salt of 3-(4-Methyl-2-oxo-2-H-quinoline-7-yloxy)-3-phenylacrylic Acid As Anticancer Agent.

Quinoline derivatives possess several therapeutic properties. Aim: studying the anticancer effect of 3-(4-methyl-2-oxo-2-H-quinoline-7-yloxy)-3-phenylacrylic acid's sodium solution on the Ehrlich ascites carcinoma (EAC). Median lethal dose (LD50) and dose response curve was determined for sodium salt solution of 3-(4-methyl-2-oxo-2-H-quinoline-7-yloxy)-3-phenylacrylic acid, then diving a group of one hundred Swiss albino mice, which are all females, into five groups: group 1: (negative control) where intraperitoneally injected with saline into mice for 10 successive days; group 2 (positive control), also namely (EAC-bearing group): where the EAC cells were intraperitoneally injected into mice (2.5 × 106 cells/mouse) only one time on the first day; group 3 which is defined as the (therapeutic group) where the Na+ salt of the synthetic compound was injected into the peritoneum of the mice (2.5 mg/kg) the very first day after the injection of the EAC, then the compound was injected every two days for a period of 10 days; group 4 which is the (preventive group) where the sodium salt of the synthetic compound (2.5 mg/kg) was injected in the peritoneum of the mice the day before the injection of the EAC, then the compound was successively injected every day for a period of ten days; and group 5 which is the (drug group) in which mice were repeatedly injected) in their peritoneum with the sodium salt of the synthetic compound (2.5 mg/kg on a daily basis over a period of ten days. On the eleventh day of the trial, EAC cells were harvested from each mouse in a heparinized saline, in addition to blood samples, liver and kidney tissues which are also collected. Molecular docking showed that compound's sodium salt was docked into (PDB: 2R7G) and (PDB: 2R3I), which are the retinoblastoma protein receptor and the cyclin D-1 receptor respectively. Compared to those in the positive control group, mice in both the therapeutic and preventive groups, has shown a significant decrease in MDA, cyclin D-1 levels in the tissues of both liver and kidney tissues, in addition to the serum ALT, AST, CK-MB, and LDH activities, and the serum urea and creatinine concentration. However, mice in the formerly mentioned groups, both therapeutic and preventive groups, have shown an increase in the serum albumin, total protein, retinoblastoma protein in both liver and kidney tissues as well as the total antioxidant capacity, when compared to mice in the positive control group. It is worth mentioning that histopathological findings have confirmed that. Sodium salt of 3-(4-methyl-2-oxo-2H-quinoline-7-yloxy)-3-phenylacrylic acid showed potential in vivo anticancer and antioxidant effects against Ehrlich ascites carcinoma cells; (EAC cells).

Onion Extract Encapsulated on Nano Chitosan: a Promising Anticancer Agent.

BACKGROUND: Onion (Allium cepa) is very rich in nutritional and pharmaceutical components, such as saponins, tannins, alkaloids, steroids, and phenols. Many recent researches approved its anticancer activity against various cancer cell lines. In this paper, we attempt to improve its anticancer activity with encapsulation on nano chitosan. On the best of our knowledge, this is considered the first study that tries to increase the anticancer activity of the onion extract on nano chitosan. METHODS: An aqueous extract of the onion was prepared and the extract efficiency as anticancer agent was enhanced by encapsulating the extract on nano chitosan. The antioxidant capacity and the functional ingredients such as alkaloid, tannin, saponin, steroid, phenolic, and flavonoid in either the free or encapsulated one were estimated. Also, the anticancer activity of the two extracts was tested against different cell lines. RESULTS: Encapsulation of the extract on chitosan nano particles decreased IC50 in different cell lines and induced apoptosis through decreasing BCL-2 level and increasing caspase-3 and caspase-9 activity. CONCLUSION: Onion extract encapsulated on nano chitosan can be used as protective agents from cancer, antitumor, or act synergistically with the cancer chemotherapy. This greatly participates in improving the use of natural products in cancer therapy instead of chemotherapy.

In Vitro Antitumor Evaluation of Acrylic Acid Derivatives Bearing Quinolinone Moiety as Novel Anticancer Agents.

BACKGROUND: Due to the emergence of resistance to available anticancer agents, the demand for new cytotoxic agents has grown. OBJECTIVE: This study aims at synthesis and cytotoxic evaluation of new acrylic acid derivatives bearing quinolinone and halogenated quinolinone derivatives against three cancer cell lines. METHODS: New acrylic acid derivatives bearing quinolinone and halogenated quinolinone moieties were synthesized and screened for their cytotoxic activity against breast MCF-7, liver HepG2, and colon HCT-116 cancer cell lines. RESULTS: Molecules 3 and 8 showed the most potent cytotoxic activity against HCT-116. DNA flow cytometry assay showed cell cycle arrest at the G1 phase and cellular apoptosis. Moreover, molecules 3 and 8 showed cyclin-dependent kinase 2 (CDK2) inhibitory activity compared to the untreated control sample. CONCLUSION: Acrylic acid derivatives bearing quinolinone and halogenated quinolinone moieties represent an important core and could be used as a lead for further development of drug compounds in order to achieve promising therapeutic results.