Design, Synthesis, and Biological Evaluation of Newly Synthesized Cinnamide-Fluorinated Containing Compounds as Bioactive Anticancer Agents.

A new series of cinnamide-fluorinated derivatives has been synthesized and characterized by using different spectroscopic and elemental microanalyses methods. All of the prepared p-fluorocinnamide derivatives were evaluated for their cytotoxic activity against the HepG2 liver cancerous cell line. The imidazolone derivative 6, which bears N-(N-pyrimidin-2-ylbenzenesulphamoyl) moiety, displayed antiproliferative activity against HepG2 liver cancerous cells with an IC50 value of 4.23 µM as compared to staurosporin (STU) (IC50 = 5.59 µM). In addition, compound 6 experienced epidermal growth factor receptor (EGFR) inhibitory activity comparable to palatinib. The cell cycle analysis by flow cytometry indicated that compound 6 arrested the cellular cycle of HepG2 cells at the G1 phase. Additionally, as demonstrated by the fluorescence-activated cell sorting (FACS) technique, compound 6 increased both early and late apoptotic ratios compared to control untreated HepG2 cells. Moreover, imidazolone compound 6 induced apoptosis via the intrinsic apoptotic pathway by decreasing the level of mitochondrial membrane polarization (MMP) compared to untreated HepG2 cells. Therefore, the new N-(N-pyrimidin-2-ylbenzenesulphamoyl)imidazolone derivative 6 could be considered a potential platform for further optimizing an antitumor agent against hepatocellular carcinoma.

Sucrose esters of aryldihydronaphthalene-type lignans, and antitumor activity of extracts of Moltkiopsis ciliata (Forssk.) aerial parts.

One new compound (3f-[(7'R,8'R)-4,4'-dihydroxy-5-methoxy-2,7'-cycloligna-7-en-9-methoxycarbonyl, 9'-carbonyl-O-] -ß- D-fructofuranosyl- (2→1)-α- D-glucopyranoside) (Moltkiopsin A) (2) was isolated and identified from the extract of aerial parts of the wild Egyptian plant Moltkiopsis ciliata (Frossk.), family Boraginaceae, for the first time, along with two aryldihydronaphthalene lignans 3f→9':6f→9-[(7'R,8'R)-4,4'- dihydroxy-3,3',5-trimethoxy-2,7'-cycloligna-7-en-9,9'-dicarbonyl]-6g-acetyl-α-D-gluco pyranosyl-(1→2) -ß-D-fructofuranoside (Trigonotin A) (1) which was reported for the first time from this plant species and a known compound 3f→9':6f→9-[(7'R,8'R)-4,4'- dihydroxy-3,3',5-trimethoxy-2,7'-cycloligna-7-en-9,9'-dicarbonyl]-α-D-gluco pyranosyl - (1→2)- ß-D- fructofuranoside (Trigonotin C) (3). These compounds were separated and purified using different chromatographic techniques and their structures were elucidated by extensive 1D (1H and 13C NMR), and 2D NMR (COSY, HSQC, and HMBC), besides ESI-MS spectral methods. Extracts were screened as antioxidant, antitumor and antibacterial. The different extracts showed moderate to strong antioxidant capacities in DPPH assays. Ethyl acetate, methylene chloride and crude methanol extracts exhibited the most significant free radicals scavenging activity when compared to the standard antioxidant vitamin C. Hexane and butanol fractions showed the highest cytotoxicity against the cancer cell lines HepG2 and MCF-7.