Hemisyntheses and In-silico Study of New Analogues of Carlina Oxide from Carthamus Caeruleus Roots.

AIM AND OBJECTIVE: Nowadays, developing effective antibiotics for bacterial control has become difficult due to increased resistance to the available medicines in the market. Essential oils possess interesting biological properties as some of their components have very powerful antiviral and antibacterial properties. Carthamus caeruleus is a plant that has antibacterial and antioxidant activity due to the presence of an acetylenic compound, Carlina oxide. The aim of this work was to provide, for the first time, the chemical modifications to the structure of Carlina oxide and the insilico study of these analogues. MATERIALS AND METHODS: The essential oil of Carthamus caeruleus was extracted by steam distillation in a Clevenger-type apparatus. Carlina oxide component was separated by column chromatography. Five new analogues were synthetized and identified by spectroscopic analyses (RMN, IR and SM). Molecular docking simulation study was performed using Molecular Operating Environment software (MOE) on three enzymes of bacterial origin (Streptococcus pyogenesis and Enterococcus faecalis). RESULTS: Five new compounds derived from Carlina oxide were synthesized (IM8-IM12), and their structures were characterized by infrared (IR), 1H and 13C nuclear magnetic resonance (NMR). The new synthesized compounds were evaluated as mSpeB, DHFR from Enterococcus faecalis and DNA gyrase inhibitors by a docking analysis using MOE. These results show interesting ligand interactions with the three enzymes, and the best result was attributed to the complexes formed with IM9, which had the lowest score. CONCLUSION: In fact, these new compounds could lead to powerful approaches for the research and development of new antibiotics.

Pharmaco-Analytical Study and Phytochemical Profile of Hydroethanolic Extract of Algerian Prickly Pear (Opuntia ficus-indica.L).

BACKGROUND: "Opuntia ficus-indica" (prickly pear) is the cactus member of the Cactaceae family as an important nutrient and food source. OBJECTIVE: The purpose of this study was to characterize the phytochemical composition of hydroalcoholic extract of prickly pear seeds that cause therapeutic effects. METHODS: Phytochemical screening based on simple tests and determination of secondary metabolites were performed by High-Performance Liquid with Diode-Array Detection (HPLC-DAD) analysis. For the pharmacological studies, the anti-inflammatory activity in rats was evaluated by carrageenaninduced inflammation, the description of the sedative activity was carried to the following behavioural tests, and the analgesic effect of the extract was assessed by the resistance induced by acetic acid, and the tail immersion test in mice. RESULTS: The test drug at 500 mg/kg dose showed a significant increase in mean latency in the TAIL FLICK test, and a decrease in the average number of twisting movements in the KOSTER test, thus, a significant anti-inflammatory activity in the pattern of paw edema induced by carrageenan, and an important sedative effect on the central nervous system. CONCLUSION: These data suggest that the seeds of the cactus "Opuntia ficus-indica" could be a potential source of natural compound and reveal that the hydroethanolic extract of this species is a promising source, as well as a therapeutic agent for the research of new natural active ingredients.

Alpha cyano-4-hydroxy-3-methoxycinnamic acid inhibits proliferation and induces apoptosis in human breast cancer cells.

This study investigated the underlying mechanism of 4-hydroxy-3-methoxycinnamic acid (ACCA), on the growth of breast cancer cells and normal immortal epithelial cells, and compared their cytotoxic effects responses. Treatment of breast cancer cells (MCF-7, T47D, and MDA-231) with ACCA resulted in dose- and time-dependent decrease of cell proliferation, viability in colony formation assay, and programmed cell death (apoptosis) with minimal effects on non-tumoral cells. The ability of ACCA to suppress growth in cancer cells not expressing or containing defects in p53 gene indicates a lack of involvement of this critical tumor suppressor element in mediating ACCA-induced growth inhibition. Induction of apoptosis correlated with an increase in Bax protein, an established inducer of programmed cell death, and the ratio of Bax to Bcl-2, an established inhibitor of apoptosis. We also documented the ability of ACCA to inhibit the migration and invasion of MDA-231 cells with ACCA in vitro. Additionally, tumor growth of MDA-231 breast cancer cells in vivo was dramatically affected with ACCA. On the basis of its selective anticancer inhibitory activity on tumor cells, ACCA may represent a promising therapeutic drug that should be further evaluated as a chemotherapeutic agent for human breast cancer.