Design, Synthesis and Cytotoxic Evaluation of Novel Chalcone Derivatives Bearing Triazolo[4,3-a]-quinoxaline Moieties as Potent Anticancer Agents with Dual EGFR Kinase and Tubulin Polymerization Inhibitory Effects

A series of hybrid of triazoloquinoxaline-chalcone derivatives 7a–k were designed, synthesized, fully characterized, and evaluated for their cytotoxic activity against three target cell lines: human breast adenocarcinoma (MCF-7), human colon carcinoma (HCT-116), and human hepatocellular carcinoma (HEPG-2). The preliminary results showed that some of these chalcones like 7b–c, and 7e–g exhibited significant antiproliferative effects against most of the cell lines, with selective or non-selective behavior, indicated by IC50 values in the 1.65 to 34.28 µM range. In order to investigate the mechanistic aspects of these active compounds, EGFR TK and tubulin inhibitory activities were measured as further biological assays. The EGFR TK assay results revealed that the derivatives 7a–c, 7e, and 7g could inhibit the EGFR TK in the submicromolar range (0.093 to 0.661 µM). Moreover, an antitubulin polymerization effect was noted for the active derivatives compared to the reference drug colchicine, with compounds 7e and 7g displaying 14.7 and 8.4 micromolar activity, respectively. Furthermore, a molecular docking study was carried out to explain the observed effects and the binding modes of these chalcones with the EGFR TK and tubulin targets

Three trocar laparoscopic Roux-en-y gastric bypass: A novel technique en route to the single-incision laparoscopic approach

AbstractBackgroundLaparoscopic Roux-en-Y gastric bypass is the gold standard bariatric procedure. Typically, the procedure necessitates five to seven small skin incisions for trocar placement. The senior author (AA Saber) has developed a three-trocar approach for laparoscopic Roux-en-Y gastric bypass.MethodsSixteen patients underwent triple-incision laparoscopic Roux-en-Y gastric bypass between May 2009 and August 2009. The same surgeon performed all surgical interventions. The umbilicus was the main point of entry for all patients and the same operative technique and perioperative protocol were used in all patients.ResultsA total of sixteen triple-incision laparoscopic Roux-en-Y gastric bypasses were performed. The procedures were successfully performed in all patients. Mean operating time was 145.4 min. None of the patients required conversion to an open procedure. There were no mortalities or post-operative technical complications noted during the immediate post-operative period.ConclusionThree trocar laparoscopic Roux-en-Y gastric bypass is safe, technically feasible and reproducible. This technique may be considered a “precursor” to single-incision laparoscopic Roux-en-Y gastric bypass

Cytotoxic Activity of Zinc Oxide Nanoparticles Mediated by Euphorbia Retusa

Background: Cancer is a dangerous threat that creates extremely high rates of death and morbidity in various regions of the world. Finding suitable therapeutics to improve cancer therapy while avoiding side effects is critical. The most appropriate innovative therapeutics, which combine natural ingredients and nanomaterials, can improve the biological activity of cancer chemotherapeutics. Methods: Phenolic profiling using high-resolution mass spectrometry and the synthesis of zinc oxide nanoparticles was achieved through the reaction of zinc acetate with Euphorbia retusa extract. The characterization of ZnONPs was performed by UV, IR, Zeta potential, XRD, SEM, and TEM. The cytotoxic activity of the ZnONPs was evaluated using a SRB assay against lung, liver, and breast cancer cell lines. Moreover, the mechanism of cytotoxic activity was evaluated in the form of caspase-8 promoters and anti-inflammatory mechanisms using the Western blot method. Results: The high-resolution LC/MS/MS of the E. retusa led to the identification of 22 compounds in the plant for the first time. The Er-ZnONPs had hexagonal shapes, were approximately 100 nm in size, and consisted of aggregated particles of about 10 nm. The E. retusa ZnONPs exhibited cytotoxic activity against HA-549 (IC50 = 22.3 µg/mL), HepG2 (IC50 = 25.6), Huh-7 (IC50 = 25.7), MCF-7 (IC50 = 37.7), and MDA-MB-231 (IC50 = 37). Conclusions: E. retusa are rich in phenolics that are capable of synthesizing ZnONPs, which possess cytotoxic activity, via caspase-8 promotion and anti-inflammatory mechanisms

Protective Effects of Naringenin from <i>Citrus sinensis</i> (var. Valencia) Peels against CCl₄-Induced Hepatic and Renal Injuries in Rats Assessed by Metabolomics, Histological and Biochemical Analyses

Citrus fruits are grown worldwide for their special nutritive and several health benefits. Among citrus bioactives, naringenin, a major flavanone, exhibits a potential hepatoprotective effect that is not fully elucidated. Herein, serum biochemical parameters and histopathological assays were used to estimate the hepatoprotective activity of naringenin, isolated from Citrus sinensis (var. Valencia) peels, in CCl4-induced injury in a rat model. Further, GC–MS-based untargeted metabolomics was used to characterize the potential metabolite biomarkers associated with its activity. Present results revealed that naringenin could ameliorate the increases in liver enzymes (ALT and AST) induced by CCl4 and attenuate the pathological changes in liver tissue. Naringenin decreased urea, creatinine and uric acid levels and improved the kidney tissue architecture, suggesting its role in treating renal disorders. In addition, naringenin increased the expression of the antiapoptoic cell marker, Bcl-2. Significant changes in serum metabolic profiling were noticed in the naringenin-treated group compared to the CCl4 group, exemplified by increases in palmitic acid, stearic acid, myristic acid and lauric acids and decrease levels of alanine, tryptophan, lactic acid, glucosamine and glucose in CCl4 model rats. The results suggested that naringenin’s potential hepato- and renoprotective effects could be related to its ability to regulate fatty acids (FAs), amino acids and energy metabolism, which may become effective targets for liver and kidney toxicity management. In conclusion, the current study presents new insights into the hepato- and renoprotective mechanisms of naringenin against CCl4-induced toxicity