Design, Synthesis of Amide Derivatives of Scutellarin And Their Anti-Leukemia And Neuroprotective Activities

A unique series of amide-scutellarin derivatives were designed and synthesized in order to develop the function of scutellarin further. The antiproliferative activity of all target compounds against two human leukaemia cell lines were evaluated. Among them, compounds 6g and 7c displayed the most antitumor activities against HL-60 and THP-1. Moreover, all compounds were also assayed for their neuroprotective activity against hydrogen peroxide (H2O2)-induced PC-12 cell injury, and the majority of the compounds had moderate to good neuroprotective properties. These findings confirmed that these target compounds could be used as anti-leukaemia and neuroprotective candicates in the future.

Scorpion Venom Antimicrobial Peptides Induce Caspase-1 Dependant Pyroptotic Cell Death

Within the last decade, several peptides have been identified according to their ability to inhibit the growth of microbial pathogens. These antimicrobial peptides (AMPs) are a part of the innate immune system of all living organisms. Many studies on their effects on prokaryotic microorganisms have been reported; some of these peptides have cytotoxic properties although the molecular mechanisms underlying their activity on eukaryotic cells remain poorly understood. Smp24 and Smp43 are novel cationic AMPs which were identified from the venom of the Egyptian scorpion Scorpio maurus palmatus. Smp24 and Smp43 showed potent activity against both Gram-positive and Gram-negative bacteria as well as fungi. Here we describe cytotoxicity of these peptides towards two acute leukaemia cell lines (myeloid (KG1-a) and lymphoid (CCRF-CEM) leukaemia cell lines) and three non-tumour cell lines CD34+ (hematopoietic stem progenitor from cord blood), HRECs (human renal epithelial cells) and HaCaT (human skin keratinocytes). Smp24 and Smp43 (4–256 µg/ml) decreased the viability of all cell lines, although HaCaT cells were markedly less sensitive. With the exception HaCaT cells, the caspase-1 gene was uniquely up-regulated in all cell lines studied. However, all cell lines showed an increase in downstream interleukin-1β (IL-1β) expression. Transmission electron microscope studies revealed the formation of cell membrane blebs and the appearance of autolysosomes and lipid droplets in all cell lines; KG1-a leukemia cells also showed the unique appearance of glycogen deposits. Our results reveal a novel mechanism of action for scorpion venom AMPs, activating a cascade of events leading to cell death through a programmed pyroptotic mechanism.

Study of the action mechanisms of Arnica montana effects on macrophages

Objective: To test the effect of Arnica montana (Arnica m.) on human macrophages. Method: The human monocytic leukaemia cell line THP-1 was cultured and differentiated in mature macrophages with PMA and other differentiating agents. Macrophages were exposed to Arnica m. homeopathic dilutions (2c, 3c, 5c, 9c and 15c) or Control solvent. Total RNA was isolated and sequenced to perform quantitative evaluation. Results: Screening sorted out with a list of 20 genes that were significantly changed by Arnica m. 2c treatment: 7 up-regulated and 13 down-regulated. Most notably, a clearly up-regulated function concerned the proteinaceous extracellular matrix (ECM), including genes HSPG2, FBN2, FN1 (p

Antioxidant and cytotoxic activities of Artemisia monosperma L. and Tamarix aphylla L. essential oils

Essential (volatile) oil from leaves of Artemisia monosperma L. belonging to family Asteraceae, and aerial parts of Tamarix aphylla L. (Athel) belonging to family Tamaricaceae were collected from the desert of Ha'il region, northern region of Saudi Arabia, hydro distilled by Clevenger apparatus and analysed by means of GC-MS techniques. Antioxidant activities of essential oils of A. monosperma and T. aphylla compared with ascorbic acid and butylated hydroxytoluene (BHT) as reference antioxidant compound were determined by method of DPPH radical scavenging assay and ABTS assay. In vitro screening of potential cytotoxicity of essential oils was also evaluated against human promyelocytic leukaemia cell lines (HL60 and NB4). The GC/MS analysis of A. monosperma essential oil resulted in identification of 61 components predominated mainly by β-Pinene as principal component (29.87%) and T. aphylla resulted in identification of 37 components of essential oil predominated mainly by 6,10,14- trimethyl-2-pentadecanone (21.43%) as principal component. Antioxidant activity as 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and 2,2 -azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) increased with increasing essential oil concentrations of A. monosperma and T. aphylla (25, 50, 75, 100 and 200 μg mL-1). The most pronounced increases detected in the high concentrations of the two essential oils. Biologically, essential oil extracts exhibited cytotoxicity effects in dose dependent manner against human promyelocytic leukaemia cell lines (HL60 and NB4). In conclusion, A. monosperma and T. aphylla essential oils could be valuable source for cytotoxic agents with high safety and selective cytotoxicity profiles.

Structural and mechanistic insight into DNA bending by antitumour calicheamicins

Among the class of enediyne antibiotics endowed with potent antitumour activities, the calicheamicin derivative known as ozogamicin is selectively targeted to several leukaemia cell types by means of tailor-made immunoconjugates....