Cytotoxic and Apoptotic Activity of Aglaforbesin Derivative Isolated from Aglaia loheri Merr. on HCT116 Human Colorectal Cancer Cells.

BACKGROUND: The genus Aglaia (Meliaceae) is an established source of many anticancer compounds. The study evaluated the leaf extracts of Aglaia loheri, a tree native to the Philippines, as potential source of anticancer compounds. METHODS: Using bioassay-guided fractionation, A. loheri leaf extract was subjected to various chromatographic techniques and step-wise application of MTT assay on human colorectal carcinoma cells, HCT116, to determine the cytotoxic fractions. The most cytotoxic HPLC isolate was structurally identified using 1D and 2D NMR and its apoptotic effect was assessed by JC-1 staining, caspase 3/7 assay and TUNEL assay. RESULTS: After stepwise chromatography fractionation, an HPLC isolate, structurally identified as aglaforbesin derivative (AFD), demonstrated potent cytotoxicity against HCT116. AFD exhibited strong toxicity (IC50 = 1.13 ±0.07 µg/mL) and high selectivity on HCT116 than normal human kidney cells (HK-2). AFD-induced toxicity to HCT116 is possibly through the stimulation of the apoptotic signaling pathway via caspase 3/7 activation and DNA fragmentation independent of mitochondrial membrane depolarization. CONCLUSION: AFD exhibited selective cytotoxicity and apoptotic activity to HCT116 and could be further developed as anticancer drug lead.

Ultrasound-assisted depolymerization of kappa-carrageenan and characterization of degradation product.

Degradation of polysaccharides to afford low-molecular-weight oligosaccharides have been shown to produce new bioactivities that are not present in the starting material. The simplicity of ultrasonic treatment in the degradation of a polysaccharide, such as κ-carrageenan, offers practical advantage in producing degraded products with lower molecular weight that may have new interesting potential activities. This study embarked on investigating the effects in molecular weights and structural changes of κ-carrageenan under varying ultrasonic conditions. Molecular weight (MW) monitoring of ultrasonically-treated κ-carrageenan at various conditions were done by gel permeation chromatography. The product formed using the optimized condition was characterized using FTIR and NMR. The decrease in MW has been shown to be dependent on low concentration (5.0 mg mL-1), high amplitude (85%), and long treatment time (180 mins) to afford a degraded κ-carrageenan with average molecular weight (AMW) of 41,864 Da, which is a 96.33% reduction from the raw sample with initial AMW of 1,139,927 Da. Structural analysis reveals that most of the peaks of the raw κ-carrageenan was retained with minor change. 1D and 2D NMR analyses showed that the sonic process afforded a product where the sulfate group at the G4S-4 position was cleaved forming a methylene in the G4S ring. The results would be useful in the structure-activity relationship of κ-carrageenan oligosaccharides and in understanding the effect in the various potential applications of degraded κ-carrageenan.

Regenerable Acidity of Graphene Oxide in Promoting Multicomponent Organic Synthesis.

The Brønsted acidity of graphene oxide (GO) materials has shown promising activity in organic synthesis. However, roles and functionality of Lewis acid sites remain elusive. Herein, we reported a carbocatalytic approach utilizing both Brønsted and Lewis acid sites in GOs as heterogeneous promoters in a series of multicomponent synthesis of triazoloquinazolinone compounds. The GOs possessing the highest degree of oxidation, also having the highest amounts of Lewis acid sites, enable optimal yields (up to 95%) under mild and non-toxic reaction conditions (85 °C in EtOH). The results of FT-IR spectroscopy, temperature-programed decomposition mass spectrometry, and X-ray photoelectron spectroscopy identified that the apparent Lewis acidity via basal plane epoxide ring opening, on top of the saturated Brønsted acidic carboxylic groups, is responsible for the enhanced carbocatalytic activities involving Knoevenagel condensation pathway. Recycled GO can be effectively regenerated to reach 97% activity of fresh GO, supporting the recognition of GO as pseudocatalyst in organic synthesis.