Comprehensive evaluation of carboxylated nanodiamond as a topical drug delivery system.

The best strategy in the development of topical drug delivery systems may be to facilitate the permeation of drugs without any harmful effects, while staying on the skin surface and maintaining stability of the system. Nanodiamonds (NDs) play a key role with their excellent physicochemical properties, including high biocompatibility, physical adsorption, reactive oxygen species (ROS) scavenging capability, and photostabilizing activity. Z-average sizes of carboxylated ND (ND-COOH) agglutinate decreased significantly as the pH increased. Fluorescein-conjugated ND was observed only on the stratum corneum, and no sample diffused into the dermal layer even after 48 hours. Moreover, ND-COOH and ND-COOH/eugenol complex did not show significant toxic effects on murine macrophage cells. ND improved in vitro skin permeation >50% acting as a "drug reservoir" to maintain a high drug concentration in the donor chamber, which was supported by quartz crystal microbalance results. Moreover, ND-COOH could adsorb a drug amount equivalent to 80% of its own weight. A photostability study showed that ND-COOH increased the photostability ~47% with regard to rate constant of the eugenol itself. A significant decrease in ROS was observed in the ND-COOH and ND-COOH/eugenol complex compared with the negative control during intracellular ROS assay. Moreover, ROS and cupric reducing antioxidant capacity evaluation showed that ND-COOH had synergistic effects of antioxidation with eugenol. Therefore, ND-COOH could be used as an excellent topical drug delivery system with improved permeability, higher stability, and minimized safety issue.

Synthesis of daumone derivatives and their antiangiogenic activities on chorioallantoic membrane.

Daumone, a dauer-inducing pheromone and a series of lipid derivatives were synthesized from daumone to investigate structure-activity trends. Lipid derivatives demonstrated potent in vivo antiangiogenic activity on the chorioallantoic membrane, which exceeded that of fumagillin and thalidomide as reference agents. Among the 11 synthetic compounds tested, new derivatives 3, 11 and 13 showed the most potent antiangiogenic activity, which was twice that of fumagillin and thalidomide, replacing these as the most potent known antiangiogenic agents.

Synthesis and anticancer activity of novel deoxoartemisinin-glycolipid hybrids.

The practical synthesis and anticancer activity of novel deoxoartemisinin-glycolipid hybrids, which incorporate two drugs into a single molecule and can impact multiple targets simultaneously are presented. These hybrids exhibited potent in vitro anticancer activity against several human cancer cell lines. The deoxoartemisinin-glycolipid hybrids generally demonstrated better anticancer activity than either artemisinin or daumone alone and cisplatin.

Total synthesis of flocoumafen via knoevenagel condensation and intramolecular ring cyclization: general access to natural products.

The total synthesis and structure determination of cis- and trans-flocoumafen was described. The key synthetic steps involve Knoevenagel condensation with p-methoxybenzaldehyde, in situ decarboxylation and intramolecular ring cyclization to construct the tetralone skeleton. Stereospecific reduction of the O-alkylated ketone 13 afforded good yield of precusor alcohol 5. Final coupling of alcohol 5 with 4-hydroxy-coumarin yielded flocoumafen (1). Separation and structure determination of cis- and trans-flocoumafen through 2D NMR analyses-assisted computer simulation techniques for the evaluation of anticoagulant activities are reported for the first time. This method is useful for generating the core tetralone skeleton of 4-hydroxycoumarin derivatives and provides a generalized access to various warfarin type anticoagulants.

Discovery of artemisinin-glycolipid hybrids as anti-oral cancer agents.

Novel artemisinin-glycolipid hybrids were directly synthesized from 12ß (C-C)-type deoxoartemisinin and glycolipid and exhibited exceptional in vitro anticancer activity, particularly against the oral carcinoma cancer cell lines, respectively. The artemisinin-glycolipid hybrids, with effective concentrations under 20 µM, demonstrated better anticancer activity than either artemisinin or glycolipid alone and showed five times more anti-oral cancer activity than either cisplatin or paclitaxel.

Synthesis of a dual-labeled probe of dimethyl lithospermate B with photochemical and fluorescent properties.

Dimethyl lithosermate B (DLB) is a highly potent natural antioxidant and antidiabetic polyphenol with unknown mode of action. To determine its cellular targets, a photochemical and fluorescent dimethyl lithopermate B probe was designed and efficiently synthesized. The dual-labeled chemical probe for biological application was evaluated by UV and fluorescence to determine its electrochemical absorption and emission properties. This probe could be valuable for investigating ligand-protein interactions and subcellular localization.

Concise synthesis and antiangiogenic activity of artemisinin-glycolipid hybrids on chorioallantoic membranes.

Novel hybrids of non acetal and acetal-type derivatives at C-12 of artemisinin and glycolipids were synthesized via efficient coupling reactions. Some of these hybrids showed potent in vivo antiangiogenic activity on the chorioallantoic membrane (CAM) that was higher than or comparable to those of fumagillin and thalidomide at a concentration of 2.5 nmol.