Caffeine-Containing Emulsion: Influence of the HLB and Mixing Proportions, the Oil's Chemical Composition, and the Existence of Caffeine on Emulsion Properties.

This study employs a low-energy emulsification method to prepare caffeine-containing emulsions, denoted as Caf-EM. Three different oils, including coconut, sesame, and grape seed oils, are utilized along with the surfactants Span 80 and Tween 80. We investigate the influence of various factors, including (i) the hydrophilic-lipophilic balance (HLB) and surfactant ratio, (ii) the chemical composition of the oils, and (iii) the presence of caffeine, on the stability and size of emulsions. The results indicate that the HLB value and surfactant ratio are the most crucial factors affecting the emulsions' stability. The most stable Caf-EM formulation is achieved by combining mixed surfactants of Span 80 and Tween 80 with an optimal HLB value of 6.4 at a concentration of 15% (S15 to 6.4) across all oil types. This specific ratio also leads to significantly smaller emulsion droplet sizes than other ratios and is the only ratio that produces stable emulsions even without caffeine (denoted as EM). Notably, formulation S15-6.4 additionally causes a phase inversion from oil-in-water (O/W) to water-in-oil (W/O). Furthermore, the presence of caffeine in the water phase contributes to the formation of smaller and more stable emulsions. The particle size of Caf-EM is approximately 1.5 times smaller than that of EM. Regarding the oil's chemical composition, while there is a discernible trend in emulsion droplet size (coconut oil > grape seed oil > sesame oil), the differences within this sequence are insignificant, suggesting that the oil's chemical composition does not have a pronounced effect.

One-Pot Synthesis and Evaluation of Antioxidative Stress and Anticancer Properties of an Active Chromone Derivative.

Chromones are the structural building blocks of several natural flavonoids. The synthesis of chromones, which contain a hydroxy group on the ring, presents some challenges. We used the one-pot method to synthesize ten chromone derivatives and two related compounds using modified Baker-Venkataraman reactions. The structures were confirmed using FT-IR, 1H NMR, 13C NMR, and HRMS. The in vitro antioxidant assay revealed that compounds 2e, 2f, 2j, and 3i had potent antioxidant activity and that all these synthesized compounds, except those containing nitro groups, were harmless to normal cells. In addition, compounds 2b, 2d, 2e, 2f, 2g, 2i, and 2j had anticancer activity. Compounds 2f and 2j were used to investigate the mechanism of anticancer activity. Both 2f and 2j induced a slightly early apoptotic effect but significantly impacted the S phase in the cell cycle. The effect on cell invasion indicates that both compounds significantly inhibited the growth of cervical cancer cells. A chromone scaffold possesses effective chemoprotective and antioxidant properties, making it a promising candidate for antioxidant and future cancer treatments.

Formulation optimization of sterilized xanthones-loaded nanoemulgels and evaluation of their wound healing activities.

Xanthones (XTs) are bioactive compounds found in mangosteen trees (Garcinia mangostana Linn.). They are used as an active ingredient in various health products. However, there is a lack of data of their application in wound healing. In particular, the topical products of XTs for wound healing; they should be sterilized to minimize the risks of wound infection from contaminated microorganisms. This study thus aimed to optimize the formulation of sterilized XTs-loaded nanoemulgel (XTs-NE-G) and to investigate their wound healing activities. The XTs-NE-Gs were prepared by mixing various gels containing sodium alginate (Alg) and Pluronic F127 (F127) into a XTs-nanoemulsion (NE) concentrate according to the face-centered central composite design. The results showed that the optimized XTs-NE-G was A5-F3 containing 5% w/w Alg and 3% w/w F127. It enhanced the proliferation-, migration rates of skin fibroblasts (HFF-1 cells) with an optimal viscosity. After blending the XTs-NE concentrate and the gel that was previously sterilized by a membrane filtration and an autoclaving technique, respectively, the sterilized A5-F3 was obtained. The sterilized A5-F3 still had effective bioactivities towards the HFF-1 cells. It promoted re-epithelialization, collagen deposition and inflammation suppression in the mice' wounds. It could thus be accepted for further investigation in clinical studies.

Identification of novel aza-analogs of TN-16 as disrupters of microtubule dynamics through a multicomponent reaction.

Despite novel biological targets emerging at an impressive rate for anticancer therapy, antitubulin drugs remain the backbone of numerous oncological protocols and their efficacy has been demonstrated in a wide variety of adult and pediatric cancers. In the present contribution, we set to develop analogs of a potent but neglected antitubulin agent, TN-16, originally discovered via modification of tenuazonic acid (3-acetyl-5-sec-butyltetramic acid). To this extent, we developed a novel multicomponent reaction to prepare TN-16, and then we applied the same reaction for the synthesis of aza-analogs. In brief, we prepared a library of 62 novel compounds, and three of these retained nanomolar potencies. TN-16 and the active analogs are cytotoxic on cancer cell lines and, as expected from antitubulin agents, induce G2/M cell cycle arrest. These agents lead to a disruption of the microtubules and an increase in α-tubulin acetylation and affect in vitro polymerization, although they have a lesser effect in cellular tubulin polymerization assays.

Effect of electrical discharge plasma on cytotoxicity against cancer cells of N,O-carboxymethyl chitosan-stabilized gold nanoparticles.

Electrical discharge plasma in a liquid phase can generate reactive species, e.g. hydroxyl radical, leading to rapid reactions including degradation of biopolymers. In this study, the effect of plasma treatment time on physical properties and cytotoxicity against cancer cells of N,O-carboxymethyl chitosan-stabilized gold nanoparticles (CMC-AuNPs) was investigated. AuNPs were synthesized by chemical reduction of HAuCl4 in 2 % CMC solution to obtain CMC-AuNPs, before being subjected to the plasma treatment. Results showed that the plasma treatment not only led to the reduction of hydrodynamic diameters of CMC-AuNPs from 400 nm to less than 100 nm by the plasma-induced degradation of CMC but also provided the narrow size distribution of AuNPs having diameters in the range of 2-50 nm, that were existing in CMC-AuNPs. In addition, the plasma-treated CMC-AuNPs could significantly reduce the percentage of cell viability of breast cancer cells by approximately 80 % compared to the original CMC and CMC-AuNPs.

Cytotoxicity against cancer cells of chitosan oligosaccharides prepared from chitosan powder degraded by electrical discharge plasma.

Chitosan oligosaccharides, which obtain from degradation of chitosan, possess some interesting molecular weight-dependent biological properties, especially anticancer activity. Therefore, the conversion of chitosan to chitosan oligosaccharides with specific molecular weight has been continuously investigated in order to find effective strategies that can achieve both economic feasibility and environmental concerns. In this study, a novel process was developed to heterogeneously degrade chitosan powder by highly active species generated by electrical discharge plasma in a dilute salt solution (0.02 M) without the addition of other chemicals. The degradation rate obtained from the proposed process was comparable to that obtained from some other methods with the addition of acids and oxidizing agents. Separation of the water-soluble degraded products containing chitosan oligosaccharides from the reaction solution was simply done by filtration. The obtained chitosan oligosaccharides were further evaluated for an influence of their molecular weights on cytotoxicity against cancer cells and the selectivity toward cancer and normal cells.

Enhanced degradation of chitosan by applying plasma treatment in combination with oxidizing agents for potential use as an anticancer agent.

Solution plasma (SP) treatment in combination with oxidizing agents, i.e., hydrogen peroxide (H2O2), potassium persulfate (K2S2O8) and sodium nitrite (NaNO2) were adopted to chitosan degradation in order to achieve fast degradation rate, low chemicals used and high yield of low-molecular-weight chitosan and chitooligosaccharide (COS). Among the studied oxidizing agents, H2O2 was found to be the best choice in terms of appreciable molecular weight reduction without major change in chemical structure of the degraded products of chitosan. By the combination with SP treatment, dilute solution of H2O2 (4-60mM) was required for effective degradation of chitosan. The combination of SP treatment and dilute solution of H2O2 (60mM) resulted in the great reduction of molecular weight of chitosan and water-soluble chitosan was obtained as a major product. The resulting water-soluble chitosan was precipitated to obtain COS. An inhibitory effect against cervical cancer cell line (HeLa cells) of COS was also examined.

Iridium-catalyzed cycloaddition of azides and 1-bromoalkynes at room temperature.

Iridium dimer complexes were found to catalyze the [3 + 2] cycloaddition reaction of azides with bromoalkynes, yielding 1,5-disubstituted 4-bromo-1,2,3-triazoles in reasonable to excellent yields under mild conditions. The reaction offers a direct route to new 1,4,5-trisubstituted triazoles.

Parallel synthesis of "click" chalcones as antitubulin agents.

It has been shown that some chalcones are able to inhibit tubulin polymerization, giving cytotoxicity and destruction of tumoral vasculature. A library of 180 novel chalcone analogs has been synthesized via click chemistry and screened for their cytotoxicity and tubulin assembly inhibition. 10 out 180 click chalcones displayed low micromolar cytotoxicity but only compound Nf depicted antitubulin activity. While Nf displayed only micromolar potency this result shows click-chalcones may be anti-tubulin agents and validate this strategy to search for novel active chemical entities.

Identification of novel antitubulin agents by using a virtual screening approach based on a 7-point pharmacophore model of the tubulin colchi-site.

Tubulin inhibition represents an established target in the field of anticancer research, and over the last 20 years, an intensive search for new antimicrotubule agents has occurred. Indeed, in silico models have been presented that might aid the discovery of novel agents. Among these, a 7-point pharmacophore model has been recently proposed. As a formal proof of this model, we carried out a ligand-based virtual screening on the colchicine-binding site. In vitro testing demonstrated that two compounds displayed a cytotoxic profile on neuroblastoma cancer cells (SH-SY5H) and one had an antitubulinic profile.

Regioselective Suzuki coupling of dihaloheteroaromatic compounds as a rapid strategy to synthesize potent rigid combretastatin analogues.

Combretastatin A-4 (CA-4) is a potent tubulin depolymerizing agent able to inhibit tumor growth and with antivascular effects. Although it is in clinical trials, the search for novel analogues that may display better/different features is still ongoing. In this manuscript we describe the synthesis of novel constrained analogues of CA-4 obtained in only two synthetic steps exploiting a regioselective Suzuki coupling of dihalogenated heteroaromatic and alicyclic compounds. All the compounds synthesized have been evaluated for cytotoxicity and for their ability to inhibit tubulin assembly. One of them, 38, displayed low nanomolar cytotoxicity and proved to have a pharmacodynamic profile similar to that of CA-4 and a better pharmacokinetic profile, but most important of all, this synthetic strategy may pave the way for the easy and rapid generation of novel rigid analogues of combretastatins.