Synthesis and Cytotoxic Activity of Novel Betulin Derivatives Containing Hydrazide-Hydrazone Moieties

A series of novel betulin derivatives containing hydrazide-hydrazone moieties were synthesized. All compounds were evaluated for their cytotoxicity against four human carcinoma cell lines (HepG2, A549, MCF-7 and HCT-116) and a normal human gastric epithelial cell line (GES-1). Among them, compound 6i was the most potent against HepG2 and MCF-7 cell lines, with IC50 values of 9.27 and 8.87 μM, respectively. The results suggest that the incorporation of a hydrazide-hydrazone side chain at the C-28 position of betulin is beneficial for compounds to display significant cytotoxicity. Compound 6i may be used as a promising skeleton for antitumor agents with improved efficacy.

Crystallization, Luminescence and Cytocompatibility of Hexagonal Calcium Doped Terbium Phosphate Hydrate Nanoparticles

Luminescent lanthanide-containing biocompatible nanosystems represent promising candidates as nanoplatforms for bioimaging applications. Herein, citrate-functionalized calcium-doped terbium phosphate hydrate nanophosphors of the rhabdophane type were prepared at different synthesis times and different Ca2+/Tb3+ ratios by a bioinspired crystallization method consisting of thermal decomplexing of Ca2+/Tb3+/citrate/phosphate/carbonate solutions. Nanoparticles were characterized by XRD, TEM, SEM, HR-TEM, FTIR, Raman, Thermogravimetry, inductively coupled plasma spectroscopy, thermoanalysis, dynamic light scattering, electrophoretic mobility, and fluorescence spectroscopy. They displayed ill-defined isometric morphologies with sizes ≤50 nm, hydration number n ~ 0.9, tailored Ca2+ content (0.42–8.11 wt%), and long luminescent lifetimes (800–2600 µs). Their relative luminescence intensities in solid state are neither affected by Ca2+, citrate content, nor by maturation time for Ca2+ doping concentration in solution below 0.07 M Ca2+. Only at this doping concentration does the maturation time strongly affect this property, decreasing it. In aqueous suspensions, neither pH nor ionic strength nor temperature affect their luminescence properties. All the nanoparticles displayed high cytocompatibility on two human carcinoma cell lines and cell viability correlated positively with the amount of doping Ca2+. Thus, these nanocrystals represent promising new luminescent nanoprobes for potential biomedical applications and, if coupled with targeting and therapeutic moieties, they could be effective tools for theranostics.

Glycoalkaloids as medicinal agents from callus and regenerated plants of Solanum nigrum var. judaicum

The target of this study is production of glycoalkaloids from cultures of Solanum nigrum var. judaicum Besser. Further, to evaluate their therapeutic effects. S. nigrum var. judaicum leaves were implanted in MS media containing growth regulators for in vitro study. HPLC analyses were applied for qualitative and quantitative determination of glycoalkaloids. Cytotoxic effects against human carcinoma cell lines were evaluated. In addition, antiviral, antioxidant, anti-inflammatory and antiparasitic activities of the formed glycoalkaloids were estimated. HPLC data indicated the success of in vitro solasodine and solanidine glycosides production. Solasonine represented the highest concentration. Biological assays illustrated that obtained glycoalkaloids exhibited cytotoxic activity against human carcinoma cell lines that may be attributed to free radical scavenging activity (69.98%). Strong antiherps performance was observed (94%). In addition, the glycoalkaloids showed in vitro schistomicidal (IC50 76.4 ppm) and fasciolicidal (IC50 76.6 ppm) activities. In vivo anti-inflammatory assay revealed potent activity against carrageenan induced edema. Glycoalkaloids were formed 2-5 folds that of intact plant pointed to the efficiency of the cultures. The present findings referred to the pronounced biological performance of the produced glycoalkaloids including antiviral, cytotoxic anti-inflammatory and antiparasitic activities. Botanical derived medication from S. nigrum var. judaicum could be accomplished guided with the present data.

Scopularides Revisited: Molecular Networking Guided Exploration of Lipodepsipeptides in Australian Marine Fish Gastrointestinal Tract-Derived Fungi

Chemical analysis of a cultivation of an Australian Mugil mullet gastrointestinal tract (GIT) derived fungus, Scopulariopsis sp. CMB-F458, yielded the known lipodepsipeptides scopularides A (1) and B (2). A comparative global natural product social (GNPS) molecular networking analysis of ×63 co-isolated fungi, detected two additional fungi producing new scopularides, with Beauveria sp. CMB-F585 yielding scopularides C–G (3–7) and Scopulariopsis sp. CMB-F115 yielding scopularide H (8). Structures inclusive of absolute configurations were assigned by detailed spectroscopic and C3 Marfey’s analysis, together with X-ray analyses of 3 and 8, and biosynthetic considerations. Scopularides A–H (1–8) did not exhibit significant growth inhibitory activity against a selection of Gram positive (+ve) and negative (−ve) bacteria, a fungus, or a panel of three human carcinoma cell lines.

Synthesis and Anti-Tumor Activity Evaluation of Novel 7-Fluoro-4-(1- Piperazinyl) Quinolines

Background: Three series of new 7-fluoro-4-(1-piperazinyl) quinolines (I1~I6, II1~II2 and IV1~IV4) were synthesized. Their anti-tumor activity was evaluated in vitro against three human carcinoma cell lines, namely SGC-7901 cells, BEL-7402 cells and A549 cells expressing high levels of EGFR by Methyl Thiazolyl Terazolium (MTT) assay. Methods: Three series of quinoline derivatives were synthesized, characterized and evaluated for their in vitro anti-tumor activities. Results and Discussion: Structures of the newly synthesized compounds were confirmed by spectral analysis. The preliminary bioassay indicated that compounds I1, I10 and II1 exhibited better anti-tumor activity than the rest of the target compounds and gefitinib against A549 cell based assay, which demonstrated that compounds I1, I10 and II1 are potential agents for cancer therapy. Results suggested that the substitutes on piperazinyl influenced anti-tumor activities remarkably. Conclusion: These results are useful for discovering more potent novel anti-tumor compounds and further studies are ongoing.