4-amino-2-phenyl-6-(p-fluorophenyl)-5-carbonitrile-pyrimidine-bis-substituted-loaded liposomes as promising system for cancer treatment.

The aim of the present study was to perform in vitro and in vivo assessments of the antineoplastic action of 4-amino-pyrimidine encapsulated in liposomes. Liposomes were prepared and characterized for particle size and drug encapsulation and submitted to long-term stability tests. Cytotoxicity assays were performed in HeLa cells. Antineoplastic activity was investigated using the experimental sarcoma 180 tumor in Swiss albino mice. Encapsulation efficiency was 82.93 ± 0.04% and no significant changes were found with respect to particle size or pH after centrifugation and mechanical agitation tests. The in vitro results at concentration of 20 µg/mL indicated a considerable reduction in cell viability after treatment with encapsulated pyrimidine (75.91%). The in vivo assays using the compounds in encapsulated and free forms and 5-fluorouracil achieved tumor inhibition rates of 66.47 ± 26.8%, 50.46 ± 16.24% and 14.47 ± 9.22%, respectively. Mitotic counts demonstrated a greater reduction in the number of mitoses in animals treated with liposomal pyrimidine (32.15%) compared to those treated with the pyrimidine free (87.69%) and 5-fluorouracil (71.39%). This study demonstrated that the development of liposome formulations containing 4-amino-pyrimidine is a promising alternative for overcoming limitations related to the toxicity of current cancer treatment, ensuring greater therapeutic efficacy.

Chemical composition and biological activities of the essential oils from Vitex-agnus castus, Ocimum campechianum and Ocimum carnosum.

The essential oils obtained by hydrodistillation from fresh leaves of Vitex agnus-castus and Ocimum campechianum, and from fresh inflorescences of Ocimum carnosum were analysed by GC-FID and GC-MS. The major components of V. agnus-castus essential oil were identified as 1,8-cineole (47.9%), terpinyl α-acetate (11.6%), sabinene (11.2%) and caryophyllene oxide (9.7%), while in the O. campechianum essential oil were eugenol (72.1%), ß-elemene (6.8%), (E)-caryophyllene (6.4%) and bicyclogermacrene (5.2%). Linalool (79.0%), α-epi-cadinol (5.4%), terpinen-4-ol (3.2%) and 1,8-cineole (2.8%) were the major constituents in the O. carnosum essential oil. The essential oils were subsequently evaluated for their larvicidal and cytotoxic activities. Larval bioassay against Aedes aegypti of V. agnus-castus, O. campechianum and O. carnosum essential oils showed LC50 values of 97.55 ± 0.35, 81.45 ± 0.35 and 109.49 ± 0.35 µg/mL, respectively. The in vitro cytotoxic activities of the essential oils has been evaluated on breast adenocarcinoma (MCF-7), lung carcinoma (NCI-H292), pro-myelocytic leukemia (HL-60), and cervical adenocarcinoma (HEP-2) human cell lines, and pro-myelocytic leukemia cells lines (HL-60) were found to be the most sensitive to all the essential oils tested than the others. This is the first report on larvicidal and cytotoxic activities of these essential oils.

Synthesis, anti-proliferative activity, theoretical and 1H NMR experimental studies of Morita-Baylis-Hillman adducts from isatin derivatives.

Quaternary or spirocyclic 3-substituted-3-hydroxy-2-oxindole is considered a privileged scaffold. In other words, it is a molecular core present on several compounds with a wide spectrum of biological activities. Among its precursors, activated ketones (isatin nucleus) can be used as interesting starting points to Morita-Baylis-Hillman adducts derivatives, a class of compounds with good cytotoxic potential. In this paper, we present the synthesis, anti-proliferative activity against lung cancer cell line and a theoretical conformational study of 21 of Morita-Baylis-Hillman adducts from isatin derivatives, by DFT quantum chemical calculations, followed by a SAR and QSAR analysis. Besides, an efficient synthetic protocol and good biological activity profile were highlighted interesting observations about 1H NMR experimental spectra, molecular modeling results and crystallographic data available.

Structure-based design, synthesis and antitumoral evaluation of enulosides.

Enulosides, carbohydrate derivatives containing an α,ß-unsaturated carbonyl unit, were designed and obtained in high yields and isomeric purity. All synthesized compounds exhibited antitumoral activity in micromolar range against four tested tumor cells lines, being the best results observed for HL-60 cells. These compounds open new possibilities to prepare an array of more active, site-specific or selective antitumor agents. 2016 Elsevier Ltd. All rights reserved.

New Cytotoxic Bibenzyl and Other Constituents from Bauhinia ungulata L. (Fabaceae).

A new bibenzyl, 2'-hydroxy-3,5-dimethoxy-4-methylbibenzyl (1) and four known compounds identified as 2'-hydroxy-3,5-dimethoxybibenzyl (2), liquiritigenin (3), guibourtinidol (4) and fisetinidol (5) were isolated from the roots of Bauhinia ungulata L. Phytochemical investigations of the stems of B. ungulata led to the isolation of the known compounds identified as liquiritigenin (3), guibourtinidol (4), fisetinidol (5), taraxerol (6), betulinic acid (7), taraxerone (8), glutinol (9), a mixture of sitosterol (10) and stigmasterol (11), pacharin (12), naringenin (13) and eriodictyol (14). The structures of these compounds were elucidated on the basis of their spectral data (IR, MS, 1D- and 2D-NMR). The cytotoxicity of the bibenzyl 1 has been evaluated against four human cancer cell lines, showing the IC50 values of 4.3 and 6.5 µg ml-1 against pro-myelocytic leukemia (HL-60) and cervical adenocarcinoma (HEP-2) cell lines, respectively. This article also registers for the first time the 13 C-NMR data of the known bibenzyl 2.

Stereoselective synthesis and antitumoral activity of Z-enyne pseudoglycosides.

An efficient approach for the synthesis of Z-1,3-enynes based on the coupling reaction of Z-vinyl tellurides and alkynes containing a pseudoglycoside moiety is described. The products were obtained in good yields via a stereoselective way. Preliminary screening against three tumor cell lines indicated that the synthesized compounds are promising intermediates for the synthesis of an array of more potent target structures.