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This study presents comparison of our recently formulated two compartmental model with General fractional derivative (GFD) and Korsmeyer–Peppas, Makoid–Banakar and Kopcha diffusion models. We have used our GFD model to study the release of gentamicin in poly (vinyl alcohol)/chitosan/gentamicin (PVA/CHI/Gent) hydrogel aimed for wound dressing in medical treatment of deep chronical wounds. The PVA/CHI/Gent hydrogel was prepared by physical cross linking of poly(vinyl alcohol)/chitosan dispersion using freezing-thawing method, and then was swollen for 48 h in gentamicin soluteion, at 37ºC. Different physicochemical (FTIR, SEM), mechanical and biological (cytotoxicity, antibacterial activity) properties have been determined. The concentration of released gentamicin was determined using a high-performance liquid chromatography (HPLC) coupled with mass spectrometry (MS). The ratio between concentration of released gentamicin and initial concentration of gentamicin in the hydrogel was monitored for the prolonged time period in order to obtain gentamicin release profile. It was proven that our novel diffusion GFD model better fitted to experimental data then other models, and enabled the determination of diffusion coefficient precisely for the entire time period.

Four novel conformationally restricted (–)-muricatacin analogues, bearing a methoxy group at the C-5 position and with an alkoxymethyl group аs the C-7 side chain, have been synthesised and their in vitro antiproliferative activity was evaluated against a panel of seven human tumour cell lines, as well as a single normal cell line. All analogues (9–12) showed diverse antiproliferative effects against all tested human malignant cell lines, but were devoid of any significant cytotoxicity towards the normal foetal lung fibroblasts (MRC-5). A structure–activity relationship study reveals that the introduction of tetrahydrofuran ring, the replacement of C-8 methylene group in the side chain of muricatacin analogues with the O-8 ether functionality, as well as the length of side chain may be beneficial for the antiproliferative effects of these lactones. All novel analogues were more potent than lead compound, (–)-muricatacin, against HL-60 cell line.

New thiazole hybrids were synthesized and evaluated for their in vitro cytotoxicity against a panel of human malignant cell lines. The key steps in the synthesis of hybrids 3–7 involved the initial condensation of appropriate aldononitriles with cysteine ethyl ester hydrochloride, followed by subsequent treatment of resulting thiazolines with diazabicycloundecene to form the thiazole ring. Bioisosteres 8 and 14 have been prepared after the stereoselective addition of 2-(trimethylsilyl)thiazole to the hemiacetals obtained by periodate cleavage of terminal diol functionality in the suitably protected d-glucose derivatives. The obtained analogues showed various antiproliferative activities in the cultures of several tumour cell lines. Hybrid 6 was the most potent in HeLa cells, exhibiting more than 10 and 4 times stronger activity than both leads 1 and 2, respectively. The most active compound in Raji cells was hybrid 12, which was nearly 2-fold more potent than the clinical antitumour drug doxorubicin. All analogues were more potent in A549 cells with respect to lead 1, while compounds 6 and 7 were slightly more active than doxorubicin. Preliminary structure–activity relationship analysis revealed that the presence of a cinnamate group at the C-3 position in analogues of type 7 increases the activity of resulting molecular hybrids.

α-Tricalcium phosphate/fluorapatite (α-TCP/FAp) mixed powders were prepared in order to obtain dental root canal filling cements. Different liquids for cement pastes have been investigated and the most suitable one for obtaining rheologically optimal pastes was chosen for further analysis. Morphological changes in the cement materials as a consequence of the formation of hydroxyapatite (HAp) after the immersion in a simulated body fluid (SBF), an influence on the cell viability, and final success of the filling were investigated by field emission scanning electron microscopy. Treatment of the α-TCP/FAp mixtures in SBF at 37°C resulted in a complete transformation of α-TCP into HAp after 10 days, while the exposure of MRC-5 human and L929 animal fibroblast cells to the cement showed complete absence of cytotoxicity. The root canal of an extracted tooth was filled with the α-TCP/FAp cement containing 5 wt.% of FAp and relatively strong adhesion between the cement and dentine was observed after 48h. The same cement material was immersed during 10 days in SBF and after that both human and animal fibroblast cells during in vitro MTT tests showed higher cell viability compared to the control sample. These findings lead to a conclusion that the α-TCP/FAp based cement demonstrates potential for further development towards dental cement application.

A dicarboxylato-diamide-type compound 2,2'-[(1,2-dioxoethane-1,2- -diyl)diimino]dibenzoic acid (H4obbz) (1) was synthesized and characterized. The crystal structure of K2H2obbz·2H2O (2) was determined by X-ray diffracttion analysis. The cytotoxic activities of the compounds were tested against four different cancer cell lines MCF-7, A549, HT-29, HeLa and a human normal cell line MRC-5. The results indicate reasonable dose-dependent cytotoxicity of the ligands that show selectivity against the tested carcinoma and healthy cell lines. Flow cytometric analysis and fluorescence microscopy showed that the most active compound, H4obbz, induced apoptosis and G0/G1 cell cycle arrest, indicating blockage of DNA synthesis as a possible mechanism that triggers apoptosis. Docking and molecular dynamics simulations gave similar responses regarding interactions (binding) between their ligands and chaperon Grp78. The MMGBSA determined ΔG binding energies were in the range from –104 to –140 kJ mol-1.

Steroids are good candidates for drug development, thanks to their low general toxicity and possibility for structure modifications connected with change of their activity. Several 16,17-secoandrost-4-ene-16,17a-dinitrile compounds were synthesized and screened for anticancer effect previously, including 6-oxo and 6-hydroxyimino compounds. This research is continued with the attempts for different synthetic strategy and evaluation of anticancer effect mechanism. Synthesis of 3-hydroxyimino compounds was successful, but inseparable mix of isomers was excluded from biological tests. Tested secodinitriles expressed cytotoxic effect on HeLa cervix cancer cells as a model system, with submicromolar to molar IC50 values, where 6-substituted derivatives were more effective. After 72 h treatment with equitoxic concentrations equal IC50 values of test compounds the mechanism of this effect was studied using flow cytometry and specific fluorescent dyes. Modest change in both G0/G1 and G2/M resting phases and change in mitochondrial membrane potential were noticed, while the most pronounced effect was apoptosis induction. Total apoptosis was in range 50.72–58.31 % in all cell samples treated with secodinitriles, compared to 7.44 % in control samples. Total percent of dead cells, including both apoptotic and necrotic, ranged from 55.24 to 65.34 %, compared to 10.68 % in control. Selectivity towards cancer cells is very important feature of these compounds indicating their potential use as lead compounds in the drug development for the treatment of cancers of steroid hormone-dependent tissues.

Several (+)-goniofufurone analogues with simplified structures were designed, synthesized and evaluated for their in vitro antitumour activity, against a panel of human tumour cell lines. Dephenylated compounds 2 and 3 demonstrated remarkable antitumour activities, in the cultures of K562 and Raji cells with IC50 values in the range of 3.0–9.3 nM. Each of goniofufurone analogues lacking the tetrahydrofuran ring (4, 5 and 6) strongly inhibited the growth of at least one malignant cell line, with IC50 values in the range of 11-30 nM. Brief structure–activity relationship (SAR) analysis showed that the simplified goniofufurone analogues, designed by removing the phenyl group from C-7, or by opening the THF ring, could show stronger antiproliferative effects compared to control molecules. It is noticeable that analogues 2–8 are completely inactive with respect to the normal MRC-5 cell line. These findings, together with their potent antitumour activities, provide a suitable basis for the development of new and selective antitumour drugs.

Ionic liquids (ILs) are well known for their physicochemical properties that recommend them for many purposes. However, many ILs are not environmentally friendly. Bearing these facts in mind, a series of imidazoliumand salicylate-based ILs with low general toxicity were designed and their pharmacological potential studied. Herein, their antiproliferative effect against human cancer cell lines and antimicrobial activity on selected Gram-positive and Gram-negative bacteria and Candida strains are presented. ILs with 1-butyl- -3-methylimidazolium or imidazolium cation (IL 1 and compound 5), with the lowest dipole moments and highest lipophilicity, exerted highest cytotoxicity against colon and/or lung cancer cells, manifesting high selectivity to the normal cells. The most non-polar IL with the 1-butyl-3-methylimidazolium cation expressed the strongest anticancer potential, but it was also toxic against normal cells, although its cytotoxicity was less than the cytotoxic effect of commercially used chemotherapeutic agents. The same compounds, IL 1 and compound 5, expressed modest effect on the bacterial strain that causes serious lung diseases and pulmonary infections (Staphylococcus aureus) or which are included in colon cancer formation (Esherichia coli and Enterococcus faecalis). Salicylate itself was toxic against lung cancer cell line A549 and affected some Candida strains. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 172012 and Grant no. 172058]

Divergent syntheses of novel (–)-goniofufurone mimics with an alkoxymethyl group as the side chain have been accomplished from D-glucose in nine synthetic steps and in overall yields 6.7–8.7 %. Their in vitro antiproliferative activity was evaluated against eight human tumour cell lines as well as a single normal cell line. All analogues demonstrated powerful to good antiproliferative effects toward all malignant cell lines under evaluation. Against the HL-60 cell line, all mimics showed increased activities being 27- to 1604-fold more potent than the lead compound, (–)-goniofufurone. Remarkably, the majority of synthesized analogues displayed higher or similar activity to the commercial antitumour agent doxorubicin (DOX) against A549 cell line. The most potent compound exhibited 196-fold stronger cytotoxicity than DOX in the culture of this cell line.

Background/Aim. There is limited published evidence on the cytotoxicity of 3D printed polymer materials for dentistry applications, despite that they are now being widely used in medicine. Stereolithography (SLA) is one of the foremost 3D processes used in 3D printing, yet there are only a small number of resin materials reported to be suitable for medical applications. The aim of this study was to investigate, in vitro, the cytotoxic effect of the 3D printed resin in order to establish the suitability for its usage in dentistry and related medical applications such as surgical dental guides, occlusal splits and orthodontic devices. Methods. To examine the cytotoxicity of the 3D printed polymer-based epoxy resin, Accura® ClearVue™ (3D-Systems, USA), two cell cultures were used: mouse fibroblasts L929 and human lung fibroblasts MRC-5. Cell viability was determined by Mosmann's colorimetric (MTT) test and the agar diffusion test (ADT). Results. Direct contact of the tested material with ADT test showed nontoxic effects of tested material in any cell culture. The tested material showed no cytotoxic effect after 3 days of extraction of the eluate by MTT test, but mild cytotoxic effect after 5, 7 and 21 days on both cell lines. The cytotoxicity increased with increasing the time of the eluate extraction. Conclusion. 3D printed polymer-based epoxy resin, Accura® ClearVue™ (3D-Systems, USA) is considered appropriate for making surgical dental implant guides according to the cytotoxic behavior. According to the mild level of cytotoxicity after the longer extraction periods, there is a need for further evaluation of biocompatibility for its application for occlusal splints and orthodontic devices. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. TR 35020: Research and development of modeling methods and approaches in manufacturing of dental recoveries with the application of modern technologies and computer aided systems]