Synthesis and characterization of some palladium(ii) complexes and their potential biological activity

Otkriće antitumorskih osobina cis-diamindihloridoplatina(II)kompleksa, poznatijeg pod imenom cisplatina (cis-DDP) i sličnih kompleksa platine povećalo je interesovanje za dobijanje još efikasnijih kompleksa drugih metala i liganada. Među prvim kompleksima korišćenim u kliničkim ispitivanjima protiv tumora bili su paladijum(II) analozi cisplatine. Iako prvobitni rezultati nisu bili ohrabrujući, kompleksi paladijuma(II) su mnogo šire proučavani. Paladijum(II) kompleksi su skoro uvek pokazivali manju antitumorsku aktivnost u odnosu na odgovarajuće komplekse platine zbog njihove velike labilnosti. Da bi se ovi problemi prevazišli, mnoga istraživanja su bila usmerena ka upotrebi helatnih liganada koji bi umanjili reaktivnost paladijum(II) kompleksa.The discovery of anticancer activity of cis-diammindichloridoplatinum(II)complexes, better known as cisplatin (cis-DDP) and related platinum complexes has stimuled the interest for obtaining more efficient complexes of other metals and ligands. Some the first complexes used in clinical treatments against tumors were palladium(II)complexes as analogues of cisplatin. Although the first results were not encouraging,palladium complexes have been studied to longer extent. Palladium(II) complexes show less antitumor activity than corresponding platinum complexes due to their high instability. In order to overcome these problems, many studies have been directed toward the use of chelating ligands which would reduce the reactivity of palladium(II) complexes

Breast Infiltrating Ductal Carcinoma: Analysis of Hormone, HER-2 Receptors and Ki-67 Proliferation Marker

The aim of this study was to analyse breast carcinomas with discordant receptor status, probably hormonal dependent (estrogen receptor (ER) positive, progesterone receptor (PR) negative or ER-PR+ subgroup profile) infiltrating ductal breast carcinomas not otherwise specified (IDC NOS). Specimens from 90 IDC NOS were grouped into three categories according to hormonal status: dependent (D) (ER+PR+), probably dependent (PD) (ER+PR- or ER-PR+) and non-dependent (ND) (ER-PR-); they were evaluated considering some established prognostic parameters in breast carcinomas. Statistically significant difference was found between tumor receptor status distribution and menopausal status (p= 0.0235), age of the patients (p=0.000467), histological grade (p=0.000003), vascular invasion (p=0.006), HER-2 status (p=0.0039) and Ki-67 proliferation rate (p=0.000311). D tumors were found exclusively in post-menopausal patients (average age 68.9 years), most of which had intermediate (II) grade, without vascular invasion, with HER-2 status score predominantly 0 or 1+ and lower Ki-67 proliferation rate. PD tumors were found predominantly in younger post-menopausal patients (average age 57.5 years), with vascular invasion found in 23% of the cases. ND tumors mostly had higher histological grade, showed the highest percentage of the Ki-67 positive tumor cells and vascular invasion in 30% of the cases. We conclude that the patients with PD breast carcinomas were younger post-menopausal women with the tumors moderately differentiated, HER-2 score 0 or 1+ and with lower Ki-67 proliferation rate

Analysis of stay-cable vibrations at the Franjo Tuđman Bridge in Dubrovnik

Na postojećim ovješenim mostovima najčešće su uočene vibracije kosih vješaljki uzrokovane istovremenim djelovanjem kiše i vjetra. Vibracije kosih vješaljki mogu se procijeniti usporedbom s ovješenim mostovima u sličnim uvjetima i analitičkim postupcima, a najtočnije procjene dobivaju se ispitivanjima u zračnom tunelu. Pojava tih vibracija može se spriječiti aerodinamičkim, konstrukcijskim i mehaničkim mjerama. U radu je prikazana teorijska podloga i analiza vibracija kosih vješaljki na Mostu Franja Tuđmana u Dubrovniku.Stay cable vibrations occurring on existing cable stayed bridges are most often due to simultaneous rain and wind action. Although stay cable vibrations can be estimated by comparison to cable stayedbridges under similar conditions and by analytical procedures,, most accurate estimates can be obtained by wind tunnel testing. Stay cable vibrations can be prevented by aerodynamic, structural and mechanical measures. The theoretical base and the analysis of stay cable vibrations on the Franjo Tuđman Bridge in Dubrovnik are presented in the paper

Pelješac bridge

U radu je prikazan i detaljno opisan projekt mosta Pelješac. Mostom preko morskog tjesnaca između Kleka i poluotoka Pelješca, duljine oko 2400 m uspostavit će se čvrsta veza između dijelova hrvatskog teritorija, u svrhu povezivanja i razvitka Dubrovnika i cijele Hrvatske najjužnije županije. Ovaj je most svojim dimenzijama i značajem daleko najveći i najsloženiji graditeljski projekt u Hrvatskoj i jedan od najvećih u Europi. Detaljno je opisan ovaj složeni graditeljski pothvat.The design of the Pelješac Bridget is presented and described indetail in the paper. The bridge over the sea strait between Klek and the Pelješac Peninsula, about 2400 m in length, will provide a fixed road link between distinct parts of the Croatian territory, with the purpose of establishing proper connections and fostering development in Dubrovnik and in the entire southernmost county of Croatia. By its size and significance, this bridge is by far the largest and most complex construction project in Croatia, and one of the largest in Europe. This complex construction project is described in full detail

New overpasses on Croatian motorways

U članku se prikazuju rezultati studije izrađene na Građevinskom fakultetu u Zagrebu koju su naručile Hrvatske autoceste. Cilj je studije bio razviti nove tipove nadvožnjaka na autocestama koji će biti funkcionalni, sigurni za korisnike autoceste i estetski dobro oblikovani. Rezultati studije su tri nova, originalna tipa nadvožnjaka uz razradu mnogo detalja i varijantnih rješenja za primjenu koji će oplemeniti nove autoceste i unaprijediti jedan segment našeg građevinarstva.Results of the study comissioned by Hrvatske autoceste and prepared at the Faculty of Civil Engineering, Zagreb, are presented. The objective of the study was to develop new types of motorway overpasses that will be functional, safe for motorway users, and aesthetically pleasing. The study resulted in the definition of three new and original overpass types, with many details and practical alternatives that are sure to give new dignity to future motorways, and hence improve this segment of our civil engineering practice

Design of novel thiourea derivatives of naproxen with potential antitumor activity

In the search for potent biologically active molecules, thiourea and other structure-related derivatives such as thiosemicarbazones have attracted great attention. In the past two decades, thiourea derivatives have been recognized as promising class of anticancer drugs due to their inhibitory activity against various targets, such as protein kinases and topoisomerases [1,2]. In this work, molecular docking analyses were performed on 20 thiourea derivatives of naproxen, previously designed by our group, in order to find their potential mechanisms of action. Designed derivatives contain amino acids and aromatic amines in the side chains. Following 3D structures of selected protein kinases involved in multidrug resistance were taken from PDB: 1M17 (EGFR), 3E87 (AKT2), 3HNG (VEGFR1) and 4JSV (mTOR). The receptor sites were prepared using MAKE Receptor 3.2.0.2 software [3]. Ligands were prepared in OMEGA 2.5.1.4 [4,5] and multiconformational binary files were generated. The FRED 3.2.0.2 software [6-8] was used for the analysis of binding poses into the receptor sites. The key binding interactions were observed for derivatives 1 (with AKT2 and mTor) and 20 (with EGFR and VEGFR1). Therefore, these derivatives possess the best multitarget potential and represent potential candidates for targeting multidrug resistant tumors (Figure 1)

In silico estimation of COX-2 and 5-LOX inhibitory potential of some novel thiourea derivatives of naproxen

Design of dual COX-2/5-LOX inhibitors can be considered an adequate approach in the development of new anti-inflammatory drugs with less pronounced side effects. The aim of the present research was to examine the binding potential of the seven newly designed thiourea derivatives of naproxen towards COX-2 and 5-LOX. The binding analysis of ligand conformations was performed by OEDocking 3.2.0.2 software. The binding potential assessment revealed that thiourea derivatives of naproxen exhibited a comparable binding affinity as naproxen towards COX-2. The highest number of key binding interactions with 5-LOX was formed by compound 5, whereas compound 6 established the most stable complex (-9.29 kcal/mol). According to the obtained results, derivatives 5 and 6 can be considered as dual COX-2/5-LOX inhibitors with potential anti-inflammatory activity. However, none of the investigated compounds were able to form three hydrogen bonds with the binding site of COX-2, as well as three key hydrogen bonds with the active site of 5-LOX