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In this study, we have synthesized a series of dinuclear and trinuclear gold(III) complexes of the general formula [Au2(N–N)Cl6] (1–3) for dinuclear and [Au3(N–N)2Cl8]+ (4–6) for trinuclear compounds, respectively, in which N–N is a bidentate ligand (1,4-diaminobutane; 1,6-diaminohexane or 1,8-diaminooctane). These complexes were characterized by elemental analysis, molar conductivity, and spectroscopic techniques (IR, UV–Vis, 1H NMR, ESI–MS). We performed DFT calculations to get insight into the geometry of the studies complexes. DNA-binding studies were performed by UV–Vis spectrophotometry and fluorescence spectroscopy. The results of competitive reactions between gold(III) complexes and ethidium bromide (EB) towards DNA have shown that selected complexes can displace EB from DNA-EB adduct. In addition, these experiments confirm that polynuclear gold(III) complexes interact with DNA covalently or via intercalation. Furthermore, high values of binding constants of gold(III) complexes towards bovine serum albumin (BSA) protein indicate good binding affinity. In addition, redox stability of complexes in the presence of DNA/BSA was confirmed by cyclic voltammetry. Results of the interactions between gold(III) complexes with DNA/BSA were discussed in reference to molecular docking data obtain by Molegro virtual docker. The cytotoxic activity of synthesized gold(III) complexes was evaluated on human breast cancer cell line (MDA-MB-231), human colorectal cancer cell line (HCT-116), and normal human lung fibroblast cell line (MRC-5). All complexes dose-dependently reduced cancer and normal cells viabilities, with significant cytotoxic effects (IC50 < 25 μM) for trinuclear gold(III) complexes (4, 5) on HCT-116 cells. Graphic abstract: [Figure not available: see fulltext.].

Interactions of copper(II) complexes which contain S-alkyl derivatives of thiosalicylic acid (alkyl = methyl, ethyl, propyl and butyl; aryl = benzyl), marked as 1–5, with guanosine-5′-monophosphate (5′-GMP) and calf thymus DNA (CT-DNA) were studied. Kinetics of substitution reactions of 1–5 with 5′-GMP and CT-DNA were investigated under pseudo-first-order conditions at 310 K and pH = 7.2 in 25 mM Hepes buffer using stopped-flow method. All complexes have high affinity toward studied bio-molecules. Additionally, interactions with CT-DNA were followed by absorption spectroscopy and fluorescence quenching measurements. The results indicate that complexes bind to DNA exhibiting high binding constants (Kb = 104 M−1). During the examination of competitive reactions with ethidium bromide (EB), results showed that complexes can replace EB-bound DNA. In addition, a new crystal structure of the binuclear Cu(II) complex with S-substituted thiosalicylate derivative has been reported. In the present series of Cu(II) complexes the crystal structure is the first example of a complex comprising an S-aryl derivative of thiosalicylate ligand. Through comparative study of structural properties of six molecules from four crystal structures we examined the structural variations, potentially important for biological activity of these complexes. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

Phospholipids are the main components of biological membranes. This book covers the production, properties and use of natural and synthetic phospholipids as drug delivery systems for therapeutic agents, including small drugs, peptides/proteins and nucleic acids. Also covered in this book are major recent findings that elucidate the biochemical features of polyphenol-phospholipid interactions and their influence on the mechanical and biochemical properties of membranes; research on the metabolism of phospholipids and their fatty acids content, fragmentally altered in various diseases; information dealing with the various aspects of different metallodrugs with phospholipids and their analysis in the light of their importance in cancer therapy; the synthesis and metabolism of major membrane phospholipids; and an in-depth discussion on the synthesis of other phopholipids, including lecithin are examined as well.

Otkrićem antitumorskog dejstva cisplatine od strane B. Rozenberga 60-ih godina dvadesetog veka otpočela je prava revolucija u terapiji teških bolesti lekovima na bazi kompleksa jona prelaznih metala. Mnogobrojna istraživanja u ovoj oblasti dovela su do toga da se danas pored cisplatine i neki drugi kompleksi Pt(II), kao što su karboplatina i oksaliplatina, intezivno koriste u hemoterapiji. Poslednjih 40 godina veliki broj drugih kompleksa platine sintetisan je sa ciljem da se postigne bolja aktivnost u odnosu na cisplatinu. Pored kompleksa Pt(II) sa uobičajenom kvadratno-planarnom strukturom ispitivani su i tzv. neklasični kompleksi platine, gde spadaju kompleksi Pt(IV), polinuklearni Pt(II) kompleksi, ali i kompleksi drugih jona metala. Kompleksi Ru imaju veliki potencijal za upotrebu u terapiji kancera zbog svojih značajnih karakteristika, kao što su kinetika ligandne izmene, širok opseg oksidacionih stanja i sličnih osobina rutenijuma i gvožđe u biohemijskim procesima. Kinetika ligandne izmene određuje biološku aktivnost kompleksa metala i njegovu interakciju sa makromolekulima, kao što su proteini. Takođe su podjednako važne i interakcije sa amino kiselinama, peptidima i nukleotidima. Parametri kinetike ligandne izmene za komplekse Ru(II) i Ru(III) jona su slični parametrima za komplekse Pt(II) jona. Rutenijum u fiziološkim uslovima postoji u tri oksidaciona stanja: Ru(II), Ru(III) i Ru(IV), koja karakterišu različite biološke aktivnosti. Kompleksi Ru(III) su biološki inertniji od analognih Ru(II) i Ru(IV) kompleksa, a posebno je važno to što pod uticajem sredine mogu promeniti svoje oksidaciono stanje. Rutenijum se na molekularnom nivou ponaša kao gvožđe i može se vezati za albumin i transferin. Pošto ćelije kancera imaju povećanu potrebu za gvožđem, na njihovoj površini je povećan broj transferinskih receptora od 2 do 12 puta u odnosu na zdrave ćelije. Kompleksi Ru se tada vezuju za transferin i time selektivnije deluju na tumorska tkiva, pa su i sporedni neže, Discovery of the antitumor activity of cisplatin by B. Rosenberg during the 60’s of the twentieth century started a real revolution in the treatment of severe disease drugs based on the transition metal ion complexes. Most of the results in this field have led to the conclusion that today, beside cisplatin, other complexes of Pt(II), such as carboplatin and oxaliplatin, are used extensively in chemotherapy. In the past 40 years a large number of other platinum complexes were synthesized in order to obtain a compound with better activity than cisplatin. In addition, the complexes of Pt(II) with conventional square-planar structure and so-called nonclassical platinum complexes, which include complexes of Pt(IV) and polynuclear Pt(II) complexes have been studied as well. However, the complexes of other metal ions were also included in these investigations. Ruthenium complexes have a great potential for application in cancer therapy because of their significant features, such as kinetics of ligand exchange, different oxidation states and property that ruthenium can mimic iron in biochemical processes. Kinetics of the ligand exchange determines their biological activity and interactions with macromolecules, such as proteins. The interactions with other biomolecules (amino acids, peptides and nucleotides) are also very important. The parameters of the ligand exchange kinetics for the Ru(II) and Ru(III) complexes are very similar to the values obtained for Pt(II) complexes. Under the physiological conditions ruthenium can exist in three oxidation states: Ru(II), Ru(III) and Ru(IV). Each of them has different biological acivity. Complexes of Ru(III) are biologically more inert than analogue Ru(II) or Ru(IV) complexes. Nevertheless, the ruthenium ion can easily change its oxidation state depending of the environment. Ruthenium can mimic iron and it may be bound to albumin and transferrin. Since cancer cells have an increased need for iron, on their surface accumulates increa

The present study was conducted in order to evaluate efficiency of a personal body cooling system based on passive evaporative technologies and its effects on test subjects and their psycho-physiological suitability during exertional heat stress in hot environment. Performed results are based on conducted tests in climatic chamber in the Military Medical Academy Institute of Hygiene in Belgrade. Ten male test subjects were subjected to exertional heat stress test consisted of walking on motorized treadmill at a speed of 5 km/h in hot environment. Tests were performed with and without cooling system. As a physiological strain indicator the following parameters have been determined: mean skin temperature, tympanic temperature, heart rate and sweat rate. Results confirmed that cooling vest worn over the clothes was able to attenuate the physiological strain levels during exercise, when compared to identical exposure without the cooling system., Rad predstavlja rezultate naučnih istraživanja na polju efikasnosti sistema za hlađenje tela iz grupe pasivnih sistema na bazi isparavanja i njegov uticaj na fiziološku podobnost ljudi u uslovima izloženosti fizičkom naporu i ekstremno visokim temperaturama. Podaci i dobijeni rezultati zasnovani su na ispitivanjima sprovedenim u klimatskoj komori Instituta za higijenu VMA u Beogradu. Deset ispitanika muškog pola dobrovoljno je podvrgnuto testovima toplotnog opterećenja usled fizičkog napora, izazvanog hodanjem na pokretnoj traci sa brzinom hoda od 5 km/h, u toploj sredini (temperatura vazduha 40 °C). Testovi su realizovani sa ispitanicima srednjih godina (27.2±2.6), sličnih antropometrijskih parametara (74±7 kg, 184±9 cm), u varijanti nošenja radne odeće bez ikakvog rashladnog sistema (opcija NoCOOL) i uz upotrebu rashladnih prsluka za hlađenje tela, model Arctic Heat® (opcija ACOOL). Kao pokazatelji fiziološkog opterećenja određivane su: srednja temperatura kože (Tsk), timpanična temperatura (Tty) i frekvencija srčanog rada (HR), dok je intenzitet znojenja (SwR) izračunat kao pokazatelj vodeno-elektrolitskog statusa. U svim slučajevima izlaganje fizičkom naporu u toploj sredini indukovalo je fiziološki odgovor, manifestovan kroz povećanje timpanične temperature, frekvencije srčanog rada i intenziteta znojenja. U varijantama primene rashladnog prsluka (COOL), timpanična temperatura i srednja temperatura kože su imale značajno niže vrednosti (p lt 0,05), kao i intenzitet znojenja (p lt 0,001). Eksperimentalni rezultati dokazali su uticaj rashladnog prsluka, korišćenog preko radne odeće, na snižavanje nivoa fiziološkog opterećenja tokom izlaganja korisnika ekstremnim uslovima, u poređenju sa identičnim testovima u varijanti bez hlađenja tela.

This works describes synthesis, characterization and potential cytotoxity of O,O'- -dialkyl-(S,S)-ethylenediamine-N,N'-di-2-(4-methyl)-pentanoic acid, [(S,S)-H4eddl]Cl2, as well as their corresponding palladium(II), platinum(II) and platinum(IV) complexes. Esters (S,S)-R2eddl·2HCl (R = ethyl, n-propyl, n-butyl and n-pentyl) were obtained by instillation of thionyl chloride in an appropriate absolute alcohol, and then refluxing with addition of (S,S)-ethylenediamine-N,N'-di-2-(4-methyl)-pentanoic acid. All of the esters were obtained as dihydrochlorides: (S,S)-Et2eddl·2HCl, (S,S)-Pr2eddl·2HCl, (S,S)-Bu2eddl·2HCl, (S,S)-Pe2eddl·2HCl. Esters were characterized by elemental analysis, IR and NMR spectroscopy, and in the case of (S,S)-Pr2eddl·2HCl the structure was confirmed by X-ray structural analysis.