In this study, the antibacterial, cytotoxic and antiproliferative activities of novel thiosemicarbazide derivatives were assessed. Our results demonstrated that some of the novel compounds possess good antibacterial properties against Staphylococcus epidermidis, Streptococcus mutans and Streptococcussanguinis and are only slightly cytotoxic; thus, they exhibit an excellent therapeutic index, which is higher than that of ethacridine lactate. Moreover, our data showed that compounds 2 and 4 have an antiproliferative activity against human breast adenocarcinoma and human hepatocellular carcinoma cell lines. We expect that the novel thiosemicarbazide derivatives can be used as agents for treatment of dental caries and also for chemotherapy support.Electronic supplementary materialThe online version of this article (doi:10.1007/s00044-016-1599-6) contains supplementary material, which is available to authorized users.

High-performance liquid chromatography (HPLC), over-pressured-layer chromatography (OPLC) and thin-layer chromatography (TLC) techniques with micellar mobile phases were proposed to evaluate the lipophilicity of 21 newly synthesized 1,2,4-triazoles, compounds of potential importance in medicine or agriculture as fungicides. Micellar parameters log k m were compared with extrapolated R M 0 values determined from reversed-phase (RP) TLC experimental data obtained on RP-8 stationary phases as well as with log P values (Alog Ps , AClog P , Alog P , Mlog P , KowWin, xlog P 2 and xlog P 3) calculated from molecular structures of solutes tested. The results obtained by applying principal component analysis (PCA) and linear regression showed considerable similarity between partition and retention parameters as alternative lipophilicity descriptors, and indicated micellar chromatography as a suitable technique to study lipophilic properties of organic substances. In micellar HPLC, RP-8e column (Purospher) was applied, whereas in OPLC and TLC, RP-CN plates were applied, which was the novelty of this study and allowed the use of micellar effluents in planar chromatography measurements.

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Infectious diseases are one of the most important and urgent health problems in the world. According to the World Health Organization (WHO) statistics, infectious and parasitic diseases are a cause of about 16% of all deaths worldwide and over 40% of deaths in Africa. A considerable progress that has been made during last hundred years in the fight against infectious diseases, in particular bacterial infections, can be attributed mainly to three factors: (1) the general improvement of living conditions, in particular sanitation; (2) development of vaccines and (3) development of efficient antibacterial drugs. Although considerable progress in reduction of the number of cases of bacterial infections, especially in lethal cases, has been made, continued cases and outbreaks of these diseases persist, which is caused by different contributing factors. Indeed, during last sixty years antibacterial drugs were used against various infectious diseases caused by bacterial pathogens with an undoubtable success. The most fruitful period for antibiotic development lasted from 40's to 60's of the last century and resulted in the majority of antibiotics currently on the market, which were obtained by screening actinomycetes derived from soil. Although the market for antibacterial drugs is nowadays greater than 25 billion US dollars per year, novel antibacterial drugs are still demanded due to developed resistance of many pathogenic bacteria against current antibiotics. In the last five years, one can observe a dramatic increase in cases of resistant bacteria strains (e.g. Klebsiella pneumoniae and E. coli) which are responsible for difficult to treat pneumonia and infections of urinary tract. The development of resistant bacteria strains is a side effect of antibiotic application for treatment: the infections become untreatable as a result of the existence of antibiotic-tolerant persisters. In this review, we discuss the challenges in antibacterial drug discovery, including the molecular basis of drug resistance, drug targets for novel antibacterial drugs, and new compounds (since year 2010) from different chemical classes with antibacterial activity, focusing on structure-activity relationships.

A series of 1,2,4-triazole derivatives were synthesized and assigned as potential anti-tuberculosis substances. The molecular and crystal structures for the model compounds C1, C12, and C13 were determined using X-ray analysis. The X-ray investigation confirmed the synthesis pathway and the assumed molecular structures for analyzed 1,2,4-triazol-5-thione derivatives. The conformational preferences resulting from rotational degrees of freedom of the 1,2,4-triazole ring substituents were characterized. The lipophilicity (logP) and electronic parameters as the energy of frontier orbitals, dipole moments, NBO net charge distribution on the atoms, and electrostatic potential distribution for all structures were calculated at AM1 and DFT/B3LYP/6-311++G(d,p) level. The in vitro test was done against M. tuberculosis H37Ra, M. phlei, M. smegmatis, and M. timereck. The obtained results clearly confirmed the antituberculosis potential of compound C4, which turned out to be the most active against Mycobacterium H37Ra (MIC = 0.976 μg/mL), Mycobaterium pheli (MIC = 7.81 μg/mL) and Mycobacerium timereck (62.6 μg/mL). Satisfactory results were obtained with compounds C8, C11, C14 versus Myc. H37Ra, Myc. pheli, Myc. timereck (MIC = 31.25−62.5 μg/mL). The molecular docking studies were carried out for all investigated compounds using the Mycobacterium tuberculosis cytochrome P450 CYP121 enzyme as molecular a target connected with antimycobacterial activity.

: The information about the presence of free radicals in biological materials was given for the first time about 70 years ago. Since then, numerous scientific studies have been conducted and the science of free radicals was born. Today we know that free radicals are by-products of enzymatic reactions occurring in the organism. They are produced during endogenous processes such as: cell respiration, phagocytosis, biosynthesis, catalysis, and biotransformation. They can also be produced by exogenous processes (radiation, sunlight, heavy metals, bacteria, fungi, protozoa and viruses). The overproduction of free radicals affects the aging processes, oxidative stress (OS) and takes part in the pathogenesis of various diseases. Among them are cancer, rheumatoid arthritis, neurodegenerative diseases: Alzheimer and Parkinson, pulmonary diseases, atherosclerosis and DNA damage. Compounds with antioxidant activity are very important nowadays because they allow organisms to keep a balance between the production of free radicals and the speed of their neutralization in the body. Next to the natural antioxidants (flavonoids, carotenoids, vitamins, etc.), synthetic ones are also of great importance. Among synthetic compounds with antioxidant activity are 1,2,4-triazoles and its derivatives. 1,2,4-Triazoles are heterocyclic compounds with three nitrogen atoms. Due to a broad spectrum of biological activities, these derivatives have been of interest to scientists for many years. Some of them are also used as drugs. The finding of new synthetic compounds with antioxidant features in the triazole group has become important problem of medicinal chemistry.

The condensation of endo-S-methyl-N 0 -(bicyclo[2.2.1]hept-5-ene-2,3-dicarbonyl) isothiosemicarbazide with 12 primary amines was investigated. The molecular structure of all new products (3a-3l) was confirmed by spectroscopic methods, including 1D/2D NMR, IR spectroscopy and mass spectrometry, and an X-ray crystallography of three selected representative amide crystals. The 2,3-disubstitution of norbornene (endo-bicyclo[2.2.1]hept-5-ene) unit stabilizes overall cisoid orientation of substituents. Spectroscopic and structural analyses indicate that for the series of 12 derivatives the rigid molecular part is endo-bicyclo[2.2.1]hept-5-ene-2-carboxamide fragment. The specific orientation of the 3-(methylthio)-1H-1,2, 4-triazole unit, second substituent to the norbornene skeleton, is correlated with the chemical character of N-amide substituents. Phenyl derivatives stabilize transoid orientation of the N-H triazole and C=O amide bonds, whereas the alkyl (methylene or methine) spacer promotes cisoid orientation of these bonds and provides possibility for an intramolecular hydrogen bonding. The solid-state IR spectra and X-ray analysis indicate three patterns of intermolecular association in this series of crystals. Hydrogen bonds observed in crystals influence positions of vibrational bands corresponding to m NH (3322-3180 cm -1 ), m C=O (1634-1676 cm -1 ), and d NH (1600-1500 cm -1 ).