Kemijski sastav endemske biljke Centaurea austro-anatolica i ispitivanje antimikrobnog djelovanja protiv multi-rezistentnih bakterija

Hexane, chloroform, ethyl acetate and ethanolic extracts of the aerial parts of C. austro-anatolica Hub.-Mor. (Asteraceae) were evaluated against microorganisms, including multi-resistant bacteria, using a paper disc diffusion method. The chloroform extract exhibited significant antibacterial activity toward all bacteria tested. The chemical composition of the chloroform extract was determined by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The major compounds of the extract were caryophyllene oxide (21.32 %), spathulenol (10.86 %), n-tricosanol (9.58 %) and geranyl isovalerate (8.71 %).Heksanski, kloroformski, etil-acetatni i etanolni ekstrakti vršnih dijelova biljke C. austro-anatolica Hub.-Mor. (Asteraceae) ispitivani su na antimikrobno djelovanje protiv multi-rezistentnih bakterija, koristeći difuzijsku metodu na papirnom disku. Kloroformski ekstrakt pokazao je značajno antibakterijsko djelovanje protiv svih testiranih bakterija. Kemijski sastav tog ekstrakta određivan je plinskom kromatografijom (GC) i plinskom kromatografijom-spektrometrijom masa (GC-MS). Najvažniji sastojci ekstrakta bili su kariofilen oksid (21,32 %), spatulenol (10,86 %), n-trikozanol (9,58 %) i geranil izovalerat (8,71 %)

Simple chalcones and bis -chalcones ethers as possible pleiotropic agents

The synthesis, the antioxidative properties and the lipoxygenase (LOX) and acetylcholinesterase (AChE) inhibition of a number of 4-hydroxy-chalcones diversely substituted as well as of a series of bis-chalcones ether derivatives are reported. The chalcones derivatives were readily produced using a Claisen-Schmidt condensation in a ultra sound bath in good yields. The structures of the synthesized compounds were confirmed by spectral and elemental analysis. Their lipophilicity is experimentally determined by reversed-phase thin-layer chromatography method. Most of them are potent in vitro inhibitors of lipid peroxidation and of LOX. Compounds b2 and b3 were found to be the most potent LOX and AChE inhibitors among the tested derivatives with a significant anti-lipid peroxidation profile. The results led us to propose these enone derivatives as new multifunctional compounds against Alzheimer's disease. The results are discussed in terms of structural and physicochemical characteristics of the compounds. Moreover, the pharmacokinetic profile of these compounds was investigated using computational methods. © 2015 Informa UK Ltd

Bioactive sesquiterpene lactones from Centaurea species and their cytotoxic/cytostatic activity against human cell lines in vitro

Sesquiterpene lactones isolated from the aerial parts of various species of the genus Centaurea were examined for their in vitro cytotoxic/cytostatic activity against five human cell lines (i.e., DLD1, SF268, MCF7, H460 and OVCAR3). Compounds 1-4 were isolated from C. zuccariniana, 5 and 6 from C. achaia, 7 from C. thessala ssp. drakiensis and compounds 8 and 9 from C. deusta. Compound 1, 8α-O-(3,4-dihydroxy-2-methylenebutanoyloxy)-dehydromelitensine was found to be the most active, exhibited a considerable growth inhibiting activity against three of the cell lines tested, while compound 5 8α-O-(3-hydroxy-2-methylenepropanoyl)dehydromelitensin exhibited a growth inhibiting effect against most of the tested cell lines. A new eudesmanolide (8α-hydroxysonchucarpolide, 4) was isolated from C. zuccariniana and its structure was elucidated by spectroscopic methods

Structure-activity relations on [1-(3,5-difluoro-4-hydroxyphenyl)-1H- pyrrol-3-yl]phenylmethanone. the effect of methoxy substitution on aldose reductase inhibitory activity and selectivity

Based on our previous work, we studied the effect of methoxy-substitution as well as the regioposition of the benzoyl-moiety of 4a [(1-(3,5-difluoro-4- hydroxyphenyl)-1H-pyrrol-3-yl)(phenyl)methanone]. On this basis, compounds 4b-c and 5a-c were synthesized and assayed for aldose and aldehyde reductase inhibitory activity. Furthermore, a 4,6-difluoro-5-hydroxyphenyl pattern (9) was studied, in order to verify the optimum position of the phenol-moiety. Compound 5b emerged as the most potent and selective inhibitor. Moreover, further assays proved 5b as a potent antioxidant and an inhibitor of sorbitol accumulation in isolated rat lenses. Combining the above attributes, 5b could serve as a lead compound targeted at long-term diabetes complications. © 2011 Elsevier Ltd. All rights reserved

The effect of an estrone D-lactam steroid ester derivative on breast cancer cells and its predicted binding interactions with the ligand binding domain of estrogen receptor-α

In order to further improve the toxicity profile and the anticancer effect of chlorambucil (CBL), we have synthesized a new estrone D-lactam steroidal ester of CBL (ESBL). The aim of this study was to investigate the in vitro activity of ESBL against primary breast carcinoma (BC) cells of operable tumors in comparison with CBL. Cells derived from fresh tumor sections that were obtained from 28 postmenopausal women with ductal BC were treated with CBL and ESBL. Apoptotic cells were distinguished from viable ones with flow cytometric methods. ESBL generated a significantly higher rate of cell apoptosis and cytotoxicity than CBL. ESBL cytotoxic effect demonstrated a significant positive weak to moderate dose-dependent correlation with the ER expression. ESBL produced antineoplastic activity superior to CBL on primary BC tumors in vitro. Moreover, a docking study on the binding interactions of ESBL with the ligand binding domain (LBD) of estrogen receptor-α (ERα) was investigated. ESBL was found to be positioned inside the binding cavity with its steroidal moiety, whereas the alkylating moiety protruded out of receptor's pocket. Copyright © 2006 Cognizant Comm. Corp

Biological and computational evaluation of resveratrol inhibitors against Alzheimer’s disease

It has been reported that beta amyloid induces production of radical oxygen species and oxidative stress in neuronal cells, which in turn upregulates b-secretase (BACE-1) expression and beta amyloid levels, thereby propagating oxidative stress and increasing neuronal injury. A series of resveratrol derivatives, known to be inhibitors of oxidative stress-induced neuronal cell death (oxytosis) were biologically evaluated against BACE-1 using homogeneous timeresolved fluorescence (TRF) assay. Correlation between oxytosis inhibitory and BACE-1 inhibitory activity of resveratrol derivatives was statistically significant, supporting the notion that BACE-1 may act as pivotal mediator of neuronal cell oxytosis. Four of the biologically evaluated resveratrol analogs demonstrated considerably higher activity than resveratrol in either assay. The discovery of some ‘‘hits’’ led us to initiate detailed docking studies associated with Molecular Dynamics in order to provide a plausible explanation for the experimental results and understand their molecular basis of action

Rational design, efficient syntheses and biological evaluation of N,N’-symmetrically bis-substituted butylimidazole analogs as a new class of potent Angiotensin II receptor blockers

A series of symmetrically bis-substituted imidazole analogs bearing at the N-1 and N-3 two biphenyl moieties ortho substituted either with tetrazole or carboxylate functional groups was designed based on docking studies and utilizing for the first time an extra hydrophobic binding cleft of AT1 receptor. The synthesized analogs were evaluated for their in vitro antagonistic activities (pA2 values) and binding affinities (elogIC50 values) to the Angiotensin II AT1 receptor. Among them, the potassium (elogIC50 ¼ 9.04) and the sodium (elogIC50 ¼ 8.54) salts of 4-butyl-N,N0 -bis{[20 -(2H-tetrazol-5-yl)biphenyl-4-yl]methyl} imidazolium bromide (12a and 12b, respectively) as well as its free acid 11 (elogIC50 ¼ 9.46) and the 4- butyl-2-hydroxymethyl-N,N0 -bis{[20 -(2H-tetrazol-5-yl)biphenyl-4-yl]methyl}imidazolium bromide (14) (elogIC50 ¼ 8.37, pA2 ¼ 8.58) showed high binding affinity to the AT1 receptor and high antagonistic activity (potency). The potency was similar or even superior to that of Losartan (elogIC50 ¼ 8.25, pA2 ¼ 8.25). On the contrary, 2-butyl-N,N0 -bis{[20 -[2H-tetrazol-5-yl)]biphenyl-4-yl]methyl}imidazolium bromide (27) (elogIC50 ¼ 5.77) and 2-butyl-4-chloro-5-hydroxymethyl-N,N0 -bis{[20 -[2H-tetrazol-5-yl)]biphenyl-4-yl] methyl}imidazolium bromide (30) (elogIC50 ¼ 6.38) displayed very low binding affinity indicating that the orientation of the n-butyl group is of primary importance. Docking studies of the representative highly active 12b clearly showed that this molecule has an extra hydrophobic binding feature compared to prototype drug Losartan and it fits to the extra hydrophobic cavity. These results may contribute to the discovery and development of a new class of biologically active molecules through bis-alkylation of the imidazole ring by a convenient and cost effective synthetic strateg