Ten phenolic compounds were isolated from a butanol fraction of sage extracts. Their structures determined by spectral methods (NMR, MS, IR). Among them, novel compound, 4-hydroxyacetophenone-4-O-β-d-apiofuranosyl-(1→6)-O-β-d-glucopyranoside, was identified. Two test systems, DPPH free radical scavenging activity and cation ABTS•+ activity, used to evaluate their antioxidant activity. The most active found be rosmarinic acid luteolin-7-O-β-glucopyranoside. Keywords: Sage; Salvia officinalis;...

Several 2'-aryl-5-substituted-2,5'-bi-1H-benzimidazole derivatives were synthesized and evaluated as topoisomerase I poisons for their cytotoxicity toward the human lymphoblast cell line RPMI 8402. This study focused on 18 2,5'-bi-1H-benzimidazole which contained either a 5-cyano, 5-(aminocarbonyl), or 5-(4-methylpiperazinyl) group. Among these bibenzimidazoles, pharmacological activity of 2'-phenyl influence different positional isomers 2'-tolyl group 2'-naphthyl moiety inhibitory determined.

The clinical development of FtsZ-targeting benzamide compounds like PC190723 has been limited by poor drug-like and pharmacokinetic properties. Development prodrugs (e.g., TXY541) resulted in enhanced pharmaceutical properties, which, turn, led to improved intravenous efficacy as well the first demonstration oral vivo against both methicillin-sensitive Staphylococcus aureus (MSSA) methicillin-resistant S. (MRSA). Despite being efficacious vivo, TXY541 still suffered from suboptimal...

The breakage/reunion reaction of DNA topoisomerase II (TOP2) can be interrupted by intercalators (e.g., doxorubicin), enzyme binders etoposide), or lesions abasic sites) to produce TOP2-mediated damage. Here, we demonstrate that thiol alkylation TOP2 also This conclusion is supported the following observations using purified TOP2: (1) Thiol-reactive quinones were shown induce cleavage. (2) compounds such as N-ethylmaleimide (NEM), disulfiram, and organic disulfides [e.g.,...

Seasonal and pandemic influenza viruses continue to be a leading global health concern. Emerging resistance the current drugs variable efficacy of vaccines underscore need for developing new flu that will broadly effective against wild-type drug-resistant strains. Here, we report discovery development class inhibitors targeting cap-snatching endonuclease activity viral polymerase. A high-resolution crystal form 2009 H1N1 polymerase acidic protein N-terminal domain (PAN) was engineered used...

Spectroscopic, calorimetric, DNA cleavage, electrophoretic, and computer modeling techniques have been employed to characterize the binding topoisomerase poisoning properties of three protoberberine analogs, 8-desmethylcoralyne (DMC), 5,6-dihydro-8-desmethylcoralyne (DHDMC), palmatine, which differ in chemical structures their B- and/or D-rings. topoisomerase-mediated cleavage assays revealed that these compounds were unable poison mammalian type II topoisomerase. By contrast, analogs...

5H-8,9-Dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxydibenzo[c,h][1,6]naphthyridin-6-one (ARC-111) has potent TOP1-targeting activity and pronounced antitumor activity. Several analogues of ARC-111 were synthesized with NH2, N-alkyl, N,N-dialkyl, pyrrolidinyl, piperidinyl, piperazinyl substituents at the 2-position 5-ethyl group. The relative cytotoxicity these structural assessed in RPMI8402 P388 tumor cells their camptothecin-resistant variants CPT-K5 P388/CPT45, respectively....

A high-performance liquid chromatography coupled with electrospray ionization mass spectrometry (LC/ESI-MS) method under selected ion monitoring mode (SIM) was developed to quantitate the predominant catechins, catechin, epicatechin, epicatechin-3-O-gallate, and epigallocatechin-3-O-gallate, in medicinal plant catechu (Acacia catechu). Other major secondary products including caffeine, flavanol dimers, flavonol glycosides were also identified by their molecular peaks fragmentation using...

The synthesis of a series 24-membered pyridine-containing polyoxazole macrocycles is described. Seventeen new were evaluated for cytotoxic activity against RPMI 8402, KB-3, and KB-3 cell lines that overexpress the efflux transporters MDR1 (KBV-1) BCRP (KBH5.0). Macrocycles in which pyridyl-polyoxazole moiety linked by 1,3-bis(aminomethyl)phenyl group with 5-(2-aminoethyl)- (18) or 5-(2-dimethylaminoethyl)- substituent (19) displayed greatest potency. These compounds exhibit exquisite...

In the effort to combat antibiotic resistance, inhibitors of essential bacterial protein FtsZ have emerged as a promising new class compounds with clinical potential. One such inhibitor (TXA707) is associated potent activity against isolates methicillin-resistant Staphylococcus aureus (MRSA) that are resistant current standard-of-care antibiotics. However, mutations in S. (SaFtsZ) confer resistance TXA707 been observed, Gly196 and Gly193 residues being among most prevalent. Here, we describe...

Seasonal and pandemic influenza outbreaks remain a major human health problem. Inhibition of the endonuclease activity RNA-dependent RNA polymerase is attractive for development new agents treatment infection. Our earlier studies identified series 5- 6-phenyl substituted 3-hydroxypyridin-2(1H)-ones that were effective inhibitors endonuclease. These as bimetal chelating ligands binding to active site enzyme. In present study, several aza analogues these phenyl 3-hydroxypyridin-2(1H)-one...

An investigation of Salvia officinalis L. has led to the isolation three new phenolic glycosides, 6-O-caffeoyl-beta-D-fructofuranosyl-(2-->1)-alpha-D-glucopyranosid e (1), 1-O-caffeoyl-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyrano side (2), and 1-O-p-hydroxybenzoyl-beta-D-apiofuranosyl-(1-->6)-beta-D-glucop yranos ide (3). Elucidation structures 1-3 was based on interpretation FABMS 1D 2D NMR spectra. Compounds 1 2 were found be moderately active as antioxidants in DPPH test metmyoglobin test.

Protoberberines represent a structural class of organic cations that induce topoisomerase I-mediated DNA cleavage, behavior termed I poisoning. We have employed broad range biophysical, biochemical, and computer modeling techniques to characterize cross-correlate the DNA-binding poisoning properties four protoberberine analogues differ with respect substituents on their A- and/or D-rings. Our data reveal following significant features: (i) The binding protoberberines unwinds duplex by...

Oxazole-containing macrocycles represent a promising class of anticancer agents that target G-quadruplex DNA. We report the results spectroscopic studies aimed at defining mode, energetics and specificity with which hexaoxazole-containing macrocycle (HXDV) binds to intramolecular quadruplex formed by human telomeric DNA model oligonucleotide d(T2AG3)4 in presence potassium ions. HXDV solely nucleic acid form, but not duplex or triplex form. stoichiometry two drug molecules per quadruplex,...