Synthesis, characterization, in vitro SAR study, and preliminary in vivo toxicity evaluation of naphthylmethyl substituted bis-imidazolium salts.

A series of novel bis-imidazolium salts was synthesized, characterized, and evaluated in vitro against a panel of non-small cell lung cancer (NSCLC) cells. Two imidazolium cores were connected with alkyl chains of varying lengths to develop a structure activity relationship (SAR). Increasing the length of the connecting alkyl chain was shown to correlate to an increase in the anti-proliferative activity.

A novel in vitro metric predicts in vivo efficacy of inhaled silver-based antimicrobials in a murine Pseudomonas aeruginosa pneumonia model.

To address the escalating problem of antimicrobial resistance and the dwindling antimicrobial pipeline, we have developed a library of novel aerosolizable silver-based antimicrobials, particularly for the treatment of pulmonary infections. To rapidly screen this library and identify promising candidates, we have devised a novel in vitro metric, named the "drug efficacy metric" (DEM), which integrates both the antibacterial activity and the on-target, host cell cytotoxicity. DEMs calculated using an on-target human bronchial epithelial cell-line correlates well (R > 0.

Synthesis, characterization, in vitro SAR and in vivo evaluation of N,N'bisnaphthylmethyl 2-alkyl substituted imidazolium salts against NSCLC.

Alkyl- and N,N'-bisnaphthyl-substituted imidazolium salts were tested in vitro for their anti-cancer activity against four non-small cell lung cancer cell lines (NCI-H460, NCI-H1975, HCC827, A549). All compounds had potent anticancer activity with 2 having IC values in the nanomolar range for three of the four cell lines, a 17-fold increase in activity against NCI-H1975 cells when compared to cisplatin. Compounds 1-4 also showed high anti-cancer activity against nine NSCLC cell lines in the NCI-60 human tumor cell line screen.

Synthesis, characterization, and in vitro SAR evaluation of N,N'-bis(arylmethyl)-C-alkyl substituted imidazolium salts.

A series of C-alkyl substituted N,N'-bis(arylmethyl)imidazolium salts were synthesized, characterized, and tested for their in vitro anti-cancer activity against multiple non-small cell lung cancer cell lines by our group and the National Cancer Institute's-60 human tumor cell line screen to establish a structure-activity relationship. Compounds are related to previously published N,N'-bis(arylmethyl)imidazolium salts but utilize the historical quinoline motif and anion effects to increase the aqueous solubility. Multiple derivatives displayed high anti-cancer activity with IC values in the nanomolar to low micromolar range against a panel of non-small cell lung cancer cell lines.

Synthesis, anti-proliferative activity, SAR study, and preliminary in vivo toxicity study of substituted N,N'-bis(arylmethyl)benzimidazolium salts against a panel of non-small cell lung cancer cell lines.

A series of N,N'-bis(arylmethyl)benzimidazolium salts have been synthesized and evaluated for their in vitro anti-cancer activity against select non-small cell lung cancer cell lines to create a structure activity relationship profile. The results indicate that hydrophobic substituents on the salts increase the overall anti-proliferative activity. Our data confirms that naphthylmethyl substituents at the nitrogen atoms (N(N)) and highly lipophilic substituents at the carbon atoms (C and C(C)) can generate benzimidazolium salts with anti-proliferative activity that is comparable to that of cisplatin.

Anti-tumor activity of lipophilic imidazolium salts on select NSCLC cell lines.

The anti-tumor activity of imidazolium salts is highly dependent upon the substituents on the nitrogen atoms of the imidazolium cation. We have synthesized and characterized a series of naphthalene-substituted imidazolium salts and tested them against a variety of non-smallcell lung cancer cell lines. Several of these complexes displayed anticancer activity comparable to cisplatin.

Imidazolium salts as small-molecule urinary bladder exfoliants in a murine model.

We present a novel family of small-molecule urinary bladder exfoliants that are expected to be of great value in preclinical studies of urologic conditions and have improved potential for translation compared with prior agents. There is broad urologic interest in the therapeutic potential of such exfoliating agents. The primary agent used in preclinical models, the cationic peptide protamine sulfate (PS), has limited translational potential due to concerns including systemic adverse reactions and bladder tissue injury.

Crystal structure of 9-methacryloylanthracene.

In the title compound, C18H14O, with systematic name 1-(anthracen-9-yl)-2-methyl-prop-2-en-1-one, the ketonic C atom lies 0.2030 (16) Å out of the anthryl-ring-system plane. The dihedral angle between the planes of the anthryl and methacryloyl moieties is 88.

Preparation and in vitro antimicrobial activity of silver-bearing degradable polymeric nanoparticles of polyphosphoester-block-poly(L-lactide).

The development of well-defined polymeric nanoparticles (NPs) as delivery carriers for antimicrobials targeting human infectious diseases requires rational design of the polymer template, an efficient synthetic approach, and fundamental understanding of the developed NPs, e.g., drug loading/release, particle stability, and other characteristics.

Mathematical modelling of Pseudomonas aeruginosa biofilm growth and treatment in the cystic fibrosis lung.

Lung failure due to chronic bacterial infection is the leading cause of death for patients with cystic fibrosis (CF). It is thought that the chronic nature of these infections is, in part, due to the increased tolerance and recalcitrant behaviour of bacteria growing as biofilms. Inhalation of silver carbene complex (SCC) antimicrobial, either encased in polymeric biodegradable particles or in aqueous form, has been proposed as a treatment.

Synthesis, characterization, and antimicrobial activity of silver carbene complexes derived from 4,5,6,7-tetrachlorobenzimidazole against antibiotic resistant bacteria.

Silver N-heterocyclic carbene complexes have been shown to have great potential as antimicrobial agents, affecting a wide spectrum of both Gram-positive and Gram-negative bacteria. A new series of three silver carbene complexes (SCCs) based on 4,5,6,7-tetrachlorobenzimidazole has been synthesized, characterized, and tested against a panel of clinical strains of bacteria. The imidazolium salts and their precursors were characterized by elemental analysis, mass spectrometry, (1)H and (13)C NMR spectroscopy, and single crystal X-ray diffraction.

Nanoparticle encapsulated silver carbene complexes and their antimicrobial and anticancer properties: a perspective.

This perspective discusses the uses of silver for both antimicrobial and anticancer applications. It focuses on the synthesis of silver N-heterocyclic carbene complexes (SCCs) and their in vitro efficacy against a broad spectrum of bacteria, as well as their antitumor properties. Finally, different polymeric nanoparticles are discussed as delivery vehicles for the encapsulation of SCCs and other therapeutic agents for use in vivo.