Hetero-Multivalent Targeted Liposomal Drug Delivery to Treat Infections.

is the leading nosocomial and community-acquired pathogen causing a plethora of acute and chronic infections. The Centers for Disease Control and Prevention has designated multidrug-resistant isolates of as a serious threat. A novel delivery vehicle capable of specifically targeting  , and encapsulating antimicrobials, may address the challenges associated with these infections.

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.

N-Acetyl cysteine abrogates silver-induced reactive oxygen species in human cells without altering silver-based antimicrobial activity.

Silver-based antimicrobials are widely used topically to treat infections associated with multi-drug resistant (MDR) pathogens. Expanding this topical use to aerosols to treat lung infections requires understanding and preventing silver toxicity in the respiratory tract. A key mechanism resulting in silver-induced toxicity is the production of reactive oxygen species (ROS).

Synthesis, characterization, and biological activity of a triphenylphosphonium-containing imidazolium salt against select bladder cancer cell lines.

Imidazolium salts have shown great promise as anticancer materials. A new imidazolium salt (TPP1), with a triphenylphosphonium substituent, has been synthesized and evaluated for in vitro and in vivo cytotoxicity against bladder cancer. TPP1 was determined to have a GI ranging from 200 to 250 μM over a period of 1 h and the ability to effectively inhibit bladder cancer.

Recent Developments in the Medicinal Applications of Silver-NHC Complexes and Imidazolium Salts.

Because of their great structural diversity and multitude of chemical properties, N-heterocyclic carbenes (NHCs) have been utilized in a variety of capacities. Most recently, NHCs have been utilized as carrier molecules for many transition metals in medicinal chemistry. Specifically, Ag(I)-NHCs have been investigated as potent antibacterial agents and chemotherapeutics and have shown great efficacy in both in vitro and in vivo studies.

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, 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.