3D-QSAR, synthesis, and antimicrobial activity of 1-alkylpyridinium compounds as potential agents to improve food safety.

Cetylpyridinium chloride (CPC), an alkylpyridinium compound has been recently approved by the US Food and Drug Administration to reduce bacterial contamination in poultry. Although CPC is very effective and has a very good safety record, its relatively high lipophilicity may limit its use in high fat containing foods such as beef. In this study we present the CoMFA analysis (3D-QSAR) of the antimicrobial activity of 60 N-alkylpyridinium compounds against different bacteria. CoMFA contours showed that the activity is highly influenced by the steric factor. Based in these contours we designed new candidates, which were synthesized and characterized by spectroscopic data. MIC activity over Gram positive and Gram negative microorganisms validated the 3D-QSAR study.

Synthesis and comparative molecular field analysis (CoMFA) of argentatin B derivatives as growth inhibitors of human cancer cell lines.

Synthesis, characterization, anticancer activity, and comparative molecular field analysis (CoMFA) of 14 argentatin B (1) analogs are described. The effect of argentatin B derivatives on the growth of K562 (leukemia), PC-3 (prostate), U251 (CNS), and HCT-15 (colon) human cancer cell lines was determined using the sulforhodamine B test. The most active compound in this series, 2-formyl-(16beta,24R)-16,24-epoxy-25-hydroxycycloart-1-en-3-one (12), was about 35-50 times more potent than argentatin B (1). Structures were built using the X-ray crystallography of six derivatives for 3D modeling with Sybyl6.9. CoMFA of Log (1/IC50) in K562 cell line gave q2 = 0.507, r2 = 0.907, and three components. The standard deviation CoMFA contours indicate that increased activity is associated with a bulky group at C-2, a C1-C2 double bond, and low electronic density at C-25. Experimental Log P values for argentatin B and one derivative were 1-2 Log units more hydrophilic than the calculated CLog P values.