Novel lavendamycin analogues with various substituents were synthesized and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor agents. Pictet-Spengler condensation of quinoline- or quninoline-5,8-dione aldehydes with tryptamine or tryptophans yielded the lavendamycins. Metabolism studies with recombinant human NQO1 revealed that addition of NH2 and CH2OH groups at the quinolinedione-7-position and indolopyridine-2'-position had the greatest positive impact on substrate specificity. The best and poorest substrates were 37 (2'-CH2OH-7-NH2 derivative) and 31 (2'-CONH2-7-NHCOC3H7-n derivative) with reduction rates of 263 +/- 30 and 0.1 +/- 0.1 micromol/min/mg NQO1, respectively. Cytotoxicity toward human colon adenocarcinoma cells was determined for the lavendamycins. The best substrates for NQO1 were also the most selectively toxic to the NQO1-rich BE-NQ cells compared to NQO1-deficient BE-WT cells with 37 as the most selective. Molecular docking supported a model in which the best substrates were capable of efficient hydrogen-bonding interactions with key residues of the active site along with hydride ion reception.

Superparamagnetic iron oxide nanoparticles (SPION) have been widely used in medicine for magnetic resonance imaging, hyperthermia, and drug delivery applications. The effect of SPION on animal cells has been a controversial issue on which there are many contradictions. This study focused on preparation of SPION with novel biocompatible coatings, their characterization, and cytotoxicity evaluation. An amino acid (glycine) and two novel lipo-amino acids (2 amino-hexanoic acid and 2 amino-hexadecanoic acid) coated magnetic nanoparticles were characterized by various physicochemical means such as X-ray diffraction (XRD), transmission electron microscopy (TEM), vibrating sample magnetometry (VSM), differential scanning calorimetry (DSC), and infrared spectroscopy (FT-IR). The cytotoxicity profile of the synthesized nanoparticles on Hep-G2 cells as measured by MTT assay showed the nanoparticles are nontoxic and the cell growth is promoted by SPION. Moreover, lipoamino acid coating SPION appear more beneficial than the other ones. By increasing concentration of SPION, growth enhancing impact will attenuate and toxicity will appear. Although the aggregation of SPION can affect the results, the gradual delivery of ferric/ferrous ions into cells is the main cause of this growth promotion effect. Conclusively, this study shows that lipoamino acid coating SPION can be used for various biomedical purposes.

A variety of alcohols were acetylated in good to excellent yields with acetic anhydride in the presence of a catalytic N-bromosuccinimide (NBS) in CH 2 Cl 2 and at room temperature. The reactions are clean and almost in all cases no detectable byproduct were observed.