1,3,5-Triazine Nitrogen Mustards with Different Peptide Group as Innovative Candidates for AChE and BACE1 Inhibitors

A series of new analogs of nitrogen mustards (4a–4h) containing the 1,3,5-triazine ring substituted with dipeptide residue were synthesized and evaluated for the inhibition of both acetylcholinesterase (AChE) and β-secretase (BACE1) enzymes. The AChE inhibitory activity studies were carried out using Ellman’s colorimetric method, and the BACE1 inhibitory activity studies were carried out using fluorescence resonance energy transfer (FRET). All compounds displayed considerable AChE and BACE1 inhibition. The most active against both AChE and BACE1 enzymes were compounds A and 4a, with an inhibitory concentration of AChE IC50 = 0.051 µM; 0.055 µM and BACE1 IC50 = 9.00 µM; 11.09 µM, respectively.

Development of a method for derivatization of ethanolamines and its application to sand samples

Nitrogen mustards are dangerous and available blistering chemical warfare agents. In the presented study, six derivatization methods are compared for the analysis of degradation products of the most important blistering nitrogen mustards (ethyl diethanolamine, methyl diethanolamine and triethanolamine) by gas chromatography coupled with mass spectrometry. Five silylation methods (using BSTFA and BSA) and one trifluoroacetylation method (using TFAA) were tested. The derivatization reactions were performed in acetonitrile. As the method with optimal results, trifluoroacetylation by TFAA was selected. Analytes reacted with the corresponding reagent rapidly, quantitatively, with stable kinetics and at room temperature. Calibration curves for quantitative analysis of ethanolamines after TFAA derivatization were created. Correspond-ing detection limits varied between 9?10-3 and 7?10-5 mmol?dm-3 for the tested analytes. The developed method was applied for the analysis of ethanolamines after extraction from sand using acetonitrile. Limits of detection were 11.4 to 12.3 ?g of the analyte in 1 g of sand. It is encouraged to use the developed method in military deployable laboratories designated for rapid identification of chemical warfare agents and corresponding degradation products.

Discovery of steroidal lactam conjugates of POPAM-NH2 with potent anticancer activity

Aim: Steroidal prodrugs of nitrogen mustards such as estramustine and prednimustine have proven effective anticancer agents in clinical use since the 1970s. In this work, we aimed to develop steroidal prodrugs of the novel nitrogen mustard POPAM-NH2. POPAM-NH2 is a melphalan analogue that was coupled with three different steroidal lactams. Methodology: The new conjugates were preclinically tested for anticancer activity against nine human and one rodent cancer experimental models, in vitro and in vivo. Results & conclusion: All the steroidal alkylators showed high antitumor activity, in vitro and in vivo, in the experimental systems tested. Moreover, these hybrid compounds showed by far superior anticancer activity compared with the alkylating agents, melphalan and POPAM-NH2.