One-pot three-component synthesis of peptidomimics for investigation of antibacterial and antineoplastic properties

The alpha-hydroxyphosphonate generated from dialkyl phosphites and 1-phenyl-1-Hpyrazole-4-carbaldehyde derivative was, in situ, trapped by isothiocyanates, isocyanates or acetic anhydride to produce dialkyl phosphorylmethyl-carbamothioates, -carbamates and/or -methyl acetates in good yields. The reactions were carried out in tetrahydrofuran (THF) in one step at room temperature, using K2CO3 catalyst. Antimicrobial and antineoplastic activities of the synthesized compounds were estimated. The results showed that all new compounds cause moderate to good antibiotic activities. However, phosphorylmethylcarbamothioates exhibited the highest growth inhibition. Furthermore, selected nine new synthesized compounds were evaluated for anticancer activity against eight human tumor cell lines (MCF7, MDA-MB-435, BT-549, IGROVI, SKOV-3, PX-3, PU-145, and HEPG2). The majority of these compounds revealed moderate to potent activity against MCF7, PU-145, and HEPG2. Among them, two of the phosphorylmethylcarbamo thioates showed excellent broad spectrum of anticancer activity with IC50 values ranging from 16.6 to 26.9 and 17.2 to 36.9 lmol L-1, respectively (for 5-fluorouracil IC50: 17.7 to 38.8 lmol L-1). Phosphorylmethyl methylcarbamothioate, in particular was more potent than 5-fluorouracil against all tested human carcinoma cell lines. (C) 2015 The Authors. Production and hosting by Elsevier B. V. on behalf of King Saud University.