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

Abstract

The a-hydroxyphosphonate generated from dialkyl phosphites and 1-phenyl-1H-pyrazole-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 K 2 CO 3 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, SK-OV-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 IC 50 values ranging from 16.6 to 26.9 and 17.2 to 36.9 lmol L À1 , respectively (for 5-fluorouracil IC 50 : 17.7 to 38.8 lmol L À1 ). Phosphorylmethyl methylcarbamothioate, in particular was more potent than 5-fluorouracil against all tested human carcinoma cell lines. ª 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Promiscuous Lipase-Catalyzed Markovnikov Addition of H-Phosphites to Vinyl Esters for the Synthesis of Cytotoxic α-Acyloxy Phosphonate Derivatives

“…α-Hydroxy phosphonates are recognized as a valuable class of substances exhibiting interesting medicinal and agricultural properties [ 1 , 2 , 3 , 4 ]. α-Hydroxy phosphonate derivatives are of great importance due to their various biological actions and therapeutic applications such as bactericidal [ 5 ], fungicidal [ 6 ], antitumor [ 7 ], and HIV inhibitory activities [ 8 ]. The high interest in this class of compounds has been reflected in numerous publications on their synthesis, modification, and application not only in medical chemistry [ 9 , 10 , 11 , 12 , 13 , 14 ].…”

Microwave-assisted synthesis of novel sulfonamide-based compounds bearing α-aminophosphonate and their antimicrobial properties

“…In line with the foregoing considerations and as part of our pre-vious and on-going studies [48][49][50][51][52], we have designed a new se-ries of αaminophosphonates tagged with sulfisoxazole via MWI-assisted Kabachnik-Fields reaction. The synthesized compounds were thereafter tested in vitro for their antimicrobial activities (Fig.…”

Efficient Approaches for the Synthesis of Substituted Thiazolo[3,2‐a]‐benzimidazole‐Phosphonates and ‐Phosphinic Diamide Derivatives

“…Furthermore, synthesis and applications of di-and monophosphonoantes as well as phosphonoamidate-substituted heterocycles are also known by our scientific work. [21][22][23][24][25][26][27] In a series of papers, Abdel-Aziz et al reported the synthesis and reactions of thiazolo[3,2-a]benzimidazoles with different nucleophiles. [28][29][30] In this investigation, we studied the reactions of E-3-(dimethylamino)-1-(3-methylbenzo[d]thiazolo[3,2-a]imidazol-2-yl)prop-2-en-1-one (1) and 1-(3-methylbenzo[d] thiazolo[3,2-a]imidazol-2-yl)ethanone (12) with trialkyl phosphites 2ac, dialkylphosphonates 6a-c, and tris(dialkylamino)phosphines 8a,b as well as the constitution of the products.…”