N-Functionalization of β-aminophosphonates: cytotoxic effects of the new derivatives

• Published in: Organic & biomolecular chemistry Vol. 22; no. 19; pp. 3940 - 3950
• Main Authors: Keglevich, Gyorgy, Varga, Petra Regina, Dinnyesi, Emoke, Szalai, Zsuzsanna, Bosze, Szilvia, Rita, Olahne Szabo, Drahos, Laszlo, Karaghiosoff, Konstantin
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 15.05.2024; Royal Society of Chemistry
• Subjects: Acylation; Amines; Amines - chemical synthesis; Amines - chemistry; Amines - pharmacology; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Chemistry; Chemistry, Organic; Chlorides; Cytotoxicity; Drug Screening Assays, Antitumor; Humans; Inorganic salts; Low temperature; Molecular Structure; NMR; Nuclear magnetic resonance; Organophosphonates - chemical synthesis; Organophosphonates - chemistry; Organophosphonates - pharmacology; Phosphine; Phosphine oxide; Physical Sciences; Science & Technology; Structure-Activity Relationship; Tumor cell lines
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/d4ob00243a

beta-Aminophosphonates obtained by the Michael addition of primary amines to the double bond of diethyl vinylphosphonate proved to be suitable starting materials (amine components) in the Kabachnik-Fields reaction with formaldehyde and dialkyl phosphites or secondary phosphine oxides to afford N-phosphonylmethyl- and N-phosphinoylmethyl-beta-aminophosphonates. On the other hand, the starting aminophosphonates were modified by N-acylation using acid chlorides. The N-acyl products were found to exist in a dynamic equilibrium of two conformers as suggested by the broad NMR signals. At 26 degrees C, there may be rotation around the N-C axis of the acylamide function. At the same time, low-temperature NMR measurements at -5 degrees C revealed the presence of two distinct rotamers that could be characterized by P-31, C-13 and H-1 NMR data. The modified beta-aminophosphonic derivatives were subjected to a comparative structure-activity analysis on MDA-MB-231, PC-3, A431 and Ebc-1 tumor cell lines, and in a few cases, significant activity was detected.