Synthesis, spectroscopic characterization, stability assessment and DNA-binding of new 2,6-piperidinedione derivatives

• Published in: Farmaco (Società chimica italiana : 1989) 2001-10, Vol.56 (10), p.763-770
• Main Authors: Abou-Zeid, Laila, El-Mowafy, Abdalla M, El-Kerdawy, Mohammed M, Hamza, Huda, Abdel-Hamid, Mohammed E
• Format: Article
• Language: English
• Subjects: 2,6-Piperidinediones; Antineoplastic agents; Biological and medical sciences; Chromatography, High Pressure Liquid; DNA - drug effects; DNA-binding; Drug Stability; General aspects; HPLC; Magnetic Resonance Spectroscopy; Medical sciences; MS/MS; NIR; Pharmacology. Drug treatments; Piperidones - chemical synthesis; Piperidones - chemistry; Piperidones - metabolism; Structure-Activity Relationship
• ISSN: 0014-827X; 1879-0569
• DOI: 10.1016/S0014-827X(01)01131-4

This work reports on structural characterization of new antineoplaston (ANP) representatives, namely 3-(benzoylamino)-2,6-piperidinedione (BPD), 3-(4-methoxybenzoylamino)-2,6-piperidinedione (MPD) and 3-( p-nitrobenzoylamino)-2,6-piperidinedione (NPD). These compounds were prepared by reacting N-(4-substituted benzoyl)-glutamines with N-hydroxysuccinimide to afford the corresponding esters, which were heated to produce the corresponding 2,6-piperidinedione (PD) compounds. Non-destructive analytical procedures such as 1H NMR and NIR analyses confirmed the postulated chemical structures of these PD compounds. HPLC chromatograms at an ambient temperature or from solutions preheated at 30, 40 or 60 °C displayed only a single peak for each compound. Combination of heat with pH modification had virtually no effect on the obtained peaks, thus attesting to the stability and purity of these compounds. MS analysis displayed molecular mass ions indicative of BPD, MPD and NPD at m/ z 233.4, 263.2 and 278.3, respectively. The fragmentation patterns using MS/MS analyses conformed to the structural and molecular formulae of the prepared compounds. Furthermore, preliminary biological assessments showed the capacity of these compounds to bind to the DNA. NPD, but not BMP or MPD, had a superior affinity to the DNA than the prototype ANP-A10.