Cytotoxic activity of new racemic and optically active N-phosphonoalkyl bicyclic β-amino acids against human malignant cell lines

• Published in: Amino acids 2012-10, Vol.43 (4), p.1445-1450
• Main Authors: Todorov, Petar T., Wesselinova, Diana W., Pavlov, Nikola D., Martinez, Jean, Calmes, Monique, Naydenova, Emilia D.
• Format: Article
• Language: English
• Subjects: Amino acids; Amino Acids - chemical synthesis; Amino Acids - pharmacology; Analytical Chemistry; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Antiproliferatives; Biochemical Engineering; Biochemistry; Biomedical and Life Sciences; Bridged Bicyclo Compounds - chemical synthesis; Bridged Bicyclo Compounds - pharmacology; Cell Line, Tumor; Cell Survival - drug effects; Constraints; Derivatives; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Human; Humans; Inhibitory Concentration 50; Life Sciences; Neurobiology; Optical activity; Organophosphonates - chemical synthesis; Organophosphonates - pharmacology; Original Article; Proteomics; Stereoisomerism; Toxicology; Tumors
• ISSN: 0939-4451; 1438-2199
• DOI: 10.1007/s00726-012-1217-y

The cytotoxic effects of novel racemic and optically active constrained N -phosphonoalkyl bicyclic β -amino acids were tested against a panel of human tumor cell lines. All of the compounds investigated exhibited different concentration-dependent antiproliferative effects against the HT-29, MDA-MB-231, HepG2 and HeLa cell lines after 24 h treatment. The most sensitive cells were the HeLa cells at various concentrations of the four compounds tested. The aminophosphonate 3 exerted the most pronounced antiproliferative effect against the HeLa cells (inhibition of the cell vitality up to 70% at 0.5 mg/ml) and was not toxic to the normal Lep3 cells at lower concentration. Furthermore, the N -phosphonophenyl derivatives 1 and 2 displayed antiproliferative effect against mainly the MDA-MB-231 tumour cells at higher concentration.