PMID: 11900865Mar 20, 2002Paper

Reactions of purines-containing butenolides with L-cysteine or N-acetyl-L-cysteine as model biological nucleophiles: a potent mechanism-based inhibitor of ribonucleotide reductase caused apoptosis in breast carcinoma MCF7 cells

European Journal of Medicinal Chemistry
Gholam Hossein HakimelahiS Hakimelahi

Abstract

Thiols are the most reactive nucleophilic reagents among the biological models investigated. The reactivity of butenolides 1a-c, 2-4, and 6-8 toward L-cysteine, a model biological nucleophile, was studied spectrophotometrically. The rates of the reactions were measured and correlated with antitumour activity of these molecules. N-Acetylcysteine addition product 5, resulting from the treatment of butenolide 4 with glutathione precursor, N-acetyl-L-cysteine, was isolated. Unlike purine-containing gamma-(Z)-ethylidene-2,3-dimethoxybutenolides 1a-c, 4, 6, and 7, adduct 5 and butenolides 10-12 did not exhibit inhibitory activity against murine leukemias (L1210 and P388), breast carcinoma (MCF7), and human T-lymphoblasts (Molt4/C8 and CEM/0) cell lines. As such, the biological activity of purine-containing butenolides can be attributed to their adenine moiety as a recognition site as well as their reactivity towards the cysteine residues of functional proteins forming covalent bond via reverse Michael type addition. Adenine-containing phosphonothioanhydride derivative 8 was also synthesised. Its reaction with N-acetyl-L-cysteine produced N,S-diacetylcysteine and thiophosphonate 9. Compound 9 did not exhibit anticancer activity; yet i...Continue Reading

References

Jul 1, 1985·Journal of Bacteriology·M Russel, P Model
Aug 14, 1973·Biochemistry·G N Sando, P C Hogenkamp
Dec 1, 1971·Journal of Medicinal Chemistry·S M KupchanA M Thomas
Mar 1, 1970·Analytical Biochemistry·J R Steeper, C D Steuart
Jan 1, 1983·Annual Review of Biochemistry·A Meister, M E Anderson
Oct 1, 1993·Journal of Toxicology and Environmental Health·D L SpringerC G Edmonds
Jul 20, 1999·Journal of Medicinal Chemistry·S Raić-MalićM Mintas
Feb 7, 2001·The Journal of Biological Chemistry·S HakimelahiM Pasdar
Jun 22, 2000·Journal of Cellular Biochemistry·V UmanskyA Ushmorov
May 18, 2001·Journal of Medicinal Chemistry·G H HakimelahiY S Wen

❮ Previous
Next ❯

Citations

Apr 10, 2007·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Yi-Mei WangHai-Ying Yang
Oct 1, 2013·Neuroscience Letters·A N Lozano-OndouaT W Vanderah
Feb 23, 2019·Organic & Biomolecular Chemistry·Mengchen YangShurong Ban
Mar 15, 2010·Molecular Informatics·Aliuska M HelgueraM Natália D S Cordeiro
Jul 31, 2019·Antioxidants·Andrijana Meščić MacanSilvana Raić-Malić
Sep 26, 2009·Toxicology Mechanisms and Methods·Yi-Mei WangShuang-Qing Peng
Mar 8, 2007·Journal of Medicinal Chemistry·Aliuska Morales HelgueraM Natália D S Cordeiro

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis