Selective cytotoxicity

British investigators (Haddow and Timmis 1951) synthesized and studied esters of the methanesulfonic acid. The most active derivative was the dimethylsulfonic ester of 1,4-butanedione, known as busulfan. Busulfan interacts with the thiol groups of proteins and amino acids some of its metabolites can alkylate the thiols of cysteine, peptides and proteins. Busulfan exerts selective cytotoxic activity in hematopoietic bone marrow cells and inhibits the formation of granulocytes and platelets. It slightly affects the lymphoid tissue. 

Proteasomal inhibition represents a novel strategy in cancer treatment and the small molecule Bortezomid (PS-341, Velcade ) has been approved for the treatment of refractory and relapsed multiple myeloma, a proliferative disease of plasma cells. Bortezomid inhibits an active site in a proteasome subunit and remarkably shows selective cytotoxicity to cancer cells. Although the underlying mechanisms are not completely understood bortezomid apparently induces a cell stress response in these tumor cells followed by caspase-dependent apoptosis. Whether bortezomid is beneficial for the treatment of other proliferative disease is currently being tested in clinical trials. 

Seinen W, Penninks AH (1979) Immune suppression as a consequence of a selective cytotoxic activity of certain organometallic compounds on thymus and thymus-dependent... 

Bfx Fx 126 Hypoxic selective cytotoxicity compound 126 DNA-interaction was studied showing poor affinity for this biomolecule [219-222]... 

Pepper C, Mahdi JG, Buggins AG et al (2011) Two novel aspirin analogues show selective cytotoxicity in primary chronic lymphocytic leukaemia cells that is associated with dual inhibition of Rel A and COX-2. Cell Prolif 44 380-390... 

FU to enter the cell, and may trap intracellular nucleoside metabolites, hence increasing cytotoxicity (24,25), but the exact mechanism underlying the selective cytotoxicity against tumor cells compared with normal tissues still needs to be determined. 

They concluded that the parasiticidal action of trioxanes involved reductive cleavage of the peroxide bond by intracellular iron-sulphur redox centres (rather than heme) and subsequent alkylation of the redox centre. This type of redox centre is known to exist in many enzymes and Wu and coworkers proposed that structural differences between those in the parasite and those in mammalian systems could account for the high selective cytotoxicity of artemisinin. 

Salomon, A.R. Zhang, Y. Khosla, C. (2001) Structure-activity relationships within a family of selectively cytotoxic maaolide natural products. Org. Lett., 3, 57-9. 

Betulinic acid (50) Selective cytotoxic activity against melanoma cell lines1 [46]... 

Stirpe, F, Wawrzynczak, E. J., Brown, A. N. F, Knyba, R E., Watson, G. J., Barbieri, L., and Thorpe, P. E. (1988) Selective cytotoxic activity of nrununo-toxins composed of a monoclonal anti-Thyl 1 antibody and the ribosome-inacti-vating proteins bryodin and momordin. Br J Cancer 58, 558-561. 

Mycophenolate mofetil is a functionally selective cytotoxic agent for B and T lymphocytes, where it blocks the production of guanosine nucleotides required for DNA synthesis. For purine biosynthesis, B and T lymphocytes rely on de novo synthesis rather than on the salvage pathway. Lymphocytes have little or no salvage pathway as opposed to other blood marrow elements and parenchymal cells that... 

Luo, Y. and G. D. Prestwich. 1999. Synthesis and selective cytotoxicity of a hyaluronic acid-antitumor bioconjugateBioconjugate Cheml0 755-763. 

Endo, N. et al. (1987) Target-selective cytotoxicity of methotrexate conjugated with monoclonal anti-MM46 antibody, Cancer Immunol. Immunother. 25, 1-6. 

R. Rodriguez, E. R. Schuur, H. Y. Lim, G. A. Henderson, J. W. Simons, and D. R. Henderson, Prostate attenuated replication competent adenovirus (ARCA) CN706 a selective cytotoxic for prostate-specific antigen-positive prostate cancer cells, Cancer Res. 57 2559 (1997). 

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