To determine the cytotoxicity of chlorambucil and one of its nitro-derivatives, conjugated to prasterone and pregnenolone, towards eight human cancer cell-lines.
Four ester prodrugs derived from the bifunctional alkylating agent chlorambucil, and one of its nitro-derivatives, 3-nitrochlorambucil conjugated to prasterone and pregnenolone, were synthesized and tested for their cytotoxic activity against eight human cell lines, using the standard MTT assay. A comparison between the esters and the controls, namely chlorambucil and 3-nitrochlorambucil would suggest that all four esters possess to varying degrees, specificity towards the breast adenocarcinoma cell line (MDA-mb468) than the other seven cells' lines tested. The overall findings are encouraging since it infers that these lipophilic esters not only have the ability to traverse specific cell membranes but also exhibit cytotoxicity towards most of the cell lines tested.
Shervington
Leroy A
LA
School of Pharmacy and Pharmaceutical Sciences, University of Central Lancashire, Preston, UK. lashervington@uclan.ac.uk
Smith
Nigel
N
Norman
Emma
E
Ward
Timothy
T
Phillips
Roger
R
Shervington
Amal
A
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002699:Chlorambucil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003687:Dehydroepiandrosterone / Q000737:chemistry*; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D009369:Neoplasms / Q000473:pathology; D009574:Nitro Compounds / Q000737:chemistry*; D011284:Pregnenolone / Q000737:chemistry*
D000970:Antineoplastic Agents; D004952:Esters; D009574:Nitro Compounds; D002699:Chlorambucil; D003687:Dehydroepiandrosterone; D011284:Pregnenolone