To determine the cytotoxicity of chlorambucil and one of its nitro-derivatives, conjugated to prasterone and pregnenolone, towards eight human cancer cell-lines

Abstract

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.

Synthesis and Evaluation of New Potential Benzo[a]phenoxazinium Photosensitizers for Anticancer Photodynamic Therapy

“…Other compounds are new synthetic benzo[ a ]phenoxazinium derivatives: PS2 possesses a morpholinoethylamine moiety, which is a well-known ligand for targeting lysosome [ 21 ]; PS3 is equipped with a biotin moiety, which is a well-known tumor-targeting molecule [ 22 ] and has been used for selective delivery of PS to cancer tissues [ 23 , 24 ]; PS4 was a conjugate of benzo[ a ]phenoxazinium and pregnenolone. Pregnenolone, known as a precursor to most hormones, had been explored as carrier of anticancer drugs [ 25 ]. In addition, several types of pregnenolone derivatives were reported to have anticancer activity by our and other groups [ 26 , 27 , 28 ].…”

Design and synthesis of 21-alkynylaryl pregnenolone derivatives and evaluation of their anticancer activity

“…Thus, the nitrochlorambucil ester of pregnenolone exhibited a significant in vitro cytotoxic activity in brain posterior fossa, medulloblastoma (Daoy), and lung large cell carcinoma (H460) cell lines. 6 In addition, pregnenolone derivatives bearing heterocyclic moieties were found to exhibit anticancer activity. More specifically, 17-pyrazolinyl derivatives of pregnenolone possess interesting activity in vitro against a panel of five human cancer cell lines and especially against HT-29, HCT-15 and 502713 cell lines.…”

A Review on Azole Derivatives as Potent Anticancer Agents

“…Within the next few decades, it is expected that figure of yearly deaths due to cancer will raise from 14 million in 2014 to 22 million 4 . Drugs that are presently existing for the treatment of cancer embrace bio-alkylating agents 5,6 , antimetabolic agents (fluorouracil) 7,8 , antibiotics as anticancer 9 ,besides complexes from plants and their derivatives 10 . Though, appropriate dosages of anticancer medications to eradicate tumor cells are often lethal to normal tissues, consequently prominent to numerous side effects, which confines the treatment efficiency.…”

“…The palladium complexes are slightly affected by the nature of the anion and the inhibitory activity was found to be in decreasing order as follows: Cl (1) ¼ Br (2) > SCN (4) > I (3) > NO3 (5). It was found that the PdeL (1) complex possesses a moderate antitumor activity and is more toxic than the platinum complex (6). The higher toxicity of PdeL (1) complex than PteL (6) happens because the ligand-exchange behavior of platinum compound is quite slow, which gives them a high kinetic stability and results in ligand-exchange reactions of minutes to days, rather than microseconds to seconds for many other coordination compounds.…”