Structure‐activity Relationships of Alkylating Agents in Cancer Chemotherapy*

Frontier Orbitals in Chemical and Biological Activity: Quantitative Relationships and Mechanistic Implications*

“…Q N H ϭ HOMO electron density on the aniline mustard nitrogen atom ED 90 ϭ effective dose (µM/kg) required for 90% inhibition of Walker 256 carcinoma [79,80] a Equation (2) data were forced through the origin such that (0, 0) is included as data for point 12. (2), Table 18].…”

Identification of oxidized protein hydrolase as a potential prodrug target in prostate cancer

“…As indicated in Figure 1, the esterase prodrug strategy utilizes pharmacological compounds that are blocked by esterification but are activated when cancer cell esterases cleave the ester bond and release the active drug [11]. A degree of specificity can be achieved if the cancer cell esterase is overexpressed compared to normal tissue.…”

Reactions of 2,2-dimethylaziridine-type Alkylating Agents in Biological Systems I: Colorimetric Estimation and Stability in Physiological Media

“…These results suggest continuing interest in the clinical study of this agent. In the meantime, several other compounds containing the 2,2-dimethylaziridine moiety were synthesized and found to be effective against a spectrum of transplanted tumors in rodents (21)(22)(23)(24)(25)(26). Two of these agents, ethyl bis(2,2-dimethyl-l-aziridinyl)phosphinate (11) (23,24) and tris(2,2-dimethyl-l-aziridinyl)phosphine oxide (111) (25), which showed particularly potent activities against leukemia L-1210 in mice, passed through the preclinical pharmacology stage (24) and are presently undergoing preliminary evaluation against solid tumors in man.…”

“…In view of the unique chemical and pharmacological properties (2,7,8,22,26) of these 2,2-dimethylaziridine derivatives as compared to their ring-C-unsubstituted aziridine analogs [i.e., the conventional "ethyleniminetype" alkylating agents, bis( 1 -aziridinyl)phosphinylurethan (IV), triethylenemelamine (V), tris( 1-aziridiny1)-phosphine oxide (VI), etc.] and in view of their apparently selective chemotherapeutic effects (26), it appeared worthwhile to investigate the reactions of these compounds in biological systems.…”

“…and in view of their apparently selective chemotherapeutic effects (26), it appeared worthwhile to investigate the reactions of these compounds in biological systems. Such studies may lead to a better understanding of the chemical, metabolic, and pharmacokinetic processes influencing the chemotherapeutic activities of these unusually "waterlabile" alkylating agents.…”