title: Structure-activity relationship study of novel anticancer aspirin-based compounds.
abstract: We performed a structure-activity relationship (SAR) study of a novel aspirin (ASA) derivative, which shows strong anticancer activity in vitro and in vivo. A series of ASA-based benzyl esters (ABEs) were synthesized and their inhibitory activity against human colon (HT-29 and SW480) and pancreatic (BxPC-3 and MIA PaCa-2) cancer cell lines was evaluated. The ABEs that we studied largely comprise organic benzyl esters bearing an ASA or acyloxy group (X) at the meta or para position of the benzyl ring and one of four different leaving groups. The nature of the salicyloyl/acyloxy function, the leaving group, and the additional substituents affecting the electron density of the benzyl ring, all were influential determinants of the inhibitory activity on cancer cell growth for each ABE. Positional isomerism also played a significant role in this effect. The mechanism of action of these compounds appears consistent with the notion that they generate either a quinone methide or an m-oxybenzyl zwitterion (or an m-hydroxybenzyl cation), which then reacts with a nucleophile, mediating their biological effect. Our SAR study provides an insight into the biological properties of this novel class of compounds and underscores their potential as anticancer agents.
authors.affiliation: Division of Cancer Prevention, Department of Medicine, Stony Brook University, Health Sciences Center T17-080, Stony Brook, NY 11794-8173, USA.
authors.forename: Stancy
authors.initials: S
authors.lastname: Joseph
authors.forename: Ting
authors.initials: T
authors.lastname: Nie
authors.forename: Liqun
authors.initials: L
authors.lastname: Huang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.forename: Krishnaiah
authors.initials: K
authors.lastname: Atmakur
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Gupta
authors.forename: Francis
authors.initials: F
authors.lastname: Johnson
authors.forename: Basil
authors.initials: B
authors.lastname: Rigas
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001241:Aspirin / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D007536:Isomerism; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001241:Aspirin