Synthesis of novel α-santonin derivatives as potential cytotoxic agents

Abstract

Ten novel α-santonin derivatives have been synthesized as cytotoxic agents. The in vitro antitumor activity of these compounds has been evaluated against cancer cells lines. Structure-activity relationships indicate that α-methylene-γ-lactone and endoperoxide functionalities play important roles in conferring cytotoxicity. The compounds 2-4, possessing the α-methylene-γ-lactone group showed IC50 values between 5.70 and 16.40 μM. Mixture of isomers 5 and 6, with the α-methylene-γ-lactone and endoperoxide functionalities, displayed the greatest activity, with IC50 values between 1.45 and 4.35 μM. The biological assays conducted with normal cells revealed that the compounds 2, 5 and 6 are selective against cancer cells lines tested. Bioactive lactones described herein and in our previous report did not cause disruption of the cell membrane in mouse erythrocytes.

Synthesis and evaluation of new α-methylene-γ-lactone carbamates with NO production inhibitory effects in lipopolysaccharide-induced RAW 264.7 macrophages

“…These different activities have been ascribed to be dependent on the a-methylene-g-lactone functionality, which is prone to proceed a Michael addition reaction with some nucleophiles, e.g., cysteine thiol groups [12][13][14][15]. The activity of these compounds is tightly related to their inhibitory effect on many thiol-containing enzymes [16,17].…”

A quantum chemical and chemometric study of sesquiterpene lactones with cytotoxicity against tumor cells

“…The semi-empirical PM6 method was employed to calculate atomic and molecular descriptors of 20 SQLs reported in our previous works [16,28] as cytotoxic agents.…”

“…Continuing our efforts to prepare compounds with high cytotoxic activity [16,18,[23][24][25][26][27], we describe herein a study of the relationship between selected molecular parameters (descriptors) and cytotoxicity of a set of SQLs. The semi-empirical PM6 method was employed to calculate atomic and molecular descriptors of 20 SQLs reported in our previous works [16,28] as cytotoxic agents.…”

New Selenoderivatives as Antitumoral Agents

“…This hypothesis has been corroborated in other tumoral cell lines. In addition, the bioactive α-santonin derivatives are selective against cancer cells (Arantes et al, 2010). It is well established that various human diseases, including PC, are associated with a disturbed intracellular redox balance and oxidative stress (OS).…”