Design and synthesis of spirotryprostatin-inspired diketopiperazine systems from prolyl spirooxoindolethiazolidine derivatives

Synthesis, in Vitro, and in Cell Studies of a New Series of [Indoline-3,2′-thiazolidine]-Based p53 Modulators

“…In these conditions, all final products ( 4a – f and 4h – q ) were obtained as single diastereomers in 32–58% overall yields. These stereoselectivities in the acylation reactions of thiazolidine derivatives have been previously observed by us and other authors and can be explained by the fact that thiazolidines undergo facile ring opening and closure reactions. This favors the formation of thermodynamically more stable diastereoisomers.…”

“…Starting spirooxoindolethiazolidine skeletons ( 13 – 18 ) were constructed by condensation between the isatin derivatives ( 7 – 12 ) and cysteine ethyl ester in EtOH. These derivatives were obtained with 80–90% yields, as (2′ R )/(2′ S ) epimeric mixtures ranging from 60/40 to 40/60 ratios as we previously described. , The 3′ - acyl derivatives were obtained by reaction of compounds 13 – 18 with the corresponding 2-(4-chlorophenyl)acetyl, 4-chlorobenzoyl, 4-methylbenzoyl, benzoyl, or cyclohexanecarbonyl chlorides in THF using TEA as base.…”

“…ESIMS experiments were performed on an Applied Biosystem API 2000 triple-quadrupole spectrometer. Starting spiro(oxoindolethiazolidine) ethyl ester derivatives ( 13 – 18 ) were synthesized as described in refs and . As an example, here we described the synthesis of (3 RS ,4′ R )-ethyl 5-bromo-1-methyl-2-oxospiro[indoline-3,2′-thiazolidine]-4′-carboxylate ( 18 ).…”

Identification of the Spiro(oxindole-3,3′-thiazolidine)-Based Derivatives as Potential p53 Activity Modulators

“…On the basis of these findings and on identification of new activators of p53 pathway in tumor cells, we have designed and synthesized two focused libraries of compounds based on the spiro(oxindole-3,3′-thiazolidine) nucleus, a structural analogue of spirooxoindole pyrrolidine template . Recently, we have described the use of this template to construct new heterocyclic systems designed as potential modulators of cell cycle . In this context, the 3′,4′ hydantoin derived tetracyclic nucleus has turned out to be a very easily derivatizable scaffold.…”

Antimycobacterial activity of spirooxindolo-pyrrolidine, pyrrolizine and pyrrolothiazole hybrids obtained by a three-component regio- and stereoselective 1,3-dipolar cycloaddition

“…For instance, coerulescine, 10 the simplest spirooxindole-pyrrolidine hybrid found in nature, displays local anesthetic effect, pteropodine modulates the function of muscarinic serotonin receptors. 11 The spirotryprostatins have antimitotic properties and are of interest as anticancer lead compounds, 12 and the recently discovered small-molecule MDM2 inhibitor MI-219 and its analogues are in advanced preclinical development for cancer therapeutics (Fig. 1).…”