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The present work reports the synthesis and evaluation of the antitumour and immunomodulatory properties of new phthalimides derivatives designed to explore molecular hybridization and bioisosterism approaches between thalidomide, thiosemicarbazone, thiazolidinone and thiazole series. Twenty-seven new molecules were assessed for their immunosuppressive effect toward TNFα, IFNγ, IL-2 and IL-6 production and antiproliferative activity. The best activity profile was observed for the ( 6a–f ) series, which presents phthalyl and thiazolidinone groups. [ABSTRACT FROM AUTHOR]

We modified the thiazolidinic ring at positions N3, C4,and C5,yielding compounds 6–24. Compoundswith a phenyl at position N3, 15–19, 22–24, exhibited better inhibitoryproperties for cruzain and against the parasite than 2-iminothiazolidin-4-one 5. We were able to identify one high-efficacy trypanocidalcompound, 2-minothiazolidin-4-one 18, which inhibitedthe activity of cruzain and the proliferation of epimastigotes andwas cidal for trypomastigotes but was not toxic for splenocytes. Havinglocated some of the structural determinants of the trypanocidal properties,we subsequently wished to determine if the exchange of the thiazolidinefor a thiazole ring leaves the functional properties unaffected. Wetherefore tested thiazoles 26–45andobserved that they did not inhibit cruzain, but they exhibited trypanocidaleffects. Parasite development was severely impaired when treated with 18, thus reinforcing the notion that this class of heterocyclescan lead to useful cidal agents for Chagas disease. [ABSTRACT FROM AUTHOR]