ABSTRACT
Epoxidation of argentilactone (1) with m-chloroperbenzoic acid gave a diasteromeric mixture of 2 and 3 in a ratio 1.8 : 1, with total yield 60%. The configuration of 7,8-oxirane ring for both diasteromers was determined by NMR analysis. Reaction of 1 with urea hydrogen peroxide gave the 3,4-epoxide (4) in 65% yield. The in vitro activity of 2, 3, 4 and argentilactone against Leishmania amazonensis was tested, only epoxides (2) and (3) showed leishmanicidal effect.
Subject(s)
Antiprotozoal Agents/pharmacology , Epoxy Compounds/chemistry , Epoxy Compounds/pharmacology , Lactones/chemistry , Lactones/pharmacology , Leishmania/drug effects , Animals , Molecular StructureABSTRACT
The Diels-Alder reaction between two polygodial-derived dienes and simple quinones to yield substituted naphtho- and anthraquinones, is described. The in vitro trypanocide activity for the series was determined. Two of the new compounds showed an activity ten and two times higher, respectively, than nifurtimox and benznidazole, the medicines of choice for the treatment of the acute Chagas' disease.
Subject(s)
Quinones/chemical synthesis , Quinones/pharmacology , Sesquiterpenes/chemical synthesis , Sesquiterpenes/pharmacology , Trypanocidal Agents/chemical synthesis , Trypanocidal Agents/pharmacology , Animals , Inhibitory Concentration 50 , Nifurtimox/pharmacology , Nitroimidazoles/pharmacology , Polycyclic Compounds/chemical synthesis , Polycyclic Compounds/pharmacology , Polycyclic Sesquiterpenes , Quinones/chemistry , Sesquiterpenes/chemistry , Trypanocidal Agents/chemistry , Trypanosoma cruzi/drug effects , Trypanosoma cruzi/growth & developmentABSTRACT
The synthesis of tetracyclic quinones 10a,b, 14a,b, 19a,b and 20a,b is described. The preparations involve regioselective Diels-Alder reactions via trapping the thiazole o-quinodimethane 9 with several benzofuranquinones and benzothiophenequinones. The structure of the regioisomers was assigned through 2D NMR 1H-13C HMBC experiments performed on 10a and 14a. Compounds 10a,b, 14a as well as phenol 1 and the starting quinones 2, 5, 7 and 15 are evaluated against Leishmania sp., Toxoplasma gondii and THP-1 cells. Almost all the tested compounds exhibit significant antiprotozoal activities with lower cytotoxicities than the reference compounds. Among them, quinones 2 and 14a possess the best activities towards L. donovani and T. gondii with the lowest toxicities.