Synthesis and evaluation of anti-Toxoplasma gondii and antimicrobial activities of thiosemicarbazides, 4-thiazolidinones and 1,3,4-thiadiazoles.

In this work we reported the synthesis and evaluation of anti-Toxoplasma gondii and antimicrobial activities in vitro of three new compound series obtained from ethyl(5-methyl-1-H-imidazole-4-carboxylate): acylthiosemicarbazide analogues 3a-d, 4-thiazolidinone analogues 4a-d and 1,3,4-thiadiazole analogues 5a-d. All synthesized compounds were characterized by IR, (1)H, (13)C NMR and HRMS. The majority of the tested compounds show excellent anti-T. gondii activity when compared to hydroxyurea and sulfadiazine. In addition it was also shown that most of the compounds in this study have a better performance against intracellular tachyzoites. The results for antimicrobial activity evaluation showed weak antibacterial and antifungal activities for all the tested molecules, when compared with the standard drugs (chloramphenicol and rifampicin for antibacterial activity; nistatin and ketoconazole for antifungal activity).

Synthesis, anti-Toxoplasma gondii and antimicrobial activities of benzaldehyde 4-phenyl-3-thiosemicarbazones and 2-[(phenylmethylene)hydrazono]-4-oxo-3-phenyl-5-thiazolidineacetic acids.

In the present communication, a new series of 2-[(phenylmethylene)hydrazono]-4-oxo-3-phenyl-5-thiazolidineacetic acids (2a-p) have been synthesized. Benzaldehyde 4-phenyl-3-thiosemicarbazones substituted (1a-p) were also obtained and used as intermediate to give the title compounds. All synthesized compounds were characterized by IR, (1)H and (13)C NMR. The in vitro anti-Toxoplasma gondii activity of 1a-p and 2a-p was evaluated. The 4-thiazolidinones (2a-p) were screened for their in vitro antimicrobial activity. For anti-Toxoplasma gondii activity, in general, all compounds promoted decreases in the percentage of infected cells leading to parasite elimination. These effects on intracellular parasites also caused a decrease in the mean number of tachyzoites. In addition, most of the 4-thiazolidinones showed more effective toxicity against intracellular parasites, with IC(50) values ranging from 0.05 to 1 mM. According to results of antimicrobial activity, compounds 2f, 2l, and 2p showed best activity against Mycobacterium luteus, 2c was more active against Mycobacterium tuberculosis, and 2g, 2l, and 2n showed same activity as nistatin (standard drug) against Candida sp. (4249).

Synthesis of thiosemicarbazone and 4-thiazolidinone derivatives and their in vitro anti-Toxoplasma gondii activity.

Thiosemicarbazone and 4-thiazolidinone derivatives were synthesized in one and two step, respectively, from thiosemicarbazide, in satisfactory yields. Then, the synthesized compounds were submitted to evaluation against host cells infected with Toxoplasma gondii. The present studies showed that thiosemicarbazones 2 and 4-thiazolidinone derivatives 3 were effective against intracellular T. gondii.

Synthesis of indolizidines and pyrrolizidines through the [2 + 2]cycloaddition of five-membered endocyclic enecarbamates to alkyl ketenes. Unusual regioselectivity of Baeyer-Villiger ring expansions of alkyl aza-bicyclic cyclobutanones.

The total syntheses of two indolizidine skeletons and of the necine base (+/-)-platynecine were accomplished in a concise manner with good overall yields starting from a common five-membered endocyclic enecarbamate. These syntheses feature a [2 + 2]cycloaddition of the five-membered endocyclic enecarbamate 5 to alkylketenes that proceeded in high yields and with high stereoselectivity to provide an endo alkyl cycloadduct as the major or only product. The minor exo alkyl cycloadducts, which can be observed in some [2 + 2]cycloadditions, seem to derive from the endo cycloadduct, the putative kinetic product, by epimerization. An unusual regioselectivity was observed for the Baeyer-Villiger oxidation of 7-alkyl-2-azabicyclic cyclobutanones. Endo-7-alkyl cycloadducts ring-expanded exclusively to a gamma-lactone in which oxygen is inserted into the C6-C7 bond in preference to the bridgehead C5-C6 bond. With the exo-7-alkyl cycloadduct the regioselectivity of the Baeyer-Villiger oxidation is drastically reduced, leading to mixtures of regioisomeric lactones in a ratio of approximately 1.5 to 1. It is hypothesized that the steric strain built into the Criegee cyclobutane intermediate is the regioselective controlling factor in these oxidations, overriding any stereoelectronic bias for ring expansion. A rationale for the mechanism of the [2 + 2]cycloaddition involving enecarbamates and ketenes is presented, which seems to involve the participation of an N-acyliminium-enolate intermediate.