Functionalized 1,3-Thiazolidin-4-Ones from 2-Oxo-Acenaphthoquinylidene- and [2.2]Paracyclophanylidene-Thiosemicarbazones

The reactions of dialkyl acetylenedicarboxylates with various 2-oxo-acenaphthoquinylidene- and 4-acetyl[2.2]paracyclophanylidene-thiosemicarbazones were investigated. Using simple experimental procedures, 1,3-Thiazolidin-4-ones derived from acenaphthequinone or [2.2]paracyclophane were obtained as major products in good yields. In the case of allyl derivative of acenaphthoquinylidene-thiosemicarbazones, a complex structure of tetramethyl 5-(2-(((Z,E)-N-allyl-N′-(2-oxoacenaphthylen-1(2H)-ylidene)carbamohydrazonoyl)thio)-1,2,3-tris-(methoxycarbonyl)-cyclopropyl)-4-methoxy-7-oxabicyclo[2.2.1]hepta-2,5-diene-1,2,3,6-tetracarboxylate was formed. Single crystal X-ray analysis was used as an efficient tool to confirm the structure of the synthesized compounds as well as different spectroscopic data (1H-NMR, 13C-NMR, 2D-NMR, mass spectrometry and elemental analysis). The mechanism of the obtained products was discussed.

A cross-metathesis approach to novel pantothenamide derivatives

Pantothenamides are known for their in vitro antimicrobial activity. Our group has previously reported a new stereoselective route to access derivatives modified at the geminal dimethyl moiety. This route however fails in the addition of large substituents. Here we report a new synthetic route that exploits the known allyl derivative, allowing for the installation of larger groups via cross-metathesis. The method was applied in the synthesis of a new pantothenamide with improved stability in human blood.

Intramolecular carbenoid ylide forming reactions of 2-diazo-3-keto-4-phthalimidocarboxylic esters derived from methionine and cysteine

Methionine, S-benzylcysteine and S-allylcysteine were converted into 2-diazo-3-oxo-4-phthalimidocarboxylic esters 8a–c in three steps. Upon rhodium-catalysed dediazoniation, two intramolecular carbenoid reactions competed, namely the formation of a cyclic sulfonium ylide and that of a six-ring carbonyl ylide. The S-methyl and S-benzyl ylides 12a and b could be isolated, while S-allyl ylide 12c underwent a [2,3]-sigmatropic rearrangement. The short-lived carbonyl ylides derived from methionine and S-benzylcysteine formed head-to-tail dimers by a [3 + 3]-cycloaddition and could be trapped with external dipolarophiles, while the S-allyl derivative 14c yielded the pentacyclic compound 17 by an intramolecular [3 + 2]-cycloaddition reaction.

The Antileukemic Potential of New Derivatives of 5-Fluoro-1H-Indole-2,3-Dione-3-Thiosemicarbazone on in Vitro Cell Lines

1H-Indole-2,3-dione (isatin) is an endogenous compound identified in many organisms, possesses a wide range of biological activities. Biological properties of isatin include a range of actions in brain and offer protection against certain types of infections. This molecule has a versatile moiety that displays diverse biological activities, including anticancer activity. The discovery of numerous biologically active 3-substituted 2-indolinones led in the past decade to extensive synthesis of related compounds and as a result, anticancer agents were developed. In particular, among the 5-substituted analogs tested in the growth inhibitions against several human cancer cell lines, 5-halide, methoxy and trifluoromethoxy groups containing 3-substituted 2-indolinones show high antiproliferative effects. For this purpose, we first synthesized twelve 5-fluoro-1H-indole-2,3-dione-3-thiosemicarbazones that antituberculosis activities were shown previously by our teamwork and we researched anticancer drug potential in this study. The cytotoxic effects of twelve thiosemicarbazone derivatives were investigated by MTT assay in chronic myeloid leukemia cell lines (K562, HL60), B-lymphoma cell lines (P3HR1) and in vincristine resistant forms. The IC50 values (IC50 is a concentration that kills 50% of cells) were calculated from dose-response curve according to cytotoxicity index. The effectiveness of thiosemicarbazone derivatives were evaluated by comparing IC50 values in leukemic cell lines. All of the compounds were found cytotoxic in B-lymphoma cell lines (P3HR1, P3HR1Vin) in range 0.95–2.41 μM. However, the allyl derivative of thiosemicarbazones has cytotoxic activity in all the cancer cell lines (K562, K562Vin, HL-60, P3HR1, P3HR1Vin) that were tested. As a result, 5-fluoro-1H-indole-2,3-dione-3-thiosemicarbazones derivates might have chemotherapeutic drug potential in B-lymphoma patients. The allyl derivative of thiosemicarbazones has benefit both B-lymphoma and chronic myeloid leukemia patients in a large spectrum.