T. R. Ovsepyan

Synthesis and Antitumor Activity of New Methylglyoxal and Glucosone Bisthiosemicarbazones and Their Copper Complexes

I, II: R = C3H7 (a), i-C3H7 (b), C4H9 (c), CH3 (d), C2H5 (e, g), C4H9 (f); R = CH3 (a – e), (CHOH)3CH2OH (f, g); X = H (a – c, f), NO2 (d), Cl (e, g). The initial substituted thiosemicarbazides were synthesized as described previously [5]. Bisthiosemicarbazones Ia – Ig were obtained using reactions of these compounds with methylglyoxal and glucosone [3]; the products were identified by TLC, elemental analyses, and IR and UV spectroscopy. In the next stage, compounds Ia – Ig interacted with equimolar amounts of copper sulfate to yield the corresponding copper bisthiosemicarbazones IIa – IIg. The products appeared as crystalline substances of red color, soluble in DMSO, DMF, and some other organic solvents. The proposed structures of the synthesized compounds were confirmed by measuring their spectrophotometric characteristics in the visible range, by the data of spectrophotometric titration, and by comparison with the properties of analogous complexes with structures refined using EPR data [1 – 3]. Two bisthiosemicarbazones (Ie, Ig) and their copper complexes (IIe, IIg), containing the same substituents in the benzene ring, were characterized by distribution coefficients (K d ) in the octanol – water system. It was established that the lipophilicity of methylglyoxal bisthiosemicarbazone (Ie) is higher than that of glucosone bisthiosemicarbazone (Ig), while the copper complexes of both bisthiosemicarbazones possess almost equal lipophilicities. It was established that the synthesized methylglyoxal bisthiosemicarbazones and their copper complexes Ib – Id, IIb – IId possess low acute toxicities (LD 10

Synthesis and pharmacological activity of new 1,4-substituted thiosemicarbazides

The initial compounds for the syntheses were 3-bromo-4-alkoxyphenylacetic acid hydrazides obtained using reactions between methyl esters of the corresponding acids and hydrazine hydrate [3]. The substituted benzylisothiocyanates were synthesized by reacting the corresponding benzyl chlorides with potassium rhodanate [4]. The target thiosemicarbazides I IX had the form of crystalline substances and were identified by TLC and by IR and UV spectroscopy (Table 1). The acute toxicity tests with the synthesized compounds showed that the maximum tolerated doses (MTD) exceed 2000 mg/kg, which allowed the chemotherapy tests on sar-

Synthesis and hypoglycemic activity of new thiosemicarbazide derivatives

Previously we have demonstrated that substituted EXPERIMENTAL CHEMICALPART thiosemicarbazides possess pronounced hypoglycemic activity [I]. In this work, we have studied the hypoglycemic propThe lH NMR spectra were measured on a Varian T-60 erties of several thiosemicarbazones (I III) synthesized earspectrometer using TMS as the internal standard. The meltlier in the search for antitumor agents [2 4] and a series of ing temperatures were determined using a Boetius micronew thiosemicarbazones (IV XV) obtained by reactions of scopic heating stage. TLC chromatograms were obtained on 4-alkoxybenzylthiosemicarbazides with substituted acetophenones.

Synthesis and Antitumor Properties of New 1,2,4-Triazoles and 1,3,4-Thiadiazoles

New S-substituted derivatives were synthesized via alkylation of mercapto-substituted 1,2,4-triazoles and 1,3,4-thiadiazoles by various aliphatic and aromatic halides. Aminomethylation of 5-thio-1,2,4-triazoles formed the corresponding Mannich bases. The antitumor properties of the synthesized compounds against sarcoma 37 and EAC grafted tumor models and their influence on DNA methylation were studied

Synthesis and antitumor activity of copper complexes of 4-alkoxybenzyl-substituted thiosemicarbazones of aromatic aldehydes

Previous investigations of the properties of thiosemicarbazones of monocarbonyl compounds and their complexes with copper(II) ions showed that some of the compounds (in particular, the derivatives of anisaldehyde and vaniline) exhibit pronounced antimalignant activity with respect to experimental tumors [1, 2]. It was interesting to study how the second methoxy group introduced into the aromatic ring of the aldehyde component would influence the antittunor properties. The new compounds were synthesized by the following scheme:

Structure of 4-methoxybenzylguanidine sulfate—A new monoamine oxidase inhibitor

In searching for effective pathways for the synthesis of methoxybenzylguanidine sulfate (I), a new brain monoamine oxidase (MAO) inhibitor of delayed action [1], it was established that compound I was originally described by Saijo [2] as having m.p. = 210-212~ (Ia), while a later work [3] reported m.p. = 215-216~ When we reproduced the reactions used in these works, it was found that the product with m.p. = 215 -216~ is not an individual compound, but represents a mixture of two compounds with m.p. = 210-212~ (Ia) and 234-235~ (Ib) [4]. Moreover, 4-methoxybenzylguanidine sulfate synthesized by our method, excluding the formation of isomer mixtures, also had m.p. = 234 235~ and possessed other physicochemical parameters identical to compound Ib.

Synthesis and antitumor activity of new 4-substituted thiosemicarbazones of some aldehydes

In continuation of the search for new pharmacologically active compounds in the series of thiosemiearbazones [I -5 ] , we have synthesized a series of substituted thiosemiearbazones of acetaldehyde, isobutyrie alhehyde and 4-hydroxy-3nitrobenzaldehydes and studied their andtumor activity. The properties of the new compounds were compared to those of a series of similarly substituted hydrazones obtained previously [6] on the basis of the same aldehydes. The initial 4-(3-X-4-alkoxybenzyl)thiosemicarbazides were obtained from the corresponding substituted benzylthioeyanates, synthesized by the method described in [7]. Interaction of the substituted thiosemiearbazides with aldehydes in an alcohol medium led to the corresponding thiosemiearbazones I XV. The substances were identified by the results of elemental analyses, and the proposed structures were confumed by the IR and UV data (for example, the IR spectra exhibited characteristic absorption bands due to the vibratious of C=N groups in the region of 15301510 era-l).

Synthesis and antimonoamineoxidase activity of 4-methoxybenzylguanidine and its sulfate

4-Methoxybenzylguanidine and its sulfate were patented as monoamine oxidase (MAO) inhibitors [1]. However, our attempts to develop efficient synthetic pathways revealed that the physicochemical characteristics available in the literature concerning the structure of these compounds differ from our data and are mutually contradictory. For example, the original work of Saigo [2] reported m.p. =210-212~ for 4methoxybenzylguanidine sulfate, while the later work [3] indicated 2 1 5 216~ [3]. When we reproduced the reaction pathway from [3] (scheme 1), it was found that the product I with m.p. = 215-216~ (I) is not an individual compound but represents a mixture of two guanidine derivatives with m.p. =210-212~ (Ia) and 234-235~ (Ib). It was suggested that the stage ofanisole chloromethylation involved in scheme 1 leads to the formation of an admixture of 2methoxybenzyl chloride besides the main product, 4methoxybenzyl chloride. As a result, the final product also comprises a mixture of two isomers, 2and 4-methoxybenzylguanidine sulfates. Scheme 1

Synthesis and antitumor activity of new thiosemicarbazones of salicylaldehyde and 4-diethylaminobenzaldehyde

Previously we reported on the synthesis of new bisthiosemicarbazones of methylglyoxal, 3-ethoxy-2-oxo-butanal, and glucosone, possessing pronounced antitumor activity [ t -4 ] . In continuation of that work, we have synthesized new substituted thiosemicarbazones on the basis of salicylaldehyde and 4-diethylaminobenzaldehyde and studied their antitumor properties. The synthesis was performed according to the following scheme:

Synthesis and antitumor activity of substituted thiosemicarbazones of heterocyclic carboxaldehydes and their chelates with transition metal ions

We synthesized new copper complexes of 4-methyl-, 4-phenyl-, 4-(4-alkoxybenzyl)-substituted thiosemicarbazones of 2-formylfuran and 2,2-dimethyl-4-formyltetrahydropyran. We discuss the spectral data and compare the antitumor properties of the ligands and complexes. The ligands were found to have a high therapeutic efficacy.