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A method for the synthesis of 1-amino-3,3-dimethyl-3,4-dihydronaphthaline-2-carbonitrile (β-aminonitrile) was developed and used to synthesize Schiff bases, thioureide and chloracetamide derivatives. This latter was cyclized to 5,5-dimethyl-2-chloromethyl-5,6-dihydrobenzo[h]quinazoline-4(3H)-one, which was used to synthesize a series of 2-sulfanylmethyl and 2-aminomethyl derivatives. 2-Chloromethylbenzo[h]quinazoline in the presence of a base was found to form condensed heterocyclic compounds with seven rings: 1,1,11,11-tetramethyl-1,2,11,12-tetrahydropyrazino[2,1-b:5,4-b′]di(benzo[h]quinazoline)-10,16(8H,18H)-di one. The antitumor properties of the compounds synthesized here were studied in an ascites carcinoma model and the antibacterial properties were studied using the agar diffusion method.

3,4-Substituted-(4H)-1,2,4-triazole-5-thiols were synthesized and used for S-alkylation, cyanoethylation, and aminomethylation to produce a series of new 1,2,4-triazole derivatives of interest as biologically active compounds. The antitumor properties of several of the 1,2,4-triazole derivatives were studied.

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

A series of new 3,4,5-substituted 1,2,4-triazoles were synthesized. Their SH-alkylation by various alkylating compounds and aminomethylation leading to the formation of Mannich bases were studied. The influence of the synthesized compounds on the level of DNA methylation and their antitumor and antibacterial properties were investigated. Several compounds with pronounced demethylation and weak antitumor and antibacterial activities were identified. Correlations among the investigated biological properties were not found.

2-Sulfanyl-substituted 3-ethyl-3H-spiro[benzo[h]quinazolin-5,1-cyclohexane]-4(6H)-ones were synthesized by reacting 3-ethyl-2-thioxo-2,3-dihydro-1H-spiro[benzo[h]quinazolin-5,1-cyclohexane]-4(6H)-one with halides. 2-Hydrazino-3-ethyl-3H-spiro[benzo[h]quinazolin-5,1-cyclohexane]-4(6H)-one was prepared from 3-ethyl-2-methylthio-3H-spiro[benzo[h]quinazolin-5,1-cyclohexane]-4(6H)-one and transformed into 1-sulfanyl-substituted triazolobenzoquinazolines. Several of the synthesized compounds exhibited high anti-monoamine oxidase and antitumor activity.

Amides that cyclized into 2-substituted 3H-spiro[benzo(h)quinazoline-5,1′-cyclohexane]-4(6H)-ones were prepared by reaction of 4′-amino-1′H-spiro[cyclohexane-1,2′-naphthalene]-3′-nitrile with carboxylic acid chlorides. Substitution of the benzoquinazolines by alcoholates, secondary amines, and thiolates was investigated. Thus,2-(3-chloropropyl)-3H-spiro[benzo[h]quinazoline-5,1′-cyclohexane]-4(6H)-one underwent intramolecular cyclization to form 10,11-dihydro-5H-spiro[benzo[h]pyrrolo[2,1-b]quinazoline-6,1′-cyclohexane]- 7(9H)-one whereas 2-chloromethyl-3H-spiro[benzo[h]quinazoline-5,1′-cyclohexane]-4(6H)-one formed substitution products. The influence of the synthesized compounds on brain monoamine oxidase activity was studied in vitro. It was found that the majority of the compounds inhibited deamination of 5-HT. The antitumor activity of the compounds was studied using two grafted murine tumor models, i.e., Ehrlich ascites carcinoma and sarcoma 180. Some of the investigated compounds suppressed tumor growth by 50 – 56%.

Ethyl 2-cyano-3,3-dimethyl-4-phenylbutanoate was cyclized into 1-amino-3,3-dimethyl-3,4-dihydronaphthalene-2-ethylcarboxylate, condensation of which with isothiocyanates synthesized 3-substituted 5,5-dimethyl-2-thioxo-2,3,5,6-tetrahydrobenzo[h]quinazolin-4(1H)-ones. The antineoplastic properties of the synthesized compounds were studied.

3-Thio-4-phenyl-5-[2-(4-)benzyloxyphenyl]-1,2,4-triazoles were prepared by cyclization of the corresponding thiosemicarbazides in alkaline medium. The 2-N-substituted derivatives of the aforementioned triazoles were obtained via aminomethylation, cyanethylation, and alkylation of α-epoxides. 3-S-Substituted 1,2,4-triazoles were synthesized by alkylation with various aliphatic and aromatic halides. Acylhydrazides were prepared via reaction of 2-(4-)benzyloxybenzoic acid hydrazides with dicarboxylic acid anhydrides. The antitumor activity of the synthesized compounds was studied.

A series of new furyl-2-substituted derivatives of 1,3,4-thiadiazole and 1,2,4-triaozle have been synthesized. The S-alkylation and aminomethylation of the latter leading to their 3-mercapto- and 2-aminomethylene-substituted derivatives have been studied. Results of antitumor activity testing of the synthesized compounds are presented and discussed.

The condensation of 4-amino-3-cyano-1,2-dihydrospiro(naphthalene-2,1'-cyclopentane) with y-chlorobutyryl chloride and aromatic acid chlorides yielded amides that were cyclized into 2-substituted 4-oxo3,4,5,6-tetrahydrospiro(benzo[h]quinazoline-5,1'-cyclopentanes). Replacement of the chlorides by nucleophilic reagents (alkoxides, secondary amines, thiolates) was studied. It was established that 2-(y-chloropropyl)-4-oxo-3,4,5,6-tetrahydrospiro(benzo[h]quinazoline-5,1'-cyclopropane) underwent intramolecular cyclization to form 6-oxo-2,3,4,5,7,8-hexahydrospiro(benzo[h]pyrrolo[2,1-b]quinazoline-7,1'-cyclopentane) whereas 2-chloromethyl-4-oxo-3,4,5,6-tetrahydrospiro(benzo[h]quinazoline-5,1'-cyclopentane) formed substitution products. The antimonoamineoxidase and antineoplastic properties of the synthesized compounds were studied.

Reaction of 4-amino-3-ethoxycarbonyl-1,2-dihydrospiro(naphthalene-2,1'-cyclohexane) with allylisothiocyanate was used to synthesize 3-allyl-4-oxo-2-thioxo-1,2,3,4,5,6-hexahydrospiro(benzo[h]quinazoline5,1'-cyclohexane). Condensation of the latter with halides of various structure led to a series of 2-sulfanylsubstituted benzo[h]quinazolines. The antimonoaminooxidase and antineoplastic properties of the synthesized compounds were studied.

N'-{[(2-cyano-3-ethyl-3-methyl-3, 4-dihydronaphthalen-1-yl)amino]carbonothionyl}benzamide (II) was synthesized by reaction of 1-amino-3-ethyl-3-methyl-3,4-dihydronaphthalene-2-carbonitrile (aminonitrile I) with benzoylisothiocyanate. Condensation of aminonitrile I with phenylchloroformate yielded carbamate III, which was converted into mono-and disubstituted ureas IV and V via reaction with ammonia and aniline, respectively. A series of 2-substituted condensed triazolobenzoquinazolines (VI – XVI) was synthesized by condensation of carbamate III with hydrazides of aromatic and heteroaromatic carboxylic acids. The antineoplastic and antimonoamineoxidase properties of the synthesized compounds have been studied.

The physicochemical properties and antitumor activity of dacarbazine, its analogs, and the new alkylating agent imidazene are reviewed. It is shown that the activity of dacarbazine is superior to most of its analogs. Imidazene exhibits an advantage over dacarbazine with respect to both stability and activity and can be used for the treatment of malignant melanoma and sarcoma of soft tissues and in combined chemotherapy.

The interaction of 1-amino-3-methyl-3-ethyl-3,4-dihydronaphthaline-2-carbonitrile (I) with propanoic acid chloranhyride was used to synthesize the corresponding amidonitrile II, which was then cyclized to form 2,5-diethyl-5-methyl-4-oxo-5,6-dihydrobenzo[h]quinazolin-4(3H)-one (III). Interaction of aminonitrile I with triethylorthoformate and carboxylic acid hydrazides yielded 2-substituted 4-methyl-4-ethyl-4,5-dihydrobenzo[h][1, 2, 4] triazolo[1,5-c]quinazolines (IV-XVIII). The antitumor and anti-monoamine oxidase properties of the compounds obtained were studied.

Conditions for effective alkylation of new 3,4-substituted-5-mercapto-1,2,4-triazoles with various alkylating agents are established. Several compounds possessing pronounced antitumor activity have been found in experiments using two xenograft tumor models.

The interaction of 3-methyl-3-ethyl-1-amino-2-ethoxycarbonyl-3,4-dihydronaphthaline with phenyl-and phenethylisothiocyanates and subsequent treatment of the reaction mix with alkali led to the formation of the corresponding 3-phenyl-and 3-phenethyl-5-methyl-5-ethyl-4-oxo-2-thioxo-1,2,3,4,5,6-hexahydrobenzo[h]quinazolines (II, III). Condensation of the resulting 2-thioxobenzo[h]quinazolines II and III with halogenides of different structures was used to synthesize 2-sulfanyl-substituted 5-methyl-5-ethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines (IV–XXVII). Reaction of benzo[h]quinazoline II with 2-ethanolamine and 3-propanolamine yielded 5-methyl-5-ethyl-3-phenyl-2-(β-hydroxyethylamino)-and 5-methyl-5-ethyl-3-phenyl-2-(γ-hydroxypropylamino)-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines (XXVIII, XXIX) respectively. The effects of the resulting compounds on brain monoamine oxidase (MAO) activity were studied in in vitro experiments. Most of the compounds were found to inhibit 5-HT deamination. The antitumor activities of these compounds were studied using two models of grafted mouse tumors — Ehrlich ascites carcinoma (EAC) and sarcoma 180. Some of the study compounds had moderate therapeutic effects (suppressing tumor growth by 50–60%, p < 0.05).

Reactions of 3-methyl-3-ethyl-1-amino-2-cyano-3,4-dihydronaphthalene (I) with carboxylic acid chlorides lead to the formation of either monoacylated (II–VII) or diacylated (VIII–X) products depending on the amount of reactants. When dry hydrogen chloride is bubbled through alcohol solutions of the amides (II–VII), these compounds cyclize to 2-substituted 5-methyl-5-ethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines (XI–XVI). Alkylation of benzo[h]quinazolines XI and XII yielded 3-substituted benzo[h]quinazolines (XVII–XIX). Antitumor and antimonoamineoxidase properties of the synthesized compounds have been studied. Experiments in vitro have shown that some of these compounds exhibit antimonoamineoxidase activity. Compounds II and IV showed weak inhibition of Ehrlich’s ascites carcinoma (by 30 and 47%, respectively) at doses of 100–250 mg/kg in chemotherapeutic experiments.

4-Amino-3-cyano-1,2-dihydrospiro(naphathaline-2,1′-cyclohexane) (aminonitrile) was converted by interaction with p-tolyl acid chloranhydride into 4-(4-methylbenzoyl)amino-3-cyano-1,2-dihydrospiro(naphthaline-2,1′-cyclohexane) (II), which was subjected to cyclization to form 2-(p-tolyl)-4-oxo-3,4,5,6-tetrahydrospiro(benzo[h]quinazoline-5,1′-cyclohexane) (III). This aminonitrile was converted, using a known method, to 4-ethoxymethyleneimino-3-cyano-1,2-dihydrospiro(naphthaline-2,1′-cyclohexane) (IV). Compound IV was condensed with hydrazides of aromatic, alkylaromatic, and alkoxyaromatic acids in dimethylformamide, producing 5-substituted 7,8-dihydrospiro(benzo[h]triazolo[2,3-c]quinazolines) (Va-v) at high yield. The antitumor properties of the resulting compounds were studied using two models of grafted mouse tumors-Ehrlich ascites carcinoma (EAC) and sarcoma 180. Anumber of the newly synthesized compounds had, along with moderate acute toxicity, marked antitumor activity in experimental conditions.

Micronuclear and antitumor activities of two newly synthesized iodides of pyrazolo[1,5a]pyrimidines were investigated using mice model. It has been shown that both compounds are slightly toxic and have no antitumor activity in mice with Ehrlich's ascites carcinoma. Only one of them has weak micronuclear activity. Both compounds increase substantially micronuclear as well as antitumor activities of cyclophosphamide.

A series of new derivatives of benzo[h]quinazolines containing diethyl substituents at position 5 were synthesized. The alkylation of some 2-substituted 5,5-diethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines with methyl iodide led to N-substituted products, while a similar reaction with ethyl iodide led to a mixture of N-substituted and O-substituted products. Some of the synthesized 5,5-diethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines exhibit pronounced antiaminooxidase and weak antitumor properties.

9-Methyl-9-ethyl-8-oxo-2,3,4,5,6,7,9,10-octahydrobenzo[h]azepino[2,l-b]quinazoline was obtained via the interaction between 1-amino-3-methyl-3-ethyl-2-ethoxycarbonyl-3,4-dihydronaphthalene (aminoester) and caprolactam in the presence of phosphorus oxychloride. 5-Methyl-5-ethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazoline was synthesized using the reaction of aminoester with formamide under the conditions of the Niementowski reaction. This aminoester reacts with benzoyl isothiocyanate at room temperature with the formation of an N′-benzoylthioureido derivative, which exhibits cyclization in the presence of an alkali, yielding 5-methyl-5-ethyl-4-oxo-2-thioxo-1,2,3,4,5,6-hexahydrobenzo[h]quinazoline. The latter is converted into 2-substituted 5-methyl-5-ethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines by reactions with alkyl-, allyl-, benzyl-and metalylhalogenides, 2-bromoethanol, chloroacetic acid ester, and amides of halogen-substituted acetic acids. The effect of the synthesized compounds on monoamine oxidase (MAO) activity in vitro, and the antitumor properties of some compounds in vivo were evaluated. It is established that most compounds exhibit significant antitumor and anti-MAO activity.

The nanotechnology offers some exciting possibilities in cancer treatment, including the possibility of destroying tumors with minimal damage to healthy tissue and organs by targeted drug delivery systems. Considerable achievements in investigations aimed at the use of ZnO nanoparticles and nanocontainers in diagnostics and antitumor therapy were described. However, there are substantial obstacles to the purposes to be achieved by the use of zinc oxide nanosize materials in antitumor therapy. Among the serious problems are the techniques of obtaining ZnO nanosize materials. The article presents a new vector delivery system for the known antitumor drug, doxorubicin in the form of polymeric (PEO, starch-NaCMC) hydrogels, in which nanosize ZnO film of a certain thickness are deposited directly on the drug surface on glass substrate by DC-magnetron sputtering of a zinc target. Anticancer activity in vitro and in vivo of those nanosize zinc oxide composites is shown.

The initial reagents were (3-methyl-4-alkoxybenzyl)malonates (I) obtained by reaction of the corresponding 3-methyl-4-alkoxybenzyl chlorides with malonic ester in the presence of sodium ethylate; the procedure was analogous to that described in [2]. Subsequent cyclization of the substituted malonic esters I with thiourea or guanidine hydrochloride in anhydrous ethanol in the presence of sodium ethylate led to the formation of pyrimidines II or III. Here, an important factor is the amount of sodium ethylate. It was established that 2-mercapto- and 2-amino-4,6-dihydroxypyrimidines II and III can be obtained with high yields only if two or three equivalents of sodium ethylate, respectively, are employed. Pyrimidines II were converted into methylthio derivatives IV by reaction with methyl iodide in a methanol solution of potassium hydroxide. The purity and identity of compounds II – IV were checked by TLC. The proposed structures were confirmed by data of the IR, 1 H NMR, and mass spectroscopy.

The antitumor properties of 2-imidazolinyl-2-hydrazones of acetophenones with various substituents in the benzene ring have been studied. High activity is found for 4-amyloxy-3-nitroacetophenone 2-imidazolinyl-2-hydrazone, which points to the expediency of its further investigation.

Reactions of 2-methylthio-4,6-dichloro-5-(4-alkoxybenzyl)pyrimidines with aliphatic and aromatic primary and secondary amines and sodium methoxide were used to synthesize the corresponding 4-amino-and 4-methoxy-6-chloropyrimidines. The antitumor properties of the synthesized compounds have been studied.

Methods for the synthesis of new heterosystems of condensed thieno[3,2-d]-1,2,3-triazines on the basis of pyrido[2,3-b]thiophenes have been developed. The antitumor activity of the synthesized compounds was studied and several compounds possessing low toxicity and moderate antitumor activity were found.

3-Benzofuryl-4-benzyl(cyclohexyl)-5-mercapto-1,2,4-triazoles were synthesized by cyclization of the corresponding substituted thiosemicarbazides. 5-Mercaptotriazoles were S-alkylated with various alkenyl-substituted benzylhalogenides, chloracetamide, chloroacetic, and α-bromopropionic and α-bromocaproic acids. The aminomethylation and hydroxymethylation reactions of 3-benzofuryl-4-benzyl(cyclohexyl)-5-mercapto-1,2,4-triazoles were studied. The antitumor activity of the resulting compounds was investigated.

New 2-S-4,5,6-substituted pyrimidines have been prepared via the reaction of 2-mercaptopyrimidines with allyl-, methallyl-, and substituted-benzyl chlorides, chloroacetamide, and chloracetic, a-bromopropionic, and a-bromocaproic acids. Reactions of 2-methylthio-derivatives with morpholine, piperidine, and o- and p-anisidines yielded the corresponding 2-amino-derivatives. The antitumor properties of the synthesized compounds have been studied.

Bis(2-chloroethyl)amino derivatives of imidazole, 4(5)-aminoimidazol-5(4)-carboxamide, 4-nitro-5-thioimidazole, benzimidazole, and imidazolylpeptides are reviewed. Data are presented for active compounds, some of which have passed the preclinical testing stage. Structures under consideration are interesting with respect to both the search for new antitumor drugs and the synthesis of compounds with different biological properties.

A series of 3-benzofuryl-4-phenyl(allyl)-5-mercapto-1,2,4-triazoles have been synthesized by cyclization of the corresponding substituted thiosemicarbazides of benzofuran-2-carboxylic acid. S-alkylation of 5-mercaptotriazoles with various alkyl-, alkenyl-, and benzyl-substituted benzyl chlorides; chloroacetamides; and chloroacetic-, 2-bromopropionic-, and 2-bromocaproic acids has been studied. The antitumor activity of the synthesized compounds was tested.

A series of new 2-S-substituted pyrimidine derivatives has been synthesized via the interaction of 2-mercaptopyrimidines with various alkylbromides, chloracetamide, and unsubstituted and substituted benzyl chlorides. The synthesized compounds have been tested with respect to antitumor activity.

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.