In vitro cytotoxic activities of 2-alkyl-4,6-diheteroalkyl-1,3,5-triazines: new molecules in anticancer research

The cytotoxic activities of new 2-alkyl-4,6-dihetero(N,O)alkyl-1,3,5-triazines toward selected tumor cell lines have been evaluated, and for the first time, the potential of 2-alkyl-4,6-dialkoxy-1,3,5-triazines has been shown.     

Synthesis and antiviral activity of benzimidazolyl- and triazolyl-1,3,5-triazines

A novel series of 1,3,5-triazine analogs was successfully synthesized through conjugation with benzimidazole or 1,2,4-triazole derivatives via a methylenethio linker. The new analogs were in vitro evaluated against HSV-1 in Vero cells; among these analogs, two compounds exhibited good effect in inhibiting HSV-1 replication (for compound 5p: EC₅₀ = 3.5 μg/ml, SI = 358; for compound 5r: EC₅₀ = 5.0 μg/ml, SI = 300) in comparison to acyclovir.     

Synthesis and antifungal activity of 3,3'-ethylenebis(5-alkyl-1,3,5-thiadiazine-2-thiones).

In a search for promising antifungal compounds, nine new 3,3'-ethylenebis(5-alkyl-1,3,5-thiadiazine-2-thiones) were synthesized by the reaction of ethylene diamine, carbon disulfide, formaldehyde, and the appropriate alkyl amine. The title compounds were tested for their antifungal activity in vitro against pathogenic (Trichophyton rubrum and Candida albicans), phytopathogenic (Penicillum expansum, Trichoderma hazianum, and Fasarium oxysporum), and aflatoxin producing (Aspergillus flavus) fungi. These compounds exhibited varied inhibitory effects on growth or sporulation of some tested fungal species.     

Synthesis and anti-inflammatory activity of 5-acyl-1,3,5-dithiazinanes

A series of 5-acyl-1,3,5-dithiazinanes were synthesized by multicomponent heterocyclization of amides with formaldehyde (CH₂O) and hydrogen sulfide (H₂S) in the presence of BuONa. Among the synthesized compounds, 5-trifluoroacetyl-1,3,5-dithiazinane and 5-acetylsalicyloyl-1,3,5-dithiazinane exhibited anti-inflammatory activity comparable with that of aspirin.     

Synthesis and anti-inflammatory activity of 2,3-dimethoxy- and 2,3,4-trimethoxy-substituted 3-dimethylaminopropionylbenzene

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 27, No. 7, pp. 36–37, July, 1993.     

Synthesis and anti-inflammatory activity of 1-alkyl-2-[3-dimethylaminopropionyl]-4,5-dimethoxybenzenes

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 28, No. 1, pp. 25–26, January, 1994.     

The effect of some anti-inflammatory agents on elastase release from neutrophils in-vitro

In view of the potential role of released polymorphonuclear leucocyte elastase in causing tissue damage, the effect of commonly used anti-inflammatory drugs on elastase release from neutrophils has been studied in-vitro. Elastase release from neutrophils exposed to the synthetic bacterial cell wall peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (10(-6) M) was quantitated using a radiometric immunoassay and a functional assay of elastase. Prednisolone and non-steroidal anti-inflammatory drugs inhibited elastase release at concentrations from 0.1 mM-0.1 nM. No inhibition by sulphosalicylic acid, D-penicillamine or chloroquine sulphate was observed. The clinical relevance of these findings is discussed.     

Synthesis and antimicrobial activity of some new 1-alkyl-2-alkylthio-1,2,4-triazolobenzimidazole derivatives

Some new derivatives of 1,2,4-triazolo[2,3-a]benzimidazoles were synthesized through the reaction of 1,2-diaminobenzimidazole with carbon disulfide. The resulting 1,2,4-triazolo-[2,3-a]benzimidazole-2-thione intermediate was reacted with one equivalent of alkyl halides to give the corresponding 2-alkylthio derivatives, which were further alkylated through the reaction with another one equivalent of different alkyl halides to afford the target compounds; 1-alkyl-2-alkylthio-1,2,4-traizolo[2,3-a]benzimidazoles. On the other hand, the 1,2-disubstituted derivatives with two identical alkyl substituents were prepared by the reaction of 1,2,4-triazolo[2,3-a]benzimidazole-2-thione with two equivalents of the alkyl halides. The structures of the new compounds were assigned by spectral and elemental methods of analyses. The synthesized compounds were tested for their antibacterial and antifungal activities. Most of the tested compounds proved comparable results with those of ampicillin and fluconazole reference drugs. The study indicated that, the antibacterial as well as the antifungal activities of the test compounds were improved with increase in the bulkiness of the introduced alkyl groups. Also, some active antibacterial compounds were tested for their antimycobacterial activity. All the test compounds showed equipotent antitubercular activity as that of INH as a reference drug.     

Antimalarial activity of 2-(substituted amino)-4,6-bis(trichloromethyl)-1,3,5-triazines and N-(chlorophenyl)-N'-[4-(substituted amino)-6-(trichloromethyl)-1,3,5-triazin-2-yl]guanidines

A series of 2-[[(dialkylamino)alkyl]amino]-4,6-bis(trichloromethyl)-1,3,5-triazines (III) and N-(4-chlorophenyl)-N'-[4-[[(dialkylamino)alkyl]amino]-6- (trichloromethyl)-1,3,5-triazin-2-yl]guanidines (IV) were prepared from 2,4,6-tris(trichloromethyl)-1,3,5-triazine and 2-chloro-4,6-bis(trichloromethyl)-1,3,5-triazine. Compounds of type III showed modest antimalarial activity while XIa with the camoquin side chain was more potent. Analogues of type IV broadly exhibited modest antimalarial activity.     

Evaluation of the anti-inflammatory activity of some pyrrolo[2,3-d]pyrimidine derivatives

A series of novel pyrrolo[2,3-d]pyrimidine and fused pyrrolo[2,3-d]pyrimidine derivatives were synthesized and their structures were characterized by elemental analysis, ¹H NMR, IR, and mass spectroscopy. Their in vivo anti-inflammatory activities were evaluated, and the results indicated that some of the title compounds compounds showed significant activities. These compounds are 2b ((7-(4-Methoxyphenyl)-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-hydrazine), 7b (4-(2-(Benzyl)hydrazinyl)-7-(4-methoxyphenyl)-5,6-diphenyl-7H-pyrrolo[2,3-d] pyrimidine), 7d (4-(2-(Benzyl)hydrazinyl)-7-(4-methoxyphenyl)-5-phenyl-7H-pyrrolo[2,3-d]pyrimidine), and 9b (4-(3,5-Dimethyl-4H-pyrazol-1-yl)-7-(4-Methoxyphenyl)-5,6-diphenyl-4,7dihydro-3H-pyrrolo[2,3-d]pyrimidine).     

Convenient synthesis of fused heterocyclic 1,3,5-triazines from some N-acyl imidates and heterocyclic amines as anticancer and antioxidant agents

N-Acyl imidates (2), reacting with 5-amino pyrazole (3), 2-aminobenzimidazole (4), 3-amino-1,2,4-triazole (5), 3,5-diamino-1,2,4-triazole (6), and 5-aminotetrazole (7) give pyrazolo[1,5-a][1,3,5]triazine (8), benzo[4,5]imidazo[1,2-a][1,3,5]triazine (9), [1,2,4]triazolo [2,3-a][1,3,5]triazine (10), [1,2,4]tri azolo[2,3-a][1,3,5]triazin-5-ylamine (12), and tetrazolo-[1,5-a][1,3,5]triazine (14) derivatives, respectively. The synthesized compounds were characterized on the basis of IR, (1)H-NMR, (13)C-NMR, and mass spectral data and elemental analyses results. Five of the newly synthesized compounds, 8a, 9a, 10a, 12a, and 14a, were selected by National Cancer Institute and screened for their anticancer activity against three cancer cell lines MCF7, NCI-H460, and SF-268, where 12a exhibited moderate anti-proliferation potential. 12a was, thus, further tested for anticancer activity against 60 human cancer cell lines and showed moderate growth inhibition potency. 12a showed a high growth inhibitory activity against A498 renal cancer cell line. All of the newly synthesized compounds 8-10, 12 and 14 were tested for their antioxidant capacity where they exhibited very high activity, even higher than the widely used reference antioxidants butylated hydroxytoluene and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). Compound 12a also showed the highest antioxidant activity.     

Synthesis and analgesic activity of some 4,6-disubstituted-3(2H)-pyridazinone derivatives

A series of 6-morpholino-4-aryl-3(2H)-pyridazinone alkanoic acids, their ester and amide derivatives were prepared and tested for their in vivo analgesic activity by using the p-benzoquinone-induced writhing test. The analgesic activity of the compounds 6-morpholino-4-aryl-3(2H)-pyridazinone (6a-b) were comparable but little lower than that of acetyl-salicylic acid (CAS 50-78-2) as an analgesic agent. The 6-morpholino-4-aryl-3(2H)-pyridazinones having a propanoic acid (10a-b), ester (7a) and amides (12a-b, 12d and 12g) as side chains at the position 2 of the pyridazinone ring showed higher activity than the reference compound without gastric ulceration forming potential. All other compounds generally showed higher activity but caused gastric ulceration in the animals.     

Synthesis and anti-inflammatory activity of some pyrazole derivatives

A novel series of pyrazoles containing benzenesulfonamides, 1,3,4-oxadiazole-2-thiones, 4-substituted-1,2,4-triazole-3-thiones, and 2-substituted-1,3,4-thiadiazoles has been synthesized. Anti-inflammatory activity of some synthesized compounds was evaluated in vivo utilizing a standard acute carrageenan-induced paw edema method. The most active anti-inflammatory agents 3, 8f, and 10f were evaluated for ulcerogenic liability in rats compared to indomethacin and celecoxib as reference standards. Molecular modeling studies were initiated herein to validate the attained pharmacological data and provide understandable evidence for the observed anti-inflammatory behavior.     

Synthesis and biochemical properties of substituted phenoxy- and anilino-1,3,5-triazines

Synthesis and Biochemical Properties of Substituted Phenoxy- and Anilino-1,3,5-triazines The nucleophilic substitution of one chlorine atom in 2,4-dichloro-6-diethylamino-1,3,5-triazine (1) by reaction with the hydroxyacetophenones 2a–c leads to the 2-acetylphenoxy-4-chloro-6-diethylamino-1,3,5-triazines 3a–c. Analogously, reaction of 1 with 4-fluoroaniline (4a) yields the monoanilino derivative 5a. However, under the same conditions, the dianilino derivative 5b is formed from 1 and 2-fluoroaniline (4b). Compounds of type 3 exhibit activity against fungi and protozoa, while 5 has herbicidal activity.