Design, synthesis and evaluation of novel benzimidazoles, benzothiazoles and benzofurans incorporating pyrazole moiety as antiangiogenic agents.

Novel benzimidazoles, benzothiazoles and benzofurans incorporating pyrazole moiety have been synthesized and screened for their antiangogenic activities, by testing their ability to inhibit human umbilical vein endothelial cell (HUVEC) proliferation, cord formation and migration in response to chemoattractant. 3 compounds 19, 23 and 26 showed antiangiogenic activities at non-cytotoxic concentrations. Compound 19 was the most active with chemotaxis activity data nearly comparable to that of the positive control, TNP-470. Compound 42 showed a significant cytotoxic effect on the tested cancer cell lines and less antiangiogenesis activity compared to compounds 19, 23 and 26. All the tested compounds, in contrary to TNP-470, interfered with the migratory function of HUVECs in response to vascular endothelial growth factor rather than the endothelial cells proliferation or cord formation. Moreover, a docked pose of compounds 19 and 26 was obtained bound to kinase insert domain receptor using Molecular Operating Environment module.

Synthesis and biological investigations of some novel thiazolylbenzimidazoles, and benzimidazolyl-thiazolo[4,5-d]pyrimidines.

Several thiazolyl-benzimidazoles 2, 4a-c were synthesized through the reaction of 2-cyanomethyl-1 H-benzimidazole with isothiocyanates followed by cyclization of the produced intermediates 1a-b with either ethyl bormocetate or phenacyl bromides. When the cyclization was performed in alkaline medium, thiophenyl-benzimidazoles 5, 6a, b were produced. Another series of thiazolyl-benzimidazoles 8 a-d was obtained from 2,3-dihydrothiazole-2-(3 H)-thiones 7a-d and 2-cyanomethyl-1 H-benzimidazole, then cyclized to the corresponding thiazolo[4,5-d]pyrimidine 10a-d. Most of the prepared compounds were evaluated for their in-vitro antibacterial, antifungal, anti-HIV and anti-cancer activities. They showed promising antifungal activity.

Synthesis of novel thiazolo[4,5-d]pyrimidine derivatives for antimicrobial, anti-HIV and anticancer investigation.

Some novel thiazolo[4,5-d]pyrimidines containing 6-arylideneamino (3a-e). 2-dicyanomethylidene (5a), 2-(cyanoethoxy carbonyl) methylidene (5b) or 2-hydrazono (7a, b) moieties were synthesized. The prepared compounds were tested in vitro for their antibacterial, antifungal, anti-HIV and anticancer activities. Most of them showed promising antifungal activity, but only a few compounds exhibited anticancer activity.

Synthesis and biological investigations of some new thiazolylbenzimidazoles and benzimidazolylthiazolo[3,2-a]pyridines.

2-[(4-Oxo-4,5-dihydrothiazol-2-yl)methyl]-1H-benzimidazole (2) was prepared through the reaction of 2-cyanomethyl-1H-benzimidazole (1) with thioglycolic acid. The syntheses of its arylidene 3 and diazo-coupled compounds 5 and the cyclization of the aforementioned thiazolylbenzimidazole to benzimidazolylthiazolo[3,2-a]pyridines 8 were also performed. The prepared compounds were screened for their in-vitro antibacterial, antifungal, anti-HIV, and anticancer activities: they show promising antifungal activity.

Synthesis and biochemical evaluation of N-(1-substituted-cycloalkyl)-beta-(3,4-dimethoxy; or dihydroxy) phenethylamines: potential dopaminergic agents.

The design and synthesis of some hybrid-structures comprising the dopamine framework on one hand and an N-(1-substituted-cycloalkyl) moiety on the other have been elaborated. Selective members of the new series were biochemically assayed to determine their effects on the levels of dopamine and its metabolite norepinephrine in brains of Albino-rats. The brain MAO activity was also estimated. The results were compared with those displayed by apomorphine, metoclopramide and PCP.

Assessment of anti-HIV activity of some benzimidazolylthiazoles.

Benzimidazolylthiazoles 2 were synthesized by condensing 1H-benzimidazole-2-acetonitrile (1) with sulphur and isothiocyanates. The syntheses of the Schiff bases 3, thioureas 4, and thiazolopyrimido[1,6-a]benzimidazoles 5 and 6 are also described. Seven compounds were evaluated in vitro against human HIV, however, no significant activity was observed with any of these compounds.

Synthesis of alkyloxybenzamide derivatives as potential antimicrobial agents.

Three series of alkyloxybenzamido derivatives have been prepared. The first comprises N1-[4-(4-alkyloxybenzamido)benzoyl]-N2-substituted alkylidene hydrazine, the second involves 1-[4-(4-alkyloxybenzamido)benzoyl]-4-alkyl, aryl, or aralkyl-3-thiosemicarbazides, and the third includes 1-substituted-5-[4-(4-alkyloxybenzamido)phenyl]-1,3,4-triazole-2-t hione. Representative samples of the prepared compounds were tested for their in-vitro antimicrobial activity.

Novel benzimidazoles with potential antimicrobial and antineoplastic activities.

The synthesis of some substituted 4-[1-(1-(1H-benzimidazol-2-yl) alkylamino]-1,5-dihydro-2H-pyrrol-2-ones and 3-[1-(1H-benzimidazol-2-yl)alkyl]-2-substituted-4(3H)-quinazolinon es is described. Five compounds displayed in vitro antibacterial and antifungal activities. Three of these compounds were tested against P-388 lymphocytic leukemia in mice and were inactive.

Syntheses and in vitro antimicrobial evaluation of some benzimidazol-2-ylmethylthioureas, benzimidazol-2-ylacetylthiosemicarbazides and products of their condensation with monochloroacetic acid.

N-Benzimidazol-2-ylacetyl-N'-[alkyl- and arylthio (carbamoyl)]hydrazines and N-benzimidazol-2-ylmethyl-N'-alkyl- and -arylthioureas were subjected to condensation with monochloroacetic acid to afford N-benzimidazol-2-ylacetyl-N'-2,3, 4,5-tetrahydro-4-oxo-3-alkyl- and -arylthiazol-2-ylidenehydrazines and 3-benzimidazol-2-ylmethyl-2-alkyl- and arylimino-2,3-dihydrothiazol-4-(5H)ones, respectively. In preliminary antimicrobial testing, some compounds turned out to have significant activity against Staphylococcus aureus.

Syntheses and in vitro antimicrobial activities of thiazolo-[3,2-a]benzimidazol-3(2H)-ones.

Taking advantage of the nucleophilic reactivity of the 2-methylene carbon atom in thiazolo[3,2-a]-benzimidazol-3(2H)-one, a number of 2-isatinylidene and 2-arylazo derivatives have been prepared. The novel compounds were subjected to antimicrobial testing.

Synthesis of some 4-hydroxypiperazine and N.N.-dibenzylhydroxylamine esters with potential local anaesthetic activity.

In the synthetic approach to some new local anaesthetics, it was desirable to prepare esters of N1-methyl-N4-hydroxypiperazine and N.N-dibenzylhydroxylamine. Their local anaesthetic activity testing is in progress.

Synthesis of some alkoxybenzamide derivatives as smooth muscle relaxant agents.

The preparation of 16 new N-substituted p-aminobenzamide derivatives which contain diethylaminoethyl-N-methylpiperazine, piperidine and morpholine moieties were described. Preliminary pharmacological testing of representative compounds showed that some of the prepared compounds possess anticholinergic and antihistaminic activities.

Synthesis of benzimidazole derivatives with potential antispasmodic activity.

Some new esters and amides of benzimidazole-1-acetic acid which contain different cationic heads were prepared as atropine substitutes. Preliminary pharmacological testing showed that the prepared compounds possess atropine-like activity.