Hussein El-Kashef

1,3-Diphenylpyrazoles: synthesis and antiparasitic activities of azomethine derivatives

1,3-Diphenylpyrazole-4-carboxaldehyde and 1-(4-nitrophenyl)-3-phenylpyrazole-4-carboxaldehyde were obtained from the appropriated phenylhydrazones via the Vilsmeier-Haack reaction. These two aldehydes were functionalized by various substituted anilines or substituted benzylamines. Antiparasitic activities of the corresponding azomethines were assessed. In the most cases, nitrated compounds were found to be more efficient than non-nitrated ones against Plasmodium falciparum, Trichomonas vaginalis and Leishmania infantum.

Facile synthesis of some new pyrazolo[3,4-b] pyrazines and their antifungal activity

The synthesis of new pyrazolo[3,4-b]pyrazines and related heterocycles has been reported. The key intermediate 1,6-diphenyl-3-methyl-1H-pyrazolo[3,4-b]pyrazine-5-carbonitrile 2 was obtained in one pot synthesis from the reaction of 5-amino-3-methyl-4-nitroso-1-phenylpyrazole 1 with benzoylacetonitrile. Modest antifungal activity was shown for some of the prepared compounds.

Antiproliferative activity of some 1,4-dimethylcarbazoles on cells that express estrogen receptors: part I

Several 9H-carbazole derivatives are used for various pharmacological applications. Many of these compounds demonstrated cytotoxic and anticancer activities. In this work, we have investigated the cytotoxic activity of some substituted carbazoles against cancer cell lines (MCF-7, and ISK). The derivative 2a showed the highest inhibitory activity against both cell lines.

Synthesis and anticonvulsant activity of some new pyrazolo[3,4-b]pyrazines and related heterocycles.

A series of new pyrazolo[3,4-b]pyrazines containing, 1,2,4-oxadiazolyl, thiadiazolyl, imidazothiadiazolyl, thiazolidinonyl, substituents and other different substituents, was synthesized using 1,6-diphenyl-3-methyl-lH-pyrazolo[3,4-b]pyrazine-5-carbonitrile (2) as a starting material. Some of the newly prepared compounds were evaluated for their anticonvulsant activity. Compounds 9a, 13a-d and 14a at a dose of 10mg/kg showed very significant anticonvulsant activity and increased the latency time of PTZ-induced tonic seizures. Compound 9b showed significant effect.

LIQUID CRYSTALLINE POLYMERS. IV. THERMOTROPIC LIQUID CRYSTALLINE POLY(ARYLIDENE-ETHER)S AND COPOLYMERS CONTAINING N-METHYLPIPERIDONE LINKED TO THE MAIN CHAIN THROUGH SPACERS OF VARIOUS LENGTHS

Two novel series of poly(arylidene-ether)s and copoly(arylidene-ether)s were synthesized from N-methylpiperidone and/or cyclohexanone respectively. The first series (homopolymers) was derived from 4,4′-diformyl-α,ω-diphenoxyalkane or 4,4′-diformyl-2,2′ dimethoxy-α,ω-diphenoxyalkane with N-methylpiperidone. The second series (copolymers) was derived from the diphenoxyalkanes (I–VIII) with N-methylpiperidone and cyclohexanone. The inherent viscosities of the polymers thus prepared were in the range of 0.37–0.98 dI/g. The majority of the polymers and copolymers are soluble in chlorinated hydrocarbons. DSC measurements and microscope observation under polarized light demonstrate that this type of poly(arylidene-ether)s form nematic mesophase over a wide temperature range in contrast to the corresponding copoly(arylidene-ether)s. All of the polymers and copolymers exhibited thermotropic liquid crystalline properties. In most cases, the mesophase extends up to 315°C, where thermal decomposition prevents further observation. The morphology of polymer IXb and copolymer XIb as a selected example was examined by scanning electronic microscope.

Synthesis and anti-microbial activity of some imidazo[1', 2' :5,6]pyrimido[4,5-c]pyridazines and related heterocycles

The synthesis of the title heterocycles was achieved using 3-amino-5,6-diphenylpyridazine-4-carbonitrile (4) as a starting material. This compound was converted into the corresponding 4-imidazolinyl derivative 5 which was then subjected to cyclization reactions to afford the title compounds.

SYNTHESIS AND SOME REACTIONS OF PYRROLO[1″,2″:1′,6′]PYRAZINO-[2′, 3′: 4, 5]THIENO[2, 3-b]QUINOLINES; A NEW FUSED PYRAZINE RING SYSTEMS

Abstract Ethyl 3-amino-4-(4-chlorophenyl)-5, 6, 7, 8-tetrahydrothieno[2, 3-b]quinoline-2-carboxylate (1) was converted into the corresponding 3-(1-pyrrolyl) derivative 2. Various derivatives of 2 were prepared. The synthesis of the title compounds and other related heterocyclic systems are reported.

3-(Dipropylamino)-5-hydroxybenzofuro[2,3-f]quinazolin-1(2H)-one (DPA-HBFQ-1) plays an inhibitory role on breast cancer cell growth and progression.

A series of unknown 3-(alkyl(dialkyl)amino)benzofuro[2,3-f]quinazolin-1(2H)-ones 4-17 has been synthesized as new ellipticine analogs, in which the carbazole moiety and the pyridine ring were replaced by a dibenzofuran residue and a pyrimidine ring, respectively. The synthesis of these benzofuroquinazolinones 4-17 was performed in a simple one-pot reaction using 3-aminodibenzofuran or its 2-methoxy derivative, as starting materials. From 3-(dipropylamino)-5-methoxybenzofuro[2,3-f] quinazolin-1(2H)-one (13), we prepared 3-(dipropylamino)-5-hydroxybenzofuro[2,3-f]quinazolin-1(2H)-one (18), referred to as DPA-HBFQ-1. The cytotoxic activities of all the synthesized compounds, tested in different human breast cancer cell lines, revealed that DPA-HBFQ-1 was the most active compound. In particular, the latter was able to inhibit anchorage-dependent and -independent cell growth and to induce apoptosis in estrogen receptor alpha (ERα)-positive and -negative breast cancer cells. It did not affect proliferation and apoptotic responses in MCF-10A normal breast epithelial cells. The observed effects have been ascribed to an enhanced p21(Cip1/WAF1) expression in a p53-dependent manner of tumor suppressor and to a selective inhibition of human topoisomerase II. In addition, DPA-HBFQ-1 exerted growth inhibitory effects also in other cancer cell lines, even though with a lower cytotoxic activity. Our results indicate DPA-HBFQ-1 as a good candidate to be useful as cancer therapeutic agent, particularly for breast cancer.

SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF SOME NEW PYRAZOLES AND THIEN0[2,3-c]PYRAZOLES

Abstract Starting with 5-chloro-1,3-diphenyl- 1H-pyrazole-4-carboxaldehyde (1), both of (4-cyano-1,3-diphenyl-1H-pyrazol-5-ylthio) acethydrazide (6) and 1,3-diphenyl- 1H-thieno[2,3-c] pyrazole-5-carbohydrazide (15) were synthesized. These hydrazides (6 and 15) were used as key intermediates in the synthesis of other new pyrazoles 7–12 and thieno[2,3-c]pyrazoles 16–30 respectively. Some of the prepared compounds were screened in vitro for their antibacterial and antifungal activity.

Indenopyrazole oxime ethers: synthesis and β1-adrenergic blocking activity.

This paper reports the synthesis and cardiac activity of new β-blockers derived from (Z/E)-indeno[1,2-c]pyrazol-4(1H)-one oximes (5a,b). The latter compounds were allowed to react with epichlorohydrin, followed by reacting the oxiranyl derivatives formed (6a,b) with some aliphatic amines to give the target compounds (Z/E)-1-phenyl-1H-indeno[1,2-c]pyrazol-4-one O-((2-hydroxy-3-(substituted amino)propyl)oxime (7a-c) and (Z/E)-1-methyl-1H-indeno[1,2-c]pyrazol-4-one O-((2-hydroxy-3-(substituted amino)propyl)oxime (8a-c). These final products 7a-c and 8a-c were evaluated for their ability to modulate the cardiac performance of a prototype mammalian heart. The results showed that, out of these molecules tested, 7b elicits a more potent depressant effect on contractility and relaxation, and competitively antagonizes β1-adrenergic receptors.