Ahmed A. Fadda

Synthesis, antitumor evaluation, molecular modeling and quantitative structure-activity relationship (QSAR) of some novel arylazopyrazolodiazine and triazine analogs.

The synthesis, in vivo and in vitro antitumor evaluation, and QSAR studies of some novel pyrazole analogs against Ehrlich Ascites Carcinoma (EAC) cells were described. In vitro results revealed that compounds 10, 6 and 4 were the most potent analogs against EAC, respectively. Moreover, in vivo evaluation of compounds 6 and 10 proved their capability to normalize the blood picture in comparison to 5-FU, a well known anticancer drug. These novel pyrazole analogs were molecularly designed with the goal of having significant potent cytotoxic effect against EAC cells. To develop a QSAR model capable of identifying the key molecular descriptors associated with the biological activity of the novel pyrazole analogs and predicting the cytotoxic effect for other novel pyrazole analogs against EAC cells, different QSAR models, using different physicochemical and topological molecular descriptors, were developed. Different molecular descriptors were predicted solely from the chemical structures of 16 pyrazolo-diazine and triazine analogs following the prediction of the equilibrium molecular geometry of each analog at the DFT level using B88-LYP functional energy and double zeta valence polarized (DZVP) basis set. It was found that dipole moment, excitation energy, the energy value of LUMO, solvent accessible surface area, and heat of formation were the key molecular descriptors in descriping the cytotoxic effect of those compounds against EAC.

Synthesis of some new thiazole derivatives of pharmaceutical interest

Condensation of 1,3-thiazolidinone derivatives 1a-c with different aromatic aldehydes and/or aryldiazonium chlorides gave the corresponding arylidenes 2-10 and arylazo-1,3-thiazolidinones 12-20. Bromination of 12 resulted in the formation of dibromo derivative 21. Treatment of 1a-c with HCHO-piperidine gave the Mannich adduct 24. Compound 1a was hydroxymethylated, oxidized and formylated to yield the products 25-28. The structures of the new products were confirmed by spectral and analytical methods.

Synthesis and molluscicidal activity of some new thiophene, thiadiazole and pyrazole derivatives

The base-catalyzed reaction of benzoyl acetone 1 with phenyl isothiocyanate yields the non-isolable intermediate 2. Treatment of 2 with dilute HCl afforded the corresponding thiocarbamoyl derivative 3. Reaction of the intermediate 2 with phenacyl bromide, ethyl bromoacetate, chloroacetonitrile, chloroacetyl chloride, bromodiethyl malonate and chloroacetone afforded the corresponding thiophene derivatives 5, 8, 15 and 17. The thiocarbamoyl derivative 3 reacts with arylazophenacyl bromide and/or hydrazine hydrate to afford the corresponding thiadiazole and pyrazole derivatives 20a-c and 22, respectively. These new synthesized compounds show generally a moderate molluscicidal activity to Biomphalaria alexandrina snails.

Synthesis and evaluation of curcumin analogues as cytotoxic agents.

Seventeen curcumin analogues were prepared and evaluated for in vitro and in vivo cytotoxicity against an Ehrlich ascites carcinoma (EAC). In vitro results revealed that compounds 10, 7, and 12 were the most potent analogues against EAC respectively. However, in vivo evaluation of compound 10 proved its capability to normalize the blood picture compared with 5-fluorouracil, a well-known anticancer drug.

Synthesis and antimicrobial activity of some novel hydrazide, benzochromenone, dihydropyridine, pyrrole, thiazole and thiophene derivatives.

As a part of ongoing studies in developing new potent antimicrobial agents, a novel synthesis of 2-cyano-N-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)acetohydrazide (3) has been reported. The latter compound was reacted with different reagents to give new heterocyclic compounds. The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, (1)H NMR, (13)C NMR and mass spectral data. Representative compounds of the synthesized products were tested and evaluated as antimicrobial agents.

Synthesis and Reactions of Some New Thiobarbituric Acid Derivatives

A series of novel thiobarbituric acid derivatives 3a–c , 5, and 12 were synthesized via the reaction of 4-benzoyl-1-cyanoacetylthiosemicarbazide ( 1 ) or its derivatives 2a–c , 9 with malonic acid and acetyl chloride. Coupling of thiobarbituric acid derivatives 3a-c and 5 with aromatic diazonium chlorides furnished a new series of the corresponding bisarylhydrazo-thiobarbituric dyes 4a–c . The reaction of 5 with cyclohexanone and sulfur under Gewald reaction condition afforded thieno[2,3-d]pyrimidine derivative 21 , that condensed with p-anisladehyde to give 5-arylidene thiobarbituric acid derivative 22 . The reaction of 1 with phenyl isothiocyanate afforded the non-isolable adduct 23 which was used as a key intermediate for the synthesis of polyfunctionally substituted thiazolidinone and thiobarbituric ring systems.

Utility of isothiocyanates in heterocyclic synthesis

Reaction of substituted pyrazolin-5-one and 3-phenyl-5-isoxazolone 1a-c with phenyl isothiocyanate in basic DMF gave the non-isolable sodium salt of the adduct 2a-c which was treated with HCl to give the corresponding thiocarbamoyl derivatives 3a-c . The latter compounds underwent heterocyclization upon treatment with chloroacetyl chloride and ethyl bromoacetate to give the corresponding thiazolidinone derivatives 6 and 7 . Compound 3a,b was oxidized to yield benzothiazoly pyrazolinone derivatives 8a,b . Also, nucleophilic substitution of 2 and 3 and with different nucleophilic reagents afforded the products 9-14 . Cyclocondensation of the thiocarbamoyl salt with some halogenated esters or acid chloride derivatives such as f -bromopropionate, ethyl chloroformate and f -bromo diethyl malonate afforded cyclized polyfunctionally thiazinone, thiazetidinone and thiazolidinone derivatives respectively 15-17 . The structures of the products were confirmed by spectral and micro analytical data.

Synthesis and Antioxidant and Antitumor Activity of Novel Pyridine, Chromene, Thiophene and Thiazole Derivatives

2‐Tosylacetonitrile (1) when reacted with α,β‐unsaturated nitriles 2a–c or a mixture of formaldehyde and 3‐amino‐2‐substituted‐pent‐2‐endinitriles 6a,b yielded pyridine derivatives 3a–c and 9a,b, respectively, while when subjected to react with salicylaldehyde yielded chromene derivatives 4 and 5, subsequently. The behavior of thiocarbamoyl derivative 10 derived from 1 towards some α‐halogenated compounds have been investigated as well as its behavior towards elemental sulfur and phenyl isothiocyanate. Newly synthesized compounds were screened for their antioxidant activity, erythrocytes haemolysis and bleomycin‐independent DNA damage. Some of the tested compounds exhibited promising activities.

Synthesis of some quaternary ammonium gemini surfactants and evaluation of their performance as corrosion inhibitors for carbon steel in oil well formation water containing sulfide ions

Three quaternary ammonium gemini surfactants were synthesized, characterized, and evaluated as corrosion inhibitors for carbon steel in oil well formation water containing sulfide ions. The corrosion inhibition efficiency was measured by using electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization techniques. The data obtained from EIS were analyzed to model the corrosion inhibition process through an equivalent circuit. The Tafel polarization results indicate that the inhibitors act as mixed type inhibitors. The nature of the protective film formed on the carbon steel surface was studied using scanning electron microscopy (SEM) and energy dispersive analysis of X-rays (EDX). The effect of molecular structure on the inhibition efficiency was investigated by quantum chemical calculations. It was found that the inhibition efficiency increased with increasing length of the alkyl group attached to the tertiary nitrogen atom. The values of standard adsorption equilibrium constant and free energy of adsorption for the three inhibitors were calculated and discussed. The adsorption of the inhibitor molecules on carbon steel surface was found to follow the Langmuir adsorption isotherm.

Chemistry of Enaminonitriles of Pyrano[2,3-c]pyrazole and Related Compounds

Abstract This review highlights the methods used for the synthesis of enaminonitriles of pyrano[2,3-c]pyrazole compounds. Their reactivity and synthetic importance were investigated. In this context, recent progress in the synthesis and use of enaminonitriles of pyrano[2,3-c]pyrazole as precursors for heterocyclic compounds is reviewed. The synthetic routes for preparation of enaminonitriles are based on multicomponent reactions including three- or four-component reactions. Enaminonitriles can be used as building blocks for carbocyclic five-, six-, and seven-membered heterocycles as well as fused heterocyclic compounds. The bibliography includes 94 references. GRAPHICAL ABSTRACT