Hosam A. Saad

Microwave Assisted Synthesis of Some New Fused 1,2,4-Triazines Bearing Thiophene Moieties With Expected Pharmacological Activity

Rapid and efficient solvent-free synthesis of 4-amino-3-mercapto-6-[2-(2-thienyl)vinyl]-1,2,4-triazin-5(4H)-one 1 under microwave irradiation is described. Some new fused heterobicyclic nitrogen systems such as 1,2,4-triazino[3,4-b][1,3,4]thiadiazinones, 1,3,4-thiadiazolo[2,3-c][1,2,4]triazinone and pyrazolo[5,1-c]-[1,2,4]triazine-7-carbonitrile, have been synthesized by treatment of 1 with bifunctional oxygen and halogen compounds, CS2/KOH and malononitrile via heterocyclization reactions, in addition to some uncondensed triazines. Structures of the products have been deduced from their elemental analysis and spectral data (IR, 1H-NMR, 13C-NMR). Select new synthesized compounds were screened as anticancer agents, with some showing activity as cytotoxic agents against different cancer cell lines.

Synthesis and Analgesic Activity of Some New Pyrazoles and Triazoles Bearing a 6,8-Dibromo-2-methylquinazoline Moiety

2-(6,8-Dibromo-2-methylquinazolin-4-yloxy)-acetohydrazide (4) was prepared by the reaction of 6,8-dibromo-2-methylbenzo-[d][1,3]oxazin-4-one with formamide to afford quinazolinone 2, followed by alkylation with ethyl chloroacetate to give the ester 3. Treatment of ester 3 with hydrazine hydrate and benzaldehyde afforded 4 and styryl quinazoline 5. The hydrazide was reacted with triethyl orthoformate, acetylacetone and ethyl acetoacetate and benzaldehyde derivatives to afford the corresponding pyrazoles 6, 7, 9 and hydrazone derivatives 10a-c. Cyclization of hydrazones 10a-c with thioglycolic acid afforded the thiazole derivatives 11a-c. Reaction of the hydrazide with isothiocyanate derivatives afforded hydrazinecarbothioamide derivatives 12a-c, which cyclized to triazole-3-thiols and thiadiazoles 13a-c and 14a-c, respectively. Fusion of the hydrazide with phthalimide afforded the annelated compound 1,2,4-triazolo[3,4-a]isoindol-5-one (15). The newly synthesized compounds were characterized by their spectral (IR, 1H-, 13C-NMR) data. Selected compounds were screened for analgesic activity.

Synthesis of Some New Pyrimidine Derivatives of Expected Antimicrobial Activity

2-(2-Arylvinyl)-6-methyl-4-mercapto-5-acetylpyrimidine derivatives 3 a − d , were synthesized form the reaction of the appropriate isothiocyanate derivatives 1 with α, β -unsaturated aminoketone 2 . Compound 3 was alkylated with methyl iodide, ethyl chloroacetate and/or bromosugar to afford 6 , 9 , and 22 a − c respectively. Cyanoethylation of 3 b afforded 6 b which upon cyclization with hydrazine hydrate gave pyrazolopyrimidine 7 . Bromination of 6 b gave dibromo compound 8 . Thieno[2,3-d]pyrimidines 10 and 12 were obtained by ring closure of the alkylated product 9 with TEA/EtOH and/or through cyclization of the hydrazide 11 with NaOEt/EtOH. While, Thieno[2,3-d]pyrimidine 14 was obtained directly by alkylation of 3 b with chloroacetone in both TEA/EtOH and Na2CO3 solution. The cycloaddition products 15 and 16 were obtained by reaction of 3b with diethylmaleate and/or maleic anhydride. Formation of 1,3,4-oxadiazole 17 , pyrazoles 18 and 19 where obtained by treating the hydrazide 11 with carbon disulphide, triethyl orthoformate and acetylacetone respectively. While, reaction of 11 with p-chlorobenzaldehyde resulted in the Schiffs base 20 which, cyclizes with thioglycolic acid to afford thiazolidone 21 . Hydrolysis of 22 a − c in TEA/MeOH afforded the free sugar 23 a − c . The structures of all the new compounds were confirmed using IR, 1 H, and 13 C NMR spectra and microanalysis. Selected members of the synthesized compound were screened for antimicrobial activity.

Synthesis and anticancer activity of some new s-glycosyl and s-alkyl 1,2,4-triazinone derivatives.

A series of S-glycosyl and S-alkyl derivatives of 4-amino-3-mercapto-6-(2-(2-thienyl)vinyl)-1,2,4-triazin-5(4H)-one (1)were synthesized using different halo compounds such as preacetylated sugar bromide, 4-bromobutylacetate, 2-acetoxyethoxy-methyl bromide, 3-chloropropanol, 1,3-dichloro-2-propanol, epichlorohydrin, allyl bromide, propargyl bromide, phthalic and succinic acids in POCl3. The structures of the synthesized compounds have been deduced from their elemental analysis and spectral (IR, 1H-NMR, and 13C-NMR) data. Some of the synthesized compounds were screened as anticancer agents. Significant anticancer activities were observed in vitro for some members of the series, and compounds 4-Amino-3-(3-hydroxypropylthio)-6-(2-(2-thienyl)vinyl)-1,2,4-triazin-5(4H)-one (12) and 3-(4-Oxo-3-(2-(2-thienyl)vinyl)-4H-[1,3,4]thiadiazolo-[2,3-c][1,2,4]tr-iazin-7-yl)propanoic acid (18) are active cytotoxic agents against different cancer cell lines.

Spectral, thermal and kinetic studies of charge-transfer complexes formed between the highly effective antibiotic drug metronidazole and two types of acceptors: σ- and π-acceptors.

Understanding the interaction between drugs and small inorganic or organic molecules is critical in being able to interpret the drug-receptor interactions and acting mechanism of these drugs. A combined solution and solid state study was performed to describe the complexation chemistry of drug metronidazole (MZ) which has a broad-spectrum antibacterial activity with two types of acceptors. The acceptors include, σ-acceptor (i.e., iodine) and π-acceptors (i.e., dichlorodicyanobenzoquinone (DDQ), chloranil (CHL) and picric acid (PA)). The molecular structure, spectroscopic characteristics, the binding modes as well as the thermal stability were deduced from IR, UV-vis, (1)H NMR and thermal studies. The binding ratio of complexation (MZ: acceptor) was determined to be 1:2 for the iodine acceptor and 1:1 for the DDQ, CHL or PA acceptor, according to the CHN elemental analyses and spectrophotometric titrations. It has been found that the complexation with CHL and PA acceptors increases the values of enthalpy and entropy, while the complexation with DDQ and iodine acceptors decreases the values of these parameters compared with the free MZ donor.

Utility of positron annihilation lifetime technique for the assessment of spectroscopic data of some charge-transfer complexes derived from N-(1-Naphthyl)ethylenediamine dihydrochloride

In this work, structural, thermal, morphological, pharmacological screening and positron annihilation lifetime measurements were performed on the interactions between a N-(1-Naphthyl)ethylenediamine dihydrochloride (NEDA·2HCl) donor and three types of acceptors to characterize these CT complexes. The three types of acceptors include π-acceptors (quinol and picric acid), σ-acceptors (iodine) and vacant orbital acceptors (tin(IV) tetrachloride and zinc chloride). The positron annihilation lifetime parameters were found to be dependent on the structure, electronic configuration, the power of acceptors and molecular weight of the CT complexes. The positron annihilation lifetime spectroscopy can be used as a probe for the formation of charge-transfer (CT) complexes.

Click reaction based synthesis, antimicrobial, and cytotoxic activities of new 1,2,3-triazoles ☆

Three-motif pharmacophoric models 20a-e and 21-25 were prepared in good yields by CuAAC of two azido substrates 2 and 11 with seven terminal acetylenic derivatives including chalcones 17a-e, theophylline 18 and cholesterol 19. The structure of these compounds was elucidated by NMR, MS, IR spectroscopy and micro analyses. This series was screened as antimicrobial and cytotoxic agents in vitro. Most derivatives showed appreciable antibacterial activity, but they displayed weak cytotoxic, and antifungal activities. Notably, conjugate 25 (cream of the crop) was found to be more active than Ampicillin against Escherichia coli and Staphylococcus aureus and showed appreciable antifungal and cytotoxic activities as well.

Novel charge-transfer complexes of 4-hexylamino-1,8-naphthalimide-labelled PAMAM dendrimer with some acceptors: a spectrophotometric study

Poly(amidoamine) dendrimers are very interesting macromolecules with highly branched structures and globular-shaped branched polymeric architectures. They are widely used for drug and gene delivery applications. In order to provide important insight into the interactions of poly(amidoamine) dendrimers with some organic acceptors, the binding of small molecules to 4-hexylamino-1,8-naphthalimide-labelled PAMAM dendrimer (PD) have been studied by spectrophotomeric method. The acceptors used in this research include chloranilic acid (CLA), p-chloranil (CHL), 2,6-dichloroquinone-4-chloroimide (DCQ), 2,6-dibromoquinone-4-chloroimide (DBQ), 7,7ʹ,8,8ʹ-tetracyanoquinodimethane (TCNQ), picric acid (PA), 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and iodine monobromide (IBr). The spectrophotometric measurements proved that all the charge-transfer (CT) complexes are formed via a stoichiometry (PD: acceptor) of 1:2 (except for IBr acceptor). Accordingly the obtained complexes could be formulated as [(PD)(CLA)2], [(PD)(DCQ)2], [(PD)(DBQ)2], [(PD)(TCNQ)2], [(PD)(PA)2], [(PD)(CHL)2], [(PD)(DDQ)2] and [(PD)(IBr)4]. Benesi–Hildebrand and its modification methods were applied to estimate the spectroscopic and physical data.

Infrared, Raman, 1H NMR, TG, and SEM properties of the charge-transfer interactions between tris(hydroxymethyl)methane with the acceptors picric acid, chloranilic acid, and 1,3-dinitrobenzene

Intermolecular charge-transfer complexes (CT) between the tris(hydroxymethyl)methane (THM) as a donor and picric acid (PA), chloranilic acid (CLA) and 1,3-dinitrobenzene (DNB) as a π-acceptor have been structurally, thermally and morphologically studied in methanol at room temperature. Based on elemental analyses (CHN), the stoichiometry of the obtained CT complexes (THM: acceptor molar ratios) was determined to be 1 : 1 for all three complexes. The CT complexes have been characterized via elemental analyses (CHN), IR, Raman and 1H NMR spectroscopy in order to predict the position of the CT interaction between the donating and accepting sites. Thermal decomposition behavior of these complexes was also investigated, and their kinetic thermodynamic parameters were calculated with Coats-Redfern and Horowitz-Metzger methods. Finally, the microstructure properties of these complexes were observed using scanning electron microscope (SEM).

Intermolecular hydrogen bond complexes by in situ charge transfer complexation of o-tolidine with picric and chloranilic acids

A two new charge transfer complexes formed from the interactions between o-tolidine (o-TOL) and picric (PA) or chloranilic (CA) acids, with the compositions, [(o-TOL)(PA)(2)] and [(o-TOL)(CA)(2)] have been prepared. The (13)C NMR, (1)H NMR, (1)H-Cosy, and IR show that the charge-transfer chelation occurs via the formation of chain structures O-H⋯N intermolecular hydrogen bond between 2NH(2) groups of o-TOL molecule and OH group in each PA or CA units. Photometric titration measurements concerning the two reactions in methanol were performed and the measurements show that the donor-acceptor molar ratio was found to be 1:2 using the modified Benesi-Hildebrand equation. The spectroscopic data were discussed in terms of formation constant, molar extinction coefficient, oscillator strength, dipole moment, standard free energy, and ionization potential. Thermal behavior of both charge transfer complexes showed that the complexes were more stable than their parents. The thermodynamic parameters were estimated from the differential thermogravimetric curves. The results indicated that the formation of molecular charge transfer complexes is spontaneous and endothermic.