Ibrahim M. Abdou

Synthesis and antitumor activity of 5-trifluoromethyl-2,4- dihydropyrazol-3-one nucleosides.

2,4-Dihydropyrazole glucosides 3a-3c were prepared and tested for their antitumor activity. The structures of these compounds were established by (1)H and (13)C-NMR spectroscopy. Glucoside 3b shows an in vitro IC(50) value of 16.4 muM against proliferation of the human promyelotic leukemia (HL60) cell line.

A Facile Synthesis of 6-Aryl-5-cyano-1-(β-d-pyranosyl or β-d-furanosyl)-2-thiocytosines

Abstract The treatment of a piperidinium salt of 6-aryl-5-cyano-2-thiouracil with an O-peracetyl-α- d -pyranosyl bromide produces a mixture of N1-(β- d -pyranosyl)-2-thiouracil and its N1,S2-disubstituted analog. By contrast, the reaction of a silyl derivative of the 2-thiouracil with an O-peracetyl-β- d -pyranose furnishes the mononucleoside selectively. Both the mononucleoside/dinucleoside mixture and pure mononucleoside undergo ammonolysis under mild conditions to give the β- d -nucleoside of 6-aryl-5-cyano-2-thiocytosine. The silyl method also provides an easy access to β- d -ribosyl nucleosides.

Synthesis and Evaluation of Antimicrobial Activity of Some Pyrimidine Glycosides

Reaction of ethyl 4-thioxo-3,4-dihydropyrimidine-5-carboxylate derivatives 1a,b and ethyl 4-oxo-3,4-dihydropyrimidine-5-carboxylate 1c with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide in KOH or TEA afforded ethyl 2-aryl-4-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosylthio or/ oxy)-6-methylpyrimidine-5-carboxylate 6a-c. The glucosides 6a and 6b were obtained by the reaction of 1a and 1b with peracetylated glucose3 under MW irradiation. Mercuration of 1a followed by reaction with acetobromoglucose gave the same product 6a. The reaction of 1a-c with peracetylated ribose 4 under MW irradiation gave ethyl 2-aryl-4-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosylthio)-6-methylpyrimidine-5-carboxylate 8a–c. The deprotection of 6a–c and 8a–c in the presence of methanol and TEA/H2O afforded the deprotected products 7a–c and 9a–c. The structure were confirmed by using 1H and 13CNMR spectra. Selected members of these compounds were screened for antimicrobial activity.

The first direct ammonolysis of 2-thiouracil nucleosides to 2-thiocytosine nucleosides

Sugar-peracetylated 1-(β-d-glucopyranosyl)-, 1-(β-d-galactopyranosyl)-, and 1-(β-d-xylopyranosyl)-6-aryl-5-cyano-2-thiouracils 2–4 and the corresponding 1-pyranosyl-2-(pyranosylthio)pyrimidines 5–7 undergo efficient ammonolysis (NH3/MeOH, 0→23°C, 16 h) to give the corresponding 1-(β-d-pyranosyl)-6-aryl-5-cyano-2-thiocytosines.

4-(3-furyl)-2-(4-methylpiperazino)pyrimidines: Potent 5-HT2A receptor antagonists

Abstract The title pyrimidines 7–12 are potent 5-HT2A receptor ligands with fairly strong behavioral antagonistic activity. A comparison of the structural and binding properties within the entire group of these and other pyrimidines demonstrates two different modes of the bioactive complex formation.

Synthesis of quinazolines and quinazolinones via palladium-mediated approach

Abstract Quinazoline derivatives have drawn attention in the field of heterocyclic chemistry because of their unique skeleton and interesting biological applications. This review summarizes the recent palladium-catalyzed reactions used to construct quinazoline and its related 4(3H)-quinazolinone analogues. The mechanisms of some Pd-catalyzed reactions are also discussed.

Glucopyranosides derived from 6-aryl-5-cyano-2-(methylthio)pyrimidin-4(3H)ones.

ABSTRACT The reaction of 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide with a 6-aryl-5-cyano-2-(methylthio)pyrimidin-4(3H)one in aqueous acetone in the presence of KOH furnishes a 4-(β-D-glucopyranosyloxy)pyrimidine and a 3-(β-D-glucopyranosyl)pyrimidine as the major and minor product, respectively.

Microwave-Assisted Synthesis of 2(1H)-Pyridones and Their Glucosides as Cell Proliferation Inhibitors

A new series of substituted 2(1H)-pyridones (4a–i) and their glucosides (5, 6a–e) were prepared as potential agents against leukemia (HL-60) cells. Glucosides (5,6a–e) were synthesized using three independent methods. Microwave protocol as an ecologically new method was used to synthesize the target compounds. Structures of the new products were confirmed using one- and two-dimensional NMR spectroscopy. In vitro exposure of pyridones substituted at position 4 with a 2-thienyl or 2-(trifluoromethyl)phenyl were found to exhibit high antiproliferation activities; in particular, 3-cyano-4-(thien-2′-yl)-6-(4″-chlorophenyl)-2(1H)-pyridone (4c) and its glucoside analogue (6c) had the highest activity.

Cytotoxic activity of the novel heterocyclic compound G-11 is primarily mediated through intrinsic apoptotic pathway

Natural and chemically synthesized heterocyclic compounds have been explored for their potential use as anticancer agents. We had synthesized non-natural heterocyclic analogs and evaluated their anti-tumor activity by measuring effect on cell proliferation and induction of apoptosis in different cell lines. Previously, we identified a pyrazole-containing compound (G-11) showing cytotoxic effect towards leukemia and lymphoma cell lines. In this study, we further investigated the mechanistic aspects of anticancer properties of G-11 in HL-60 cell line. We demonstrated that cytotoxic effect of G-11 is mediated by caspase-dependent apoptosis. However, the involvement of mitochondrial dysfunction induced by G-11 was independent of caspases. G-11 triggered generation of ROS, caused disruption of mitochondrial transmembrane potential, increased release of cytochrome c to the cytosol, and altered the expression of Bcl-2 and Bax proteins. These results suggest significant involvement of intrinsic apoptotic pathway. This study comprehensively details the possible mechanisms of action of a novel heterocyclic compound which could find its potential use as an anticancer agent.

Antimicrobial Evaluation of New Synthesized Pyridine Nucleosides Under Solvent-Free Conditions

Two series of novel 3-cyano-2-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxo) pyridines and 3-cyano-2-(2,3,5-tri-O-acetyl-β-D-ribofuranosyloxy)-4-trifluromethyl-6-phenyl pyridine were synthesized using efficient microwave methods. The targeted compounds were obtained in high yields by reacting 2-(1H)-pyridone or its salt with activated sugars using SiO2 under solvent-free conditions. Ammonolysis of the resulted acetylated nucleosides produced 3-cyano-2-(β-D-glucopyranosyloxo)-pyridines and 3-cyano-2-(β-D-ribofuranosyloxy)-4-trifluoromethyl-6-phenyl pyridine. These new products were fully characterized using 1D and 2D NMR. These compounds were screened for their antibacterial activities against G+ and G– bacteria and some found to exhibit better antibacterial activities than the control drug.