Said A. El-Feky

Synthesis, molecular docking and anti-inflammatory screening of novel quinoline incorporated pyrazole derivatives using the Pfitzinger reaction II

In continuation of our study of novel quinolines with anti-inflammatory activity using the Pfitzinger reaction, several new quinoline derivatives were synthesized and tested for their anti-inflammatory and ulcerogenic effect. A docking study on the COX-2 binding pocket was carried out for the target compounds to rationalize the possible selectivity of them against COX-2 enzyme. The most active compounds (5a, 8a and 11a) were found to be superior to celecoxib. Compound 11a demonstrated the highest anti-inflammatory activity as well as the best binding profiles into the COX-2 binding site. Moreover, compounds 9c, 9e, 10a and 11a were devoid of ulcerogenic activity.

Synthesis and antimalarial bioassay of quinine - peptide conjugates.

Amino acid and peptide conjugates of quinine were synthesized using microwave irradiation in 52–95% yields using benzotriazole methodology. The majority of these conjugates retain in vitro antimalarial activity with IC50 values below 100 nm, similar to quinine.

Total synthesis of cyclic heptapeptide Rolloamide B.

The first total synthesis of Rolloamide B, a cyclic proline-enriched heptapeptide, is reported. This work features solution phase benzotriazole-mediated peptide synthesis ligating native amino acids.

Design, synthesis, and molecular modelling of pyridazinone and phthalazinone derivatives as protein kinases inhibitors

The design and synthesis of pyridazinone and phthalazinone derivatives are described. Newly synthesized compounds were tested on a panel of four kinases in order to evaluate their activity and potential selectivity. In addition, the promising compounds were tested on four cancer cell lines to examine cytotoxic effects. The compounds inhibited DYRK1A and GSK3 with different activity. SAR analysis and docking calculations were carried out to aid in the interpretation of the results. Taken together, our findings suggest that pyridazinone and phthalazinone scaffolds are interesting starting points for design of potent GSK3 and DYRK1A inhibitors.

Similarity analysis, synthesis, and bioassay of antibacterial cyclic peptidomimetics

Summary The chemical similarity of antibacterial cyclic peptides and peptidomimetics was studied in order to identify new promising cyclic scaffolds. A large descriptor space coupled with cluster analysis was employed to digitize known antibacterial structures and to gauge the potential of new peptidomimetic macrocycles, which were conveniently synthesized by acylbenzotriazole methodology. Some of the synthesized compounds were tested against an array of microorganisms and showed antibacterial activity against Bordetella bronchistepica, Micrococcus luteus, and Salmonella typhimurium.

Synthesis, molecular modeling and anti-inflammatory screening of new 1,2,3-benzotriazinone derivatives

Several new 4(3H)-1,2,3-benzotriazinone derivatives were synthesized and tested for their anti-inflammatory activity and ulcerogenic effect. A docking study on the COX-2 binding pocket has been carried out for the target compounds to rationalize the possible selectivity. Among the tested compounds, the benzotriazinones linked to either thiadiazole (8) or oxadiazole (9) evoked the highest anti-inflammatory activity as well as the best binding profiles into the COX-2 binding site.

Introduction of histidine units using benzotriazolide activation

Nα‐Boc‐Nim‐(4‐toluenesulfonyl‐l‐histidylbenzotriazole) enables convenient acylation of N‐, O‐, S‐, and C‐nucleophiles with no detectable racemization. We report efficient syntheses of novel histidine‐containing di‐, tri‐, and tetra‐peptides and models for the preparation of potentially biologically active histidine N‐, O‐, S‐, and C‐conjugates. Copyright

SYNTHESIS OF SOME NEW 3-MERCAPTO-5-SUBSTITUTED-1,2,4-TRIAZINE-S-TRIAZOLES FOR EVALUATION AS ANTIBACTERIAL AGENTS

Abstract The synthesis of several S- and N-substituted derivatives of 5-[(5,6-diphenyl-1,2,4-triazin-3-yl)oxymethyl]-s-triazole-3-thiol. 2-[(5-6-diphenyl-1,2,4-triazin-3-yl)-oxymethyl]-5,6-dihydrothiazolo[3,2-b]-s-triazole, 2-[(5,6-diphenyl-1,2,4-triazin-3-yl) oxymethyl]-6,7-dihydro-s-triazolo-[5,1-b]-1,3-thiazine, 2-[(5,6-di-phenyl-1,2,4-triazin-3-yl)oxymethyl]-5,6-dihydrothiazolo-[3,2-b]-s-triazol-6-one and 2-[(5,6-diphenyl-1,2,4-triazin-3-yl)oxymethyl]-6-phenylthiazolo-[3,2-b]-s-triazole is reported. All the novel compounds have been screened for antibacterial activity and none of them showed noteworthy activity.

Cysteinoyl- and cysteine-containing dipeptidoylbenzotriazoles with free sulfhydryl groups: easy access to N-terminal and internal cysteine peptides.

N‐Protected cysteines 4a–c each with a free sulfhydryl group were prepared in 70–75% yields by treatment of l‐cysteine with 1‐(benzyloxycarbonyl) benzotriazole (Cbz‐Bt) 1a, N‐(tert‐butyloxy‐carbonyl)benzotriazole (Boc‐Bt) 1b, and 1‐(9‐fluorenylmethoxy‐carbonyl)benzotriazole (Fmoc‐Bt) 1c, respectively. N‐Protected, free sulfhydryl cysteines 4a–c were then converted into the corresponding N‐protected, free sulfhydryl cysteinoylbenzotriazoles 7a–c (70–85%), which on treatment with diverse amino acids and dipeptides afforded the corresponding N‐protected, free sulfhydryl N‐terminal cysteine dipeptides 8a–e and tripeptides 8f–h in 73–80% yields. N‐Protected, free sulfhydryl cysteine‐containing dipeptides 9a,b were converted into the corresponding N‐protected, free sulfhydryl dipeptidoylbenzotriazoles 10a,b (69–81%), which on treatment with amino acids, dipeptides, and a tripeptide afforded internal cysteine tripeptides 11a–c, tetrapeptides 11d,e and pentapeptide 11f, each containing a N‐protected, free sulfhydryl groups in 70–90% yields under mild conditions. Treatment of N‐protected, free sulfhydryl cysteinoylbenzotriazole 7a with diamines 12a,b afforded directly the cysteine‐containing disulfide‐bridged cyclic peptides 14a,b in 50% yields.

Cysteinoyl- and Cysteine-containing Dipeptidoylbenzotriazoles with Free Sulfhydryl Groups

N‐Protected cysteines 4a–c each with a free sulfhydryl group were prepared in 70–75% yields by treatment of l‐cysteine with 1‐(benzyloxycarbonyl) benzotriazole (Cbz‐Bt) 1a, N‐(tert‐butyloxy‐carbonyl)benzotriazole (Boc‐Bt) 1b, and 1‐(9‐fluorenylmethoxy‐carbonyl)benzotriazole (Fmoc‐Bt) 1c, respectively. N‐Protected, free sulfhydryl cysteines 4a–c were then converted into the corresponding N‐protected, free sulfhydryl cysteinoylbenzotriazoles 7a–c (70–85%), which on treatment with diverse amino acids and dipeptides afforded the corresponding N‐protected, free sulfhydryl N‐terminal cysteine dipeptides 8a–e and tripeptides 8f–h in 73–80% yields. N‐Protected, free sulfhydryl cysteine‐containing dipeptides 9a,b were converted into the corresponding N‐protected, free sulfhydryl dipeptidoylbenzotriazoles 10a,b (69–81%), which on treatment with amino acids, dipeptides, and a tripeptide afforded internal cysteine tripeptides 11a–c, tetrapeptides 11d,e and pentapeptide 11f, each containing a N‐protected, free sulfhydryl groups in 70–90% yields under mild conditions. Treatment of N‐protected, free sulfhydryl cysteinoylbenzotriazole 7a with diamines 12a,b afforded directly the cysteine‐containing disulfide‐bridged cyclic peptides 14a,b in 50% yields.