Salwa Elmeligie

Synthesis of some quinoxaline derivatives containing indoline-2,3-dione or thiazolidinone residue as potential antimicrobial agents

The synthesis of some quinoxaline derivatives containing indoline-2,3-dione or thiazolidinone residue is described. The synthesized derivatives were screenedin vitro for their growth inhibitory activity against six species of bacteria, viz.Staphylococcus aureus, Streptococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens andMycobacterium semegmatis. Most of the compounds exhibited antimicrobial activity especially those having indoline-2,3-dione moiety.

Design, synthesis and cytotoxic activity of certain novel chalcone analogous compounds

A series of chalcone analogous compounds were designed and synthesized. Replacing/substituting the enone or ethylenic bridge of the parent chalcone with rigid heterocyclic moieties or substituted aromatic amines gave nineteen target compounds. Their cytotoxic activities were screened against both breast and liver cancer cells as well as breast and liver normal cells. Target compounds were also evaluated for their inhibition activity of tubulin beta polymerization. Target compound 2e, 3a, 3b, 3c, 4a-4d, 5a, 5b and 6 showed broad spectrum excellent anticancer activity against both MCF-7 and HepG2. Compound 4a showed the most TUBb inhibition activity.

Synthesis and cytotoxic activity of certain trisubstituted azetidin-2-one derivatives as a cis-restricted combretastatin A-4 analogues

Novel series of 1,3,4-trisubstituted azetidin-2-one derivatives 8a–p were synthesized and proposed as cytotoxic agents acting via inhibition of tubulin at the colchicine binding site. The design of the target compounds was based upon modification in the structure of the vascular targeting agent combretastatin A-4 (CA-4). The cis double bond linker in CA-4 was replaced with the azetidin-2-one ring aiming to prevent the cis/trans isomerization that suppresses the activity of CA-4, thereby enhancing its antiproliferative activity. All new compounds were investigated in vitro against MCF-7 and HCT-116 cell lines. The inhibition of tubulin polymerization by four most potent compounds 8g, 8j, 8n and 8o was also evaluated. The synthesis of the final targets was achieved adopting Staudinger reaction. Molecular modeling studies were performed to rationalize the biological results.

New 3‐Substituted‐2‐(4‐hydroxyanilino)pyridine Derivatives: Synthesis, Antitumor Activity, and Tubulin Polymerization Inhibition

A series of new pyridine derivatives 4a–c, 5a–d, 6a–d, 7a–f, and 8a–f structurally related to ABT‐751 were synthesized and characterized by spectroscopic means and elemental analysis. All the synthesized compounds were tested for their cytotoxic activity in vitro against the HCT‐116 and HepG‐2 cancer cell lines using the MTT assay. The results showed that compound 8d has higher cytotoxic activity than the reference antimitotic agent colchicine, against both tested cell lines, with IC50 = 0.52 and 1.40 μM, respectively. The three most active compounds, 5d, 8b, and 8d, were further screened in vitro for inhibition of tubulin and showed remarkable results in comparison to colchicine.

Design and Synthesis of Pyridazine Containing Compounds with Promising Anticancer Activity

Certain pyridazine containing compounds 2a-f, 3a, b, 4a, b, 5a, b, 6a and b were synthesized and characterized by spectroscopic means and elemental analysis. All the synthesized compounds were screened for their cytotoxic activity in vitro on colon cancer cell line (HCT-116) and breast cancer cell line (MCF-7). In addition, the antitumor activity of the synthesized compounds was tested in vivo against Ehrlichs ascites carcinoma (EAC) solid tumor grown in mice. The in vitro vascular endothelial growth factor receptor (VEGFR) enzyme inhibition assay was carried out for the most active compounds at a single dose of 10 µM. The obtained results revealed that compound 5b, which showed potent cytotoxic activity against HCT-116 also, exhibited the highest inhibition in the VEGFR kinase assay (92.2%).

Synthesis of pyrazolo[3,4-b]pyridine and pyrido[2',3':3,4]pyrazolo [1,5-a]pyrimidine derivatives

The synthesis of two series of 1-phenyl and 1H-pyrazolo[3,4-b]pyridine is described. Thus, reacting 5-amino-1-phenylpyrazole with chalcone analogues gave 4,6-diarylpyrazolo[3,4-b]pyridine derivatives. While, reacting the same starting material with benzylidene derivatives of ethyl cyanoacetate and malononitrile resulted in 4-oxo and 4-aminopyrazolo[3,4-b]pyridine derivatives, respectively. The synthesis of 3-amino-4,6-diarylpyrazolo[3,4-b]pyridines starting from pyridine was also described. Thus, chlorination of 4,6-diarylpyridone derivatives and their subsequent cyclisation with hydrazine hydrate afforded 3-amino-4,6-diarylpyrazolo[3,4-b]pyridines. Reaction of the latter compounds with acetylacetone, ethyl ethoxymethylenecyanoacetate and chalcone analogue gave the tricyclic pyrido[2′,3′: 3,4]pyrazolo[1,5-a]pyrimidines. The structures of the products were confirmed by spectral data.