Mohamed Ramadan

Thieno[2,3-d]pyrimidines in the Synthesis of Antitumor and Antioxidant Agents

Dimethyl acetylenedicarboxylate, ethyl propiolate, and E‐dibenzoylethylene react with thienopyrimidines (cyclo‐pentyl, ‐hexyl, and ‐heptyl) derivatives to form thiazolo[3,2‐a]thieno‐[2,3‐d]pyrimidin‐2‐ylidene) acetates, thieno[2,3‐d]pyrimidin‐2‐ylthioacrylates, and thieno[2′,3′:4,5]pyrimido[2,1‐b][1,3]thiazin‐6‐ones, respectively. Reactions proceed via cyclization and thio‐addition processes. Some derivatives of thienopyrimidines showed high inhibition of Hep‐G2 cell growth compared with the growth of untreated control cells. However, the fused heptyl of thienopyrimidothiazines indicates a promising specific antitumor agent against Hep‐G2 cells with IC50 < 20 μM.

Reaction of amidrazones with 2,3-diphenylcyclopropenone: Synthesis of 3-(aryl)-2,5,6-triphenylpyrimidin-4(3 H )-ones

Amidrazones react with 2,3-diphenylcyclopropenone to give 3-aryl-2,5,6-triphenylpyrimidin-4(3H)-one derivatives in good yields. The synthesised compounds were characterised by spectroscopic tools and their structures confirmed by X-ray crystallography. A rational mechanism of formation of the products is presented.

Regioselective synthesis of 5-aminopyrazoles from reactions of amidrazones with activated nitriles: NMR investigation and X-ray structural analysis

N-Arylbenzamidrazones and ethyl 2-cyano-3-ethoxybut-2-enoate reacted together in ethanol and catalyzed by triethylamine (Et3N) to give 5-amino-3-methyl-1-(aryl(phenylimino)methyl)-1H-pyrazole derivatives. Reaction of the target amidrazones with bis-(methylthio)methylidene)malononitrile in EtOH/Et3N/DMF mixture proceeded to give the corresponding 5-aminopyrazoles. The structure of the obtained products was proved by IR, mass, and NMR spectra and elemental analyses. Two-dimensional NMR spectroscopy and X-ray structural analyses were used to differentiate the assigned structures from other possible ring systems and regioisomers. The reaction mechanism is discussed.

Novel pyrrol-2(3H)-ones and pyridazin-3(2H)-ones carrying quinoline scaffold as anti-proliferative tubulin polymerization inhibitors

A novel quinolinyl pyrrolone and quinolinyl pyridazinone derivatives has been synthesized and characterized using different spectroscopic and elemental analysis techniques. Most of the target compounds displayed promising antiproliferative activity; In general, the pyrrolone derivatives 4a-f exhibited higher antiproliferative activity than their corresponding pyridazinone. The pyrrolone 4f showed outstanding antiproliferative activity with moderate selectivity against CNS and renal cancer with selectivity ratio of 3.49 and 3.56, respectively. Compound 4e and 5d experienced tubulin polymerization inhibitory activity comparable to that of vincristine while 4c, 4e and 4d showed good BRAF kinase inhibition compared to Erlotinib. Docking of compound 4e into colchicine binding site and biological assay results revealed that these compounds act mainly through tubulin polymerization inhibitory mechanism and can exhibit pre G1 apoptosis and cell cycle arrest at G2/M phase.

Synthesis and evaluation of anticancer and PDE 5 inhibitory activity of spiro-substituted quinazolin-4-ones

A series of novel spiro-substituted 2,3-dihydroquinazolin-4(1H)-ones was synthesized and structurally confirmed by spectral analysis, screened for their anticancer activity at a concentration of 10 μΜ against a panel of 56 cell lines derived from nine different types of cancers, including leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast cancers. The synthesized compounds screened for their PDE 5 inhibitory activity and it showed encouraged activity compared to sildenafil.Graphical abstract