Hassan M. Abdel-aziz

Synthesis, Characterization and Molecular Docking of Novel Bioactive Thiazolyl-Thiazole Derivatives as Promising Cytotoxic Antitumor Drug

Reactions of ethylidenethiocarbohydrazide with hydrazonoyl halides gave 1,3-thiazole or 1,3,4-thiadiazole derivatives according to the type of hydrazonoyl halides. Treatment of ethylidenethiosemicarbazide with hydrazonoyl halides and dimethylacetylene dicarboxylate (DMAD) afforded the corresponding arylazothiazoles and 1,3-thiazolidin-4-one derivatives, respectively. The structures of the synthesized products were confirmed by IR, 1H-NMR, 13C-NMR and mass spectral techniques. The cytotoxic activity of the selected products against the Hepatic carcinoma cell line (Hepg-2) was determined by MTT assay indicating a concentration dependent cellular growth inhibitory effect, especially for compounds 14c and 14e. The dose response curves indicated the IC50 (the concentration of test compounds required to kill 50% of cell population) were 0.54 μM and 0.50 μM, respectively. Confocal laser scanning imaging of the treated cells stained by Rhodamin 123 and Acridine orange dyes confirmed that the selected compounds inhibit the mitochondrial lactate dehydrogenase enzymes. The binding mode of the active compounds was interpreted by a molecular docking study. The obtained results revealed promising cytotoxic activity.

An efficient synthesis of functionalised 2-(heteroaryl)-3 H -benzo[f] chromen-3-ones and antibacterial evaluation

An efficient synthesis of 19 2-(heteroaryl)-3H-benzo[f]chromen-3-ones is described via reaction of 2-(3-hydroxyacry-loyl)-3H-benzo[f]chromen-3-one with various heterocyclic amines and active methylene compounds. The synthesised compounds, 18 of which are novel, were characterised on the basis of their elemental analysis and spectral data. Eight of the synthesised products were evaluated as antibacterial agents.

Synthesis and SAR Study of the Novel Thiadiazole–Imidazole Derivatives as a New Anticancer Agents

In the present study, a novel series of 2-(2-(3-aryl-5-substituted-1,3,4-thiadiazol-2(3H)-ylidene)hydrazinyl)-4,4-diphenyl-1H-imidazol-5(4H)-one derivatives were designed and prepared via the reaction of the most versatile, hitherto unreported 2-(5-oxo-4,4-diphenyl-4,5-dihydro-1H-imidazol-2-yl)-N-phenylhydrazinecarbothioamide with the appropriate hydrazonoyl halides. In addition, some thiazole derivatives were prepared. The structures of the newly synthesized compounds were established based on spectroscopic evidences and their alternative syntheses. Some of the newly synthesized compounds have been evaluated for their anticancer activity against a liver carcinoma cell line HEPG2-1. Moreover, their structure-activity relationship (SAR) was explored for further development in this area. The results indicated that many of the tested compounds showed moderate to high anticancer activity with respective to doxorubicin as a reference drug. Consequently, the new synthesized series of thiadiazole-imidazole derivatives are considered as powerful anticancer agents.

A NEW GENERAL METHOD FOR SUBSTITUTED 4-ALKYLTHIO-N-ARYLSULPHONYL-AMINO-2-PYRIDONES: REACTION OF KETENE-SS-ACETALS WITH ARYLSULPHONYLHYDRAZIDES

Abstract A novel and efficient method for the synthesis of substituted 4-alkylthio-N-arylsulphonylamino-2-pyridoms via the reaction of ketene-SS-acetals with N-cyanoacetoarylsulfonyl-hydrazides has been investigated. I-Arylsulfonylamino-pyrazolo[3,4-c]pyridine-2(1H)-ones have also been prepared from the reaction of 4-alkylthio-N-arylsulfonylamino-2-pyridones with hydrazines.

Green Synthesis and Molecular Docking of Thiazolyl-thiazole Derivatives as Potential Cytotoxic Agents

METHOD A series of novel thiazole derivatives were synthesized in a good yield via reaction of 2-(1-(4-methyl-2-phenylthiazol-5-yl)ethylidene)hydrazine carbothioamide with hydrazonoyl halides. The reaction was performed in the presence of DABCO as an organocatalyst in short reaction times, easy workup, good to excellent yields. The structure of the newly synthesized products was elucidated via elemental analysis, spectral data and alternative routes whenever possible. Ten compounds were evaluated for their anti-cancer activity against the colon carcinoma cell line (HCT-116). RESULTS & CONCLUSION The results revealed that most of the tested compounds showed high or moderate anti-cancer activity. The molecular docking of five novel thiazolyl-thiazole derivatives was performed by the Molecular Operating Environment (MOE) program.

Design and Synthesis of Imidazopyrazolopyridines as Novel Selective COX-2 Inhibitors

The usefulness of non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by their gastrointestinal side effects. Non-selective cyclooxygenases inhibitors interfere with both COX-1 and COX-2 isozymes. Since COX-1 mediates cytoprotection of gastric mucosa, its inhibition leads to the undesirable side effects. On the other hand, COX-2 is undetectable in normal tissues and selectively induced by inflammatory stimuli. Therefore, it is strongly believed that the therapeutic benefits derive from inhibition of COX-2 only. The presence of a strong connection between reported COX-2 inhibitors and cardiac toxicity encourages medicinal chemists to explore new scaffolds. In the present study, we introduced imidazopyrazolopyridines as new potent and selective COX-2 inhibitors that lack the standard pharmacophoric binding features to hERG. Starting from our lead compound 5a, structure-based drug-design was conducted and more potent analogues were obtained with high COX-2 selectivity and almost full edema protection, in carrageenan-induced edema assay, in case of compound 5e. Increased bulkiness around imidazopyrazolopyridines by adding a substituted phenyl ring(s) afforded less active compounds.