5237
Marian Nady Aziz
Design and Synthesis of Pharmacological Active Nitrogen-Containing Heterocycles Utilizing Molecular Modeling Techniques
Spiro-compound, Indole, Piperidone, Azafluorene, Indenopyridine, Azaphenanthrene, Benzoquinoline, Benzocycloheptapyridine, Antitumor, Bronchodilator, Pharmacophore, QSAR, DFT.
The original work describes design and synthesis of novel heterocyclic compounds of potential biological/pharmacological properties against universally distributed diseases especially, as antitumor and bronchodilatory active agents, through facile synthetic pathways.1''-Alkyl-4'-aryl-5''-(arylmethylidene)-1'-methyl-dispiro[3H-indole-3,2'- pyrrolidine-3',3''-piperidine]-2(1H),4''-diones were regioselectively synthesized through dipolar cycloaddition reaction of azomethine ylides. Some of the synthesized compounds showed antitumor activities against HeLa (cervical) and HepG2 (liver) carcinoma cell lines with potency higher than that of the standard reference used (cisplatin and doxorubicin hydrochloride). Molecular modeling studies (3D-QSAR pharmacophore and 2D-QSAR) explained the antitumor variability of the tested compounds and determined the important parameters controlling bio-activities.Bronchodilatory active agents (azafluorenes, azaphenanthrenes and benzocycloheptapyridines) were synthesized in facile synthetic pathways. Computational chemistry studies employing AM1, PM3 and DFT techniques, were undertaken revealing good correlations of the experimental (X-ray studies) and theoretical optimized parameters. The conformationaldifferences observed due to theoretical and experimental studies were also rationalized
2016
M.Sc
Helwan
Science