الفهرس | Only 14 pages are availabe for public view |
Abstract According to the previously described routes, new thirty-six compounds were synthesized. Reaction times were monitored using TLC plates, the target compounds were purified by crystallization and the structure elucidation of these compounds were fulfilled based on spectra analysis, IR, 1H-NMR, 13C-NMR, mass spectroscopy and elemental analyses. In vitro biological screening via fluorometric method against hMAOs was done for all compounds and the results revealed that all hybrids showed good activities against both hMAO-A and hMAO-B enzymes. benzimidazole hybrids 74 and 75 exhibited best MAO-B inhibitory actions, while hydroxy biphenylpiperazine hybrids 92 and 93 showed the best MAO-A inhibitory action. Kinetic, reversibility and cytotoxicity studies were performed for compound 75 as the most potent one, it was concluded that it is reversible and mixed competitive inhibitor and non-cytotoxic. Molecular modeling of the most active hybrids 74, 75, 92 and 93 with MAO-A and MAO-B revealed their good binding affinity as they bound to the essential amino acids in the active sites using MOE© software. Accordingly, 1,4- biphenylpiperazine derivatives can be considered as a promising lead to produce more potent and safer MAO inhibitors for management of various neurological disorders as Parkinson, Alzhiemer’s diseases, psychosis like depression, anxiety disorders. |