الفهرس 
AIM OF THE WORKOnly 14 pages are availabe for public view
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Abstract
Globally, cancer kills approximately 20,000 people a day, a number projected to increase dramatically in coming decades, so treatment of cancer becomes a global challenge and an urgent need, the use of chemotherapy which targeting tumor progress is one of the most common techniques. The need of highly effective drug with low side effects, and inexpensive is vital and important in order to protect millions of patients around the world from certain death. In this work present, The esterification reaction of trimellitic anhydride chloride with N-(hydroxymethyl)phthalimide, N-(2- hydroxyethyl)phthalimide or N-(hydroxymethyl)thalidomide afforded novel cyclic imide-ester derivatives; phthaloyl-phthalic anhydride methyl ester, phthaloyl-phthalic anhydride ethyl ester and thalidomide-phthalic anhydride methyl ester, respectively. The newly cyclic imide-ester derivatives appearedvery useful for preparation of new hybrid structure of bis-N-substituted phthalimide and phthalimide-thalidomide moieties. Further reactions of the resulted esters with different amino acids i.e., glycine, glycine ethyl ester, alanine and phenylalanine under reflux in dry DMF yielded the phthaloyl derivatives in more than 70% yield. The reaction of tryptamine hydrochloride with the newly cyclic imide-ester derivatives in base catalyzed reaction using triethyl amine under reflux in dry DMF afforded N-tryptamino-bisphthalimide methyl ester, N-tryptamino-bis phthalimide ethyl ester and Ntryptamino-phthalimide thalidomide methyl ester respectively. The structure for the above mentioned derivatives were elucidated on the basis of their spectral data IR, 1H-NMR, 13C-NMR and Electrospray ionization high resolution mass spectrometry (ESIHRMS) and MALDI mass spectrometry. All newly synthesized compounds were examined for their in vitro antitumor activity against Human hepatocellular carcinoma cell line (Hep-G2) and Human Caucasian breast adenocarcinoma (MCF-7) by using MTT method. Screening for antitumor activity included measurement of % of the in vitro cell inhibition as well as Median lethal concentration (LC50) (μM). Cell viability was assessed by the active mitochondrial reduction of yellow MTT to form blue insoluble formazan crystals. Results revealed that derivatives containing phthalimide core exhibited significant Cytotoxic activity against MCF-7 and Hep-G2 cell lines than those containing thalidomide skeleton. The obtained results supported the concept that phthalimide moiety is an essential pharmacophoric fragment in thalidomide structure.