الفهرس 
Chemistry of phthalazinesOnly 14 pages are availabe for public view
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Abstract
Cancer is second cause of death after heart attack disease according to WHO reports. Regarding the uncontrolled growth of cancer, many researchers do their efforts to find new and safe anticancer drugs. Notably, heterocyclic compounds have a vital role in drug design and development of bioactive compounds as anticancer agents. Among these compounds, phthalazine occupied great interest in medicinal chemistry. the presence of two nitrogen atoms in phthalazine core confer promising biological activities such as anticancer and antimalaria.
This thesis describes synthesis of new phthalazine derivatives through nucleophilic reaction a with the key intermediates to the aim to evaluate their anticancer activities.
The thesis consists of the following parts:
1) Introduction: this section presented literatures survey of the synthetic approaches of phthalazine core as well as their biological applications.
2) Results and Discussion: this part demonstrated the preparation of the target conjugates bearing phthalazine core in addition to the establishment of these conjugates and their intermediates via different spectroscopic methods. The biological evaluation of the synthesized illustrated below:
The synthetic pathways followed in the preparation of target compounds. In this part the authors synthesis 2-(4-methylbenzoyl) benzoic acid 3 by the reaction of toluene with phthalic anhydride under Friedel Craft’s condition. Condensation of benzoic acid derivative with hydrazine hydrate in boiling ethanol afforded the target compound give 4-(p-tolyl)phthalazin-1(4H)-one (4).
The key intermediates p-toulyl chlorophthalazine 4 derivative was obtained pon reaction with phosphorus oxychloride to give the corresponding 5 with large chemical diversity on the heteroaromatic nucleus, good yield, short reaction time and high degree of purity. The key intermediate p-toulyl chlorophthalazine 5 was used for the diversification of the thalazine core at the C-4 position. Thus, the phthalazine derivatives with C4-amine side chains and different carbon spacers between the two nitrogen were synthesized after reaction of the key intermediates, 5 with excess of appropriate amines , through a nucleophilic substitution reaction with release of chloride at C-4 of the aromatic nucleus of phthalazine to get the free amine of phthalazine derivatives 6. The free amines of phthalazine cores reacted with cyantes and naphthalene derivatives to form the target conjugates of 7.
The installation of the intermediates and their corresponded conjugates was affirmed via different spectroscopic methods such as NMR, FTIR and mass spectrometery.
The in vitro anticancer screening of the phthalazine intermediates and their conjugates was evaluated against HCT-116 , HepG-2, MCF-7 cancer cell lines. the cytotoxicity of the synthesized compounds was screening against BJ-1 cell line. The results revealed the potency and selectivity of the target conjugates against cancer cell lines.2.
2) Materials and methods: this part illustrated the steps of the preparation of the starting p toulyl 1-chloro phthalazine and their free amines as well as the synthesized conjugates. Additionally the methodology of in vitro anticancer screening was presented in material and method part.
Conclusions
Newly synthesized phthalazine derivatives 5a-d and 7a,b with antiproliferative properties were established, characterized and evaluated against three human HCT-116, HepG-2, MCF-7 cancer cell lines and; BJ-1 normal cells. The conjuates showed potent activity against cancer cell lines, especially against HepG-2 Human cancer cell line.it is worth recalling that 5b-d, as well as 7a,b demonstrated their potency and selectivity towards HepG-2 cancer cell line with IC50s: 1.6, 1.5, and 1.6 µM as compared with the reference drug doxorubicin IC50: 3.8 µM.