{'fraction_non_alphanumeric': 0.025876940770557792, 'fraction_numerical': 0.013801035077630822, 'mean_word_length': 5.4684014869888475, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
SYNTHESIS OF A BENZODIOXINIC ANALOGUE OF ELLIPTICINE AND EVALUATION OF ITS ANTITUMOR ACTIVITY

A benzodioxinic analogue of Ellipticine was synthesized, using two strategies both involving a Diels Alder cycloaddition of furobenzodioxin. Antitumor activity was evaluated in vitro and in vivo on Β 16 melanoma and Ρ 388 Leukemia.. Introduction Ellipticine i (5,11-dimethyl-6H-pyrido [4,3-b] carbazole) is a naturally-occuring alkaloid which is known for its broad spectrum of antineoplastic activity (1). A number of structure-activity studies have already been made to determine the essential structural requirements associated with its antitumoral activity. In particular, it was shown that the replacement of the carbazole nitrogen atom by either sulfur or oxygen resulted in loss of activity (2) and that substituting either benzoxathiine or benzothiazine substructures for the indolo heterocyclic nucleus also resulted in loss of activity (2). However, in these two cases the biological studies were performed with demethylated analogues of ellipticine and it had been previously shown that the presence of the 5 and 11 methyl groups was critical for activity (3,4). Through other studies, W. A. Denny identified dibenzo [1,4] dioxin as a novel DNA-intercalating chromophore with in vivo antitumor activity (5). Moreover we showed that tetracyclic dioxinocoumarines exhibited promising biological activities and in particular inhibited the growth of HeLa cells whether UVA radiations were present or not (6). With the aim to investigate its biological properties as a potential antitumor agent we therefore synthesized a tetracyclic hybrid molecule 2 that includes a benzodioxinic substructure and the isoquinoline moiety of ellipticine.