Antileukemic P388 activities

Although cephalotaxine itself exhibits no significant antileukemic activity, a number of naturally occurring esters of the alkaloid, the harringtonines (107-110), are active against LI 210 and P388 leukemias in mice (89,100, 108), and so some attention has been devoted to the synthesis of the dicar-boxylic acid side chains (see also Section IV,A). 

Nitidine and garonine are known as potential anti-tumour, antileukemic, and antiviral agents [9,52,98]. Some synthetic 12-alkoxyderivatives of 2,3,8,9-tetramethoxy QBA are potent in vitro inhibitors of the growth of P388 cells [144]. Nitidine, isolated firom Kenyan Toddalia aculeata Pers. (synonym T. asiatica (L.) Lamk.) has shown antimalarial activity [145]. Nitidine and fagaronine have been foimd to inhibit HTV reverse transcriptase [146]. 

In 1974, extracts of the tiny ( 5 mm) marine tube worm Cephalodiscus gilchristi collected off South Africa were found to be active in the NCI s primary assay, the murine lymphocytic leukemia P388. Fifteen years of relentless research by Pettit s group culminated in the isolation of 139 mg of the major bioactive component, cephalostatin 1, from 166 kg wet weight of the tube worm, and its structural elucidation. [2] This phase was summarized [3] as follows Interest in such a powerfully antileukemic agent as cephalostatin 1. .. has prompted Americans to dive extensively at a depth of 20 meters to collect... 

Methyl-1,3-dihydropyrrolo[ 1,2-c]thiazole-6,7-biscarbamates have been described as active compounds against murine P388 lymphocytic leukemia <87JMC2109>. Several 5-aryl-2,3-dihydro-pyrrolo[2,l-fe]thiazole-6,7-dimethanol-6,7-bis(isopropylcarbamate)s were tested for growth inhibitory activity with the HL-60 human promyelocytic leukemia cell line. The 5-phenyl, 5-(4-fluorophenyl), and 5-(3,4-dichlorophenyl) have antileukemic activity. These compounds were also cytotoxic to HT-29 human colon carcinoma cells <88JMC1427>. 

Rocaglamide (378) is a natural product isolated from the roots and stems of Aglaia elliptofolea Meer. (Meliaceae). It displays antileukemic activity against P388 lymphocytic leukemia in mice and... 

Some novel hexacyclic and 7,9-disubstituted pentacyclic derivatives of camptothecin were synthesized by Terasawa et al. They were evaluated for in vitro cytotoxic activity against P388, HOC-21, and QG-56 and in vivo antileukemic activity against P388 in mice. Hexacyclics 213 and 215 have an additional 5-, 6-, or 7-membered ring cyclized at positions 7 and 9 of the camptothecin moiety. They were prepared by intramolecular cyclization of pentacyclic camptothecin derivatives of bicyclic amino ketone 212 or 214 and a tricyclic ketone 211, respectively (Scheme 46) (94JME3033). 

We next examined in vivo antileukemic activity of SMDC compared with ara-C against implanted mouse leukemia P388 (10 ) in CDFl mice, with doses indicated in Table 3 given ip once each day on days 1-5. As described in Table 3, ara-C was much more potent than SMDC at every dose. We found that SMDC was not a substrate for cytidine deaminase from... 

In vivo antileukemic activity of CNDAC, cytarazid, and ara-C was also examined against ip-implanted P388 in CDFi mice (Table 8). CNDAC administered ip once a day on days 1 and 5 at 100 mg/kg had a T/C of 183%, while cytarazid and ara-C on the same... 

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