A novel series of 2-styrylquinazolin-4(3H-ones which inhibited tubulin polymerization and the growth of L1210 murine leukemia cells was discovered. Extensive structure-activity relationship studies suggest that the entire quinazolinone structure was required, but activity was further enhanced by halide or small hydrophobic substituents at position 6. These analogues did not substantially interfere with the binding of radiolabeled colchicine, vinblastine, or GTP to tubulin and weakly stimulated GTP hydrolysis uncoupled from polymerization. Several analogues have shown in vivo tumor growth inhibitory activity in the L1210 leukemia model, with the lead compound 5o exhibiting good antitumor activity against murine solid tumors as well as human tumor xenografts.

Studies that measure tumor blood flow are necessary to confirm that these effects are mediated by changes in tumor vasculature.

Neonatal thrombocytopenia is a potentially life-threatening complication of immune thrombocytopenic purpura (ITP). We followed 23 pregnant women who had either a history of ITP (11 women) or clinically active disease (12 women) to delineate the factors responsible for neonatal thrombocytopenia. No relation was observed between maternal and neonatal platelet counts (P greater than 0.5). Eleven women delivered thrombocytopenic children; antiplatelet antibodies were detectable in each mother, including five who were in clinical remission at delivery. The level of platelet-associated IgG in the mothers did not identify the neonates at risk for thrombocytopenia (P greater than 0.05). However, the level of maternal circulating antiplatelet antibody correlated with both the presence and the extent of neonatal thrombocytopenia (P less than 0.005). A discrepancy between maternal platelet count and maternal antibody level may be especially notable in mothers treated with steroids or splenectomy. Monitoring the level of circulating antiplatelet antibody may help in identifying and managing pregnant women with ITP at risk of delivering neonates with serious thrombocytopenia.

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(+)-Ptilocaulin, a novel cyclic guanidine extracted from the Caribbean sponge Ptilocaulis aff. P. Spiculifer, is reported to have broad spectrum antimicrobial activity in vitro as well as in vitro activity against L1210 murine leukemia. To more fully evaluate this compound as an anticancer agent, the in vitro cell growth inhibitory potencies of synthetic racemic ptilocaulin and ten clinical anticancer drugs were determined and compared in 16 different normal and transformed human and murine cell populations. Potency, expressed as the 50% inhibitory concentration (IC50), was determined by a tetrazolium reduction (MTT) assay. Ptilocaulin showed a fairly broad spectrum of in vitro activity against colon and mammary adenocarcinomas, melanomas, leukemias, transformed fibroblasts and normal lymphoid cells (IC50s 0.05- greater than 10 micrograms/ml). This activity was comparable to that of many of the clinical drugs, including vinca alkyloids, antibiotics, alkylators and antimetabolites. Cell viability was affected only after a 72 hr exposure to the compound. In a clonogenic assay, cytocidal effects were observed after 24-72 hr exposures to 10 x IC50 concentrations of ptilocaulin, as evidenced by failure of cells to resume growth after removal of the compound. Cytostatic effects were observed at less than or equal to IC50 concentrations, as evidenced by resumption of growth to near-control levels after removal of the compound. Ptilocaulin was toxic at 50 and 25 mg/kg in an in vivo L1210 tumor model and was ineffective at lower concentrations (T/Cs 100-112%). In vivo studies in a more sensitive tumor system are recommended but are limited by the lack of availability of sufficient quantities of the compound.