The multidrug-resistance (MDR)-reversal activity of 232 phenothiazines and structurally related compounds was tested in MDR P388 cells. Such activity was found among compounds exhibiting two ring structures (phenyl, cyclopentyl, cyclohexyl, thienyl or 5-norbornen-2-yl but not pyridinyl) linked by a variety of bridge types and possessing a secondary or tertiary amine group. Among 192 such compounds, 31.8% displayed good activity (MDR-reversal ratio, greater than or equal to 10) and 8.3%, outstanding activity (MDR-reversal ratio, greater than or equal to 30). In a subgroup comprising 56 compounds with a carbonyl residue, 4 with sulfuryl residue and 1 with thienyl residue, 42.7% showed good activity and 18%, outstanding activity. The contribution of these residues to the MDR-reversal activity was particularly evident among compounds containing a cyclic tertiary amine. Among 49 such compounds, 51% displayed good activity and 20.4%, outstanding activity, whereas among the 85 compounds lacking such groups, only 31.8% showed good activity and 4.7%, outstanding activity. Enhancement of this activity by the carbonyl group is also obtained when the latter is part of an amide bond of a tertiary amine. As compounds with a carbonyl group located on the rings, on the bridge to the amine group or beyond the amine are efficient MDR reversers, it seems that the exact molecular location of the carbonyl group is not critical for the elicitation of this activity.

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Dipyridamole restores sensitivity to Adriamycin (ADR) in drug‐resistant cells. In an effort to elucidate the relationship between activity and chemical structure of dipyridamole, the ability to enhance the growth inhibitory effect of ADR, in multidrug‐resistant (MDR) P388 murine leukemia cells, was determined for 43 derivatives and related compounds. Since both substituted pyrimidopyrimidines and pteridines enhanced the growth‐inhibitory effect of ADR in drug resistant cells, the core skeleton may not be directly involved and rather serve as a carrier for the substituents connected with this activity. The exact positions of the active substituents on the core skeleton did not seem to be critical for exertion of the activity. Activity was dependent on the presence of 3 tertiary amine groups. However, not all tertiary amines showed the same potency which might be related to the degree of basicity and/or the spatial structure of these groups. The most active derivatives carried piperidine and pyrrolidine groups while derivatives with thiomorpholine, 3‐hydroxypiperidine or dimethylamine groups had low activity. Activity was also dependent on the presence of a substituent with partial electronegative charges as found in a diethanolamine group. However, this function could be carried out, with even higher efficiency, by a substituent containing 6π electrons.

Ocular complications after treating children with retinoblastoma are common and may seriously affect the quality of life of children surviving the primary malignancy.

Prognostic implication of serum cytokeratin 19 fragments (CYFRA 21-1) was explored in 60 advanced NSCLC patients, whereas in 45 patients assessable for serological response a X35% CYFRA 21-1 decline after two chemotherapy cycles was strongly associated with non-progression (NP), defined as a sum of objective response (OR) þ stable disease (Po0.0001) and survival (P ¼ 0.0002). Association of OR with survival was not significant. In multivariate survival analysis, X35% marker decline and radiological NP status were found as major determinants of prolonged survival with RR: 0.37 (P ¼ 0.01) and 0.63 (P ¼ 0.01), respectively. In advanced NSCLC patients, NP reflects therapeutic efficacy better than traditional OR. CYFRA 21-1 X35% decline seems to be a reliable surrogate marker of treatment efficacy in terms of survival.