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Part-IIIAdvances Dihydropyridines and …for their MDR reverting ability in human KB cells. PAK-1 52 was found to be a weakercalcium channel-blocking activity, when compared with other members of the seriesincluding the standard nifedipine but completely reverses the drug resistance. Though,nifedipine 53 and other analogs are better at blocking calcium channels than PAK-1, butthey only partially reverse the resistance. 96Two isomers of teludipine 54, R-enantiomer (GR66234A) and L-enantiomer (GR66235A) which were originally developed as a new lipophilic calcium channel blocker byGlaxo were evaluated for daunorubicin resistance reversal activity and found to be moreeffective than verapamil. Additionally, the difference in activity was also found ondifferent cells. Verapamil and the enantiomers of teludipine are more active in ARNIIcells than in MCF 7/R cells. There were no apparent differences in cellular daunorubicinaccumulation between ARNII and MCF 7/R following exposure to teludipine, nodifferences in intracellular daunorubicin distribution in the presence of either MDRreversing agent was observed. 97In an attempt to characterize chemosensitizer domains on Pgp, Boer et al., found thatDHPs label multiple chemosensitizer domains on Pgp, distinct from the vinblastineinteraction site. (-)-[3H]BZDC-DHPs 55 represents a valuable tool to characterize themolecular organization of chemosensitizer binding domains on Pgp by both reversiblebinding and photo-induced covalent modification. It provides a novel simple screeningassay for Pgp active drugs. Photoreactive DHPs, BZDC-DHPs (2,6-dimethyl-4-(2-(trifluoromethyl)-phenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid {2-[3-(4-benzoylphenyl)propionylamino]ethyl}ester ethyl ester), and its tritiated derivative weresynthesized as novel probes for human Pgp. (-)-[3H]BZDC-DHPs specificallyphotolabeled Pgp in membranes of multidrug-resistant CCRF-ADR5000 cells. Inreversible labeling experiments a saturable, vinblastine-sensitive and high-affinitybinding component was present in CCRF-ADR5000 membranes but absent in thesensitive parent cell line. Binding was inhibited by cytotoxics and knownchemosensitizers with a Pgp. The DHPs such as niguldipine and a structurally relatedpyrimidine stereoselectively stimulated reversible (-)-[3H]BZDC-DHPs binding,suggesting that more than one DHPs molecule can bind to Pgp at the same time. 98-99410