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3.5 DiscussionPart-IIIResults and DiscussionIn the present report, hybrid derivatives (thio and oxo analogues) of DP-7(dihydropyridine) and monastrol (dihydropyrimidines) were synthesized to get the dualaction in cancer chemotherapy. The newly synthesized molecules were screened onMDR1-gene transfected mouse lymphoma cell line (l5178 y) for MDR reversal effects atnon toxic concentrations.MDR reversal assay has gained importance in view of many cancerous cells developingmultiple drug resistance (MDR) due to incorporation of MDR-1 gene coding of Pgp, aglycoprotein involved in MDR. The glycoprotein Pgp is driven by ATP and is responsiblefor efflux of drug from the cancerous cells leading to MDR. Therefore, MDR reversalagents are being exploited as potential anticancer agents. 9-10The four compounds from this series were very effective, namely 5-benzoyl-6-methyl-4-(1-naphthyl)-3,4-dihydropyrimidin-2(1H)-one (VIIvii), 4-(2,5-dimethoxyphenyl)-6-methyl-5-(1-phenylvinyl)-3,4-dihydropyrimidin-2(1H)-one (VIIix), 5-benzoyl-4-(3Hindol-3-yl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one(VIIx) and [6-methyl-4-(3-phenoxyphenyl)-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl](phenyl)methanone(VIIxxvii) when measured in 4 micromol/ml/1million cells. These compounds hadmoderate effect on the MDR reversal efflux pump activity.The substitution of 3-phenyloxy ring on 4 th phenyl ring in case of (VIIviii) resulted anineffective compounds while dimethoxy, indolyl and napthyl substituents are very activeas resistance modifiers The differences in biological effects can be explained by stericdifferences in binding abilities of compounds to Pgp. Direct evidence of the nature ofeffective binding of the four most effective compounds to Pgp could be obtained by X-raydiffraction of co-crystallizations.471