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4.5.2 Discussion:Part-IIResults and DiscussionMDR reversal assay has gained importance in view of many cancerous cells developingmultiple drug resistance (MDR) due to incorporation of MDR-1 gene coding of P-gp, aglycoprotein involved in MDR. The glycoprotein P-gp is driven by ATP and isresponsible for efflux of drug from the cancerous cells leading to MDR. Therefore, MDRreversal agents are being exploited as potential anticancer agents. 7,8Condensed pyrimidines synthesized in this part of the thesis were tested for MDRreversal activity on MDR -1 gene transfected cell line 15178 by flow cytometry. Total of52 compounds were tested for the MDR reversal activity. Details of the test protocol aregiven earlier. The tests were carried out in three sets with veerapamil as positive control.The great majority of the compounds were ineffective on the MDR reversal efflux pumpactivity. The majority of the compounds were identified and characterized in this groupas ineffective compounds when tested in 4 micro mol conc. No direct cytotoxic effectwas found at the above concentration.However, compounds 4-chloro-2-(2-chloroethyl)-5-p-tolylthieno[2,3-d]pyrimidine VIxiv,2,5,6-trimethylthieno[2,3-d]pyrimidin-4(3H)-one Vxxvi, 4-chloro-2-(2-chloroethyl)-5,6-dimethylthieno[2,3-d]pyrimidine VIxv, 4-chloro-2-(2-chloroethyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidineVIv, 2-methylquinazolin-4(3H)-one Vxxx, 2-chloromethyl-3H-benzo[4,5]thieno[3,2-d]pyrimidin-4-oneVxiv, 9-methoxy-2-chloromethyl-3H-benzo[4,5]thieno[3,2-d]pyrimidin-4-one Vxv, 2-chloromethyl-3,5,6,7,8,9-hexahydro-10-thia-1,3-diaza-benzo[a]azulen-4-one Vvii, 7-benzyl-2-chloromethyl-5,6,7,8-tetrahydro-3H-9-thia-1,3,7-triaza-fluoren-4-oneVx, 4-chloro-2-chloromethyl-6,7,8,9-tetrahydro-5H-10-thia-1,3-diaza-benzo[a]azuleneVIvi and 4-chloro-2-(chloromethyl)-5-(4-methoxyphenyl)thieno[2,3-d]pyrimidine VIvii showed moderate activity which isexhibited by fluorescence activity ratio. None of the compounds showed cytotoxic effectin the above said concentration which is desirable. This means that the above statedcompounds were moderately effective in reversal of MDR efflux pump activity.360