Download (4Mb) - Etheses - Saurashtra University

Summary and Conclusionreverting activity on MDR1-gene transfected mouse lymphoma cell line (l5178 y).Verapamil was taken as a positive control. Few derivatives, namely 4-chloro-2-(2-chloroethyl)-5-(4-methylphenyl)thieno[2,3-d]-pyrimidine VIxiv, 2,5,6-trimethylthieno[2,3-d]pyrimidin-4(3H)-oneVxxvi, 4-chloro-2-(2-chloroethyl)-5,6-dimethylthieno[2,3-d]pyrimidineVIxv, 4-chloro-2-(2-chloroethyl)-5,6,7,8-tetrahydro-benzo[4,5]-thieno[2,3-d]pyrimidine VIv, 2-methylquinazolin-4(3H)-one Vxxx, 2-chloro-methyl-3Hbenzo[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-tetra-hydro-3H-9-thia-1,3,7-triaza-fluoren-4-one Vx, 4-chloro-2-chloromethyl-6,7,8,9-tetra-hydro-5H-10-thia-1,3-diaza-benzo[a]azulene VIvi and 4-chloro-2-(chloromethyl)-5-(4-methoxyphenyl)thieno[2,3-d]pyrimidine VIvii showed moderate activity in inhibiting the Pgp,which is reflected by fluorescence activity ratio. None of the compounds showedcytotoxic effect in the when measure at 4 micromol/ml/1million cells concentration,which is desirable. This means that the above stated compounds were moderatelyeffective in reversal of MDR efflux pump activity. Verapamil was taken as a standard inthis study.Part-III of the thesis deals with “Synthesis, Characterization and Anticancer Activity ofsome Aza-analogue of DP-7”.Literature survey reveals that DP-7 (dihydropyridine derivative) is a potent multi drugreverting agent and on the other hand, monastrol (dihydropyrimidine derivative) is potentinhibitor of Eg5 that inhibits ATP hydrolysis through an allosteric mechanism. Thus, itwas thought to hybridize the structural features of these two potent anticancer moleculesso that multidrug reverting activity as well as Eg5 inhibitor activity can be obtained by asingle molecule. These hybridized molecules are aza analogues of the DP-7, bearingvarious substitutions on the 4 th position of the dihydropyrimidine ring.In all 30 dihydropyrimidine derivatives has been synthesized in this part which werecharacterized by spectral data. The newly synthesized derivatives were screened onMDR1-gene transfected mouse lymphoma cell line (l5178 y) for MDR reversal effects atnon toxic concentrations taking verapamil as a standard. The four compounds namely 5-benzoyl-6-methyl-4-(1-naphthyl)-3,4-dihydropyrimidin-2(1H)-one VIIvii, 4-(2,5-dimethoxy phenyl)-6-methyl-5-(1-phenylvinyl)-3,4-dihydro-pyrimidin-2(1H)-one VIIix,491