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Part-IIIAdvances Dihydropyridines and …Other studies, however, have concluded that inactivation of the spindle checkpointsensitizes cells to apoptosis induced by antimicrotubule drugs. 164-165 The relationshipbetween the spindle assembly checkpoint and inhibition of the mitotic kinesin motorprotein Eg5 is just beginning to be elucidated. In a recent study, Tao et al., 166 and Gregoryet al., 167 suggest that induction of apoptosis by an Eg5 inhibitor requires sustained mitoticarrest, followed by adaptation and slippage into the next G1 phase.In recent years, dihydropyrimidinones and their derivatives have occupied an importantplace in natural and synthetic organic chemistry mainly due to their wide range ofbiological activities 168-169 , notably as calcium channel blockers. 170,171 Additionally, thestructurally related marine alkaloids batzelladine A 115 and B 116 were shown to be thefirst low molecular weight natural products to inhibit the binding of HIV gp-120 to CD4cells, so disclosing new vistas towards the development of AIDS therapy. 172NHNNHNHNH 2 NHNOOONNHBatzelladine AONHNNHOONH 2 NHNOOBatzelladine BNNHNHMore recently, ethyl 4-(3-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate,also known as monastrol 117, was identified as a novel lowmolecular weight cell-permeable molecule for the development of potentially newanticancer drugs. 173 This compound specifically affects the cell division (mitosis) by anew mechanism, which does not involve the binding to tubulin in contrast with thenatural taxanes, vinca alkaloids and epothilones. It has been established that the activityof monastrol is based on the specific and reversible inhibition of the motility of mitotickinesin Eg5, a motor protein required for bipolar spindle formation during mitosis. 174-178Moreover, Maliga et al., 179 have demonstrated that monastrol inhibits the motor activityof Eg5 by inhibiting ATP hydrolysis through an allosteric mechanism, whereas thecorresponding 4-hydroxyphenyl derivative is a weak Eg5 inhibitor and that (S)- monastrol436