Cancer is the second leading cause of death worldwide. Drug researchers have encouraged by thegrowth of cancer incidence and low efficacy of current treatment to discover new drugs. Targeting specificregions of DNA to turn on/off genes has become an interesting research area. We evaluated the interaction of5-(benzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione derivatives with ctDNA using in vitro and in silico studies. MD simulation indicated that selectivity switched from AT to CG-rich DNA strands whenthe chloro substitution was moved from meta to para position of the phenyl ring. 4-OH derivative showedsimilar affinity to AT and CG-rich DNA strand. Quantum mechanics calculation indicated that 4-OHderivative had the highest HOMO energy. The order in HOMO energies was compatible with the absorptiontitration result that demonstrated the order of Ka as 4-OH>4-Cl>3-Cl.
Synopsis. 5-(benzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione derivatives could interact with ctDNA. MD simulation indicated that m- and p-chlorophenyl derivatives selectively bind to AT and CG-rich DNA strands respectively. The order in HOMO energies was compatible with absorption titration result that demonstrated the order of Ka as 4-OH > 4-Cl > 3-Cl.
Volume 134, 2022
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