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    • Effect of substitution on the binding affinity of 5- bezylidenebarbituric acid derivatives to ctDNA: in silico and in vitro studies

      DARA DASTAN AHMAD EBADI

      Volume 134 Published: 2 February 2022 Article ID 0020

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      Permanent link:
      https://www.ias.ac.in/article/fulltext/jcsc/134/0020

    • Keywords

       

      Cancer; 5-bezylidenebarbituric acid; ctDNA; spectrophotometric titration; quantum mechanics; MD simulation.

    • Abstract

       

      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.

    • Graphical Abstract

       

      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.

    • Author Affiliations

       

      DARA DASTAN1 AHMAD EBADI2

      1. Department of Pharmacognosy, School of Pharmacy, Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
      2. Department of Medicinal Chemistry, School of Pharmacy, Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

    • Dates

       
      Published
      2 February 2022
      Manuscript received
      19 June 2021
      Manuscript revised
      21 September 2021
      Accepted
      30 September 2021

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