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

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Abstract

Cancer is the second leading cause of death worldwide. Drug researchers have encouraged by the growth of cancer incidence and low efficacy of current treatment to discover new drugs. Targeting specific regions of DNA to turn on/off genes has become an interesting research area. We evaluated the interaction of 5-(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 when the chloro substitution was moved from meta to para position of the phenyl ring. 4-OH derivative showed similar affinity to AT and CG-rich DNA strand. Quantum mechanics calculation indicated that 4-OH derivative had the highest HOMO energy. The order in HOMO energies was compatible with the absorption titration result that demonstrated the order of Ka as 4-OH > 4-Cl > 3-Cl.

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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.

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Acknowledgements

We are grateful to the Vice-chancellor for Research and Technology, Hamadan University of Medical Sciences for financial support of this work (No. 9504222158).

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Authors and Affiliations

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

    Dara Dastan

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

    Ahmad Ebadi

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  1. Dara Dastan
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  2. Ahmad Ebadi
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Correspondence to Ahmad Ebadi.

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Dastan, D., Ebadi, A. Effect of substitution on the binding affinity of 5-bezylidenebarbituric acid derivatives to ctDNA: in silico and in vitro studies. J Chem Sci 134, 20 (2022). https://doi.org/10.1007/s12039-021-02007-z

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  • DOI: https://doi.org/10.1007/s12039-021-02007-z

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