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Theoretical study of anticancer properties of indolyl-oxazole drugs and their interactions with DNA base pairs in gas phase and solvent

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Abstract

In this study, the anticancer properties of a series of synthesized indolyl-oxazoles drugs 1–6 and their interactions with DNA base pairs were investigated. The quantum molecular descriptors (chemical potential, hardness, and electrophilicity) for studied drugs and their complexes with DNA base pairs were calculated. The reaction enthalpies (BDE and IP) of HAT and SET-PT mechanism of anticancer action of drugs 1–6 were calculated. Results reveal that interactions of indolyl-oxazole drugs with DNA base pairs are energetically favorable and solvent increase the binding energies in comparison with gas phase. The binding energies of drugs 4–6 DNA base pairs complexes are more negative than corresponding values for drugs 1–3. The obtained binding energy and reaction enthalpy (BDE and IP) trends for drugs 1–6 confirm pervious experimental anticancer activity trends. IC50 scale has been used as a benchmark for measuring the anticancer activity. Based on theoretical and published experimental scales, drugs 4, 5, and 6 have higher anticancer activity among drugs 1–6. Finally, according to the obtained results, drugs 7–10 can consider as novel drugs with higher anticancer activity than drug 1. Results show that binding energies of drugs 7–10 with DNA base pairs were more negative than corresponding values for drugs 1–6. The BDE and IP values of drugs 4–10 were lower than corresponding values of drug 1. For drugs 1–10, results indicated that the SET-PT and HAT mechanisms represent the thermodynamically preferred mechanism in solvent and gas phase, respectively.

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Abbreviations

DFT:

Density functional theory

PW91:

Perdew–Wang 91

COSMO:

Conductor like screening model

B3LYP:

Becke, 3-parameter, Lee–Yang–Parr

DNA:

Deoxyribonucleic acid

WC:

Watson–Crick

A:

Adenine

T:

Thymine

G:

Guanine

C:

Cytosine

HB:

Hydrogen bond

E b :

Binding energy

BDE:

Bond dissociation enthalpy

IP:

Ionization potential

SET-PT:

Single electron transfer followed by proton transfer

HAT:

Hydrogen atom transfer

µ :

Chemical potential

η :

Hardness

ω :

Electrophilicity

HOMO:

Highest occupied molecular orbital

LUMO:

Lowest unoccupied molecular orbital

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Acknowledgments

We gratefully acknowledge the support of the University of Mazandaran for research facilities.

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  1. Department of Physical Chemistry, Faculty of Chemistry, University of Mazandaran, 47416-95447, Babolsar, Islamic Republic of Iran

    Davood Farmanzadeh & Meysam Najafi

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  1. Davood Farmanzadeh
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Correspondence to Davood Farmanzadeh.

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Farmanzadeh, D., Najafi, M. Theoretical study of anticancer properties of indolyl-oxazole drugs and their interactions with DNA base pairs in gas phase and solvent. Struct Chem 26, 831–844 (2015). https://doi.org/10.1007/s11224-014-0546-8

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