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CDFT-based chemical reactivity properties analysis of the fluorine substitution in the selective estrogen receptor modulator (SERM) Tamoxifen

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Abstract

In Mexico, breast cancer is the leading cause of cancer death among women. The growing increase in the disease is closely related to the aging of the population and a higher prevalence of risk factors among the female population. Currently, breast cancer is one of the main health problems for women over 40 years of age. Conventional cancer therapies face significant challenges such as poor bioavailability and intrinsic toxicity. The replacement of a carbon–hydrogen and carbon–oxygen bond with a carbon–fluorine bond in medicinally active compounds has often been found to introduce or improve desirable pharmacological properties, such as higher metabolic stability. Fluorine imparts desirable characteristics to the drug modulating both the pharmacokinetics and pharmacodynamics properties. There are many examples of the use of fluorine to modify physical properties, binding characteristics, and metabolic disposition. Molecular Modeling techniques can predict the properties and behavior of new drugs. In this work, the modification of Tamoxifen’s structures, which belong to the family of selective estrogen receptor modulators (SERMs) used against breast cancer, was done by including fluorine (F) atoms replacing the hydrogen (H) ones in specific sites defined by the computational calculations’ progress. The new drugs were studied by determining their molecular structures and properties by considering Density Functional Theory (DFT) and calculating the parameters associated with chemical reactivity by resorting to Conceptual DFT. In a complementary way, the pharmacokinetics and bioavailability of the newly generated molecules were established using some commonly available Cheminformatics tools.

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Acknowledgements

Daniel Glossman-Mitnik (DGM) and Norma Flores-Holguín (NFH) are researchers at CIMAV and CONACYT from which partial support is also acknowledged.

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This work received no external funding.

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Author notes

  1. Norma Flores-Holguín and Daniel Glossman-Mitnik have contributed equally to this work.

Authors and Affiliations

  1. Laboratorio Virtual NANOCOSMOS - Departamento de Medio Ambiente y Energía, Centro de Investigación en Materiales Avanzados, Miguel de Cervantes 120, 31136, Chihuahua, Chihuahua, Mexico

    Norma Flores-Holguín & Daniel Glossman-Mitnik

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  1. Norma Flores-Holguín
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NFH conceived the concept and designed the study. NFH and DGM carried out the theoretical calculations and analysis. NFH and DGM co-wrote the paper. All authors discussed the results and commented on the manuscript.

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Correspondence to Norma Flores-Holguín.

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Flores-Holguín, N., Glossman-Mitnik, D. CDFT-based chemical reactivity properties analysis of the fluorine substitution in the selective estrogen receptor modulator (SERM) Tamoxifen. Theor Chem Acc 142, 79 (2023). https://doi.org/10.1007/s00214-023-03018-4

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