2. Academic Validation
  3. Quantitative relationships between structure and cytotoxic activity of flavonoid derivatives. An application of Hirshfeld surface derived descriptors

Quantitative relationships between structure and cytotoxic activity of flavonoid derivatives. An application of Hirshfeld surface derived descriptors

  • Bioorg Med Chem Lett. 2016 Jul 15;26(14):3336-3341. doi: 10.1016/j.bmcl.2016.05.038.
Bogumiła Kupcewicz 1,  Magdalena Małecka 2,  Mariusz Zapadka 3,  Urszula Krajewska 4,  Marek Rozalski 4,  Elzbieta Budzisz 5
Affiliations

Affiliations

  • 1 Department of Inorganic and Analytical Chemistry, Ludwik Rygygier Collegium Medicum, Nicolaus Copernicus University in Torun, Jurasza 2, 85-089 Bydgoszcz, Poland. Electronic address: kupcewicz@cm.umk.pl.
  • 2 Department of Theoretical and Structural Chemistry, Faculty of Chemistry, University of Lodz, Pomorska 163/165, 90-236 Lodz, Poland.
  • 3 Department of Inorganic and Analytical Chemistry, Ludwik Rygygier Collegium Medicum, Nicolaus Copernicus University in Torun, Jurasza 2, 85-089 Bydgoszcz, Poland.
  • 4 Department of Pharmaceutical Biochemistry, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland.
  • 5 Department of Cosmetic Raw Materials Chemistry, Faculty of Pharmacy, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland.
PMID: 27234147 DOI: 10.1016/j.bmcl.2016.05.038
Abstract

Quantitative relationships between the structure and cytotoxic activity of series flavonoid derivatives were examined. The first regression-based model, developed for 18 flavanone-2-pyrazoline hybrids, involved two interpretable descriptors: a Mor04v and partial atomic charge. The second model, developed for structurally diverse set of compounds, was based on descriptors derived from Hirshfeld surface analysis. This model suggests that cytotoxic activity of compounds can be successfully predicted based on a fraction of H⋯H contacts and a fraction of interactions involving a halogen atom. For non-halogen derivatives, the data reveal that cytotoxic activity is inversely proportional to the percentage of O⋯H and N⋯H close contacts to Hirshfeld surface, while directly proportional to the percentage of H⋯H interactions. Chlorine (1k) and bromine (1l) derivatives of compounds, containing flavanone fused with N-methyl-2-pyrazoline, exhibited high cytotoxic potential against HL-60 Cancer cell line (IC50<10μM). The cytotoxicity of 1k and 1l towards normal cells (HUVEC) was 10 and 25-fold lower, respectively.

Keywords

Cytotoxicity; Flavonoid derivatives; Hirshfeld surface; Pyrazoline; QSAR.

Figures