Quantitative relationships between structure and cytotoxic activity of flavonoid derivatives. An application of Hirshfeld surface derived descriptors. Issue 14 (15th July 2016)

• Record Type: Journal Article
• Authors: Kupcewicz, Bogumiła; Małecka, Magdalena; Zapadka, Mariusz; Krajewska, Urszula; Rozalski, Marek; Budzisz, Elzbieta
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 14(2016)
• Page Start: 3336
• Page End: 3341
• Publication Date: 2016-07-15
• Subjects: QSAR -- Hirshfeld surface -- Cytotoxicity -- Flavonoid derivatives -- Pyrazoline; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.05.038
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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 < 10 μM). The cytotoxicity of1k and1l towards normal cells (HUVEC) was 10 and 25-fold lower, respectively.