Naphthoquinone-thiazole hybrids bearing adamantane: Synthesis, antimicrobial, DNA cleavage, antioxidant activity, acid dissociation constant, and drug-likeness


DOĞAN A. , ÖZDEMİR S., Yalcin M. S. , SARI H., NURAL Y.

JOURNAL OF RESEARCH IN PHARMACY, vol.25, no.3, pp.292-304, 2021 (Journal Indexed in ESCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 25 Issue: 3
  • Publication Date: 2021
  • Doi Number: 10.29228/jrp.20
  • Title of Journal : JOURNAL OF RESEARCH IN PHARMACY
  • Page Numbers: pp.292-304

Abstract

In this study, four novel naphthoquinone-thiazole hybrids bearing adamantane were synthesized by reaction of naphthoquinone-aroylthiourea derivatives with 1-adamantyl bromomethyl ketone in 75-85% yield and were characterized using H-1/C-13 NMR, FT-IR, and HRMS techniques. Various biological activities of the synthesized compounds, such as antibacterial, antifungal, DNA cleavage, and antioxidant activities, were screened. The compounds showed antibacterial activity against Escherichia coli, Bacillus cereus, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus hirae, and Legionella pneumophila subsp. pneumophila strains with MIC values in the range of 4-64 mu g/mL and antifungal activity against Candida albicans strains with MIC values in the range of 16-64 mu g/mL. The compounds had DNA cleavage activity at 250 and 500 mu g/mL. Additionally, the antioxidant activity of the compounds was assessed based on the radical scavenging effect of the stable DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical and the compounds exhibited acceptable antioxidant activity. The acid dissociation constants (pK(a)) of the compounds were determined potentiometrically in 30% (v/v) dimethyl sulfoxide-water at an ionic background of 0.1 mol L-1 NaCl, at 25 +/- 0.1 degrees C, and the HYPERQUAD computer program was used to calculate the pKa values from the data obtained from potentiometric titrations. Prediction of the drug-likeness properties of the compounds was performed with the use of the MolSoft website, and the compounds had promising drug-likeness model scores within a range of 1.09-1.56.