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

In this study, four novel naphthoquinone–thiazole hybrids bearing adamantane were synthesized byreaction of naphthoquinone–aroylthiourea derivatives with 1-adamantyl bromomethyl ketone in 75-85% yield and werecharacterized using 1H/13C NMR, FT-IR, and HRMS techniques. Various biological activities of the synthesizedcompounds, such as antibacterial, antifungal, DNA cleavage, and antioxidant activities, were screened. The compoundsshowed 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 μg/mLand antifungal activity against Candida albicans strains with MIC values in the range of 16–64 μg/mL. The compoundshad DNA cleavage activity at 250 and 500 μg/mL. Additionally, the antioxidant activity of the compounds was assessedbased on the radical scavenging effect of the stable DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical and thecompounds exhibited acceptable antioxidant activity. The acid dissociation constants (pKa) of the compounds weredetermined potentiometrically in 30% (v/v) dimethyl sulfoxide–water at an ionic background of 0.1 mol L-1 NaCl, at 25± 0.1 °C, and the HYPERQUAD computer program was used to calculate the pKa values from the data obtained frompotentiometric titrations. Prediction of the drug-likeness properties of the compounds was performed with the use ofthe MolSoft website, and the compounds had promising drug-likeness model scores within a range of 1.09–1.56.

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