TY - JOUR
T1 - Novel quercetin and apigenin-acetamide derivatives
T2 - Design, synthesis, characterization, biological evaluation and molecular docking studies
AU - Isika, Daniel
AU - Çeşme, Mustafa
AU - Osonga, Francis J.
AU - Sadik, Omowunmi A.
N1 - Publisher Copyright:
© The Royal Society of Chemistry.
PY - 2020/6/30
Y1 - 2020/6/30
N2 - Flavonoids exhibit essential but limited biological properties which can be enhanced through chemical modifications. In this study, we designed, synthesized, and characterized two novel flavonoid derivatives, quercetin penta-acetamide (1S3) and apigenin tri-acetamide (2S3). These compounds were confirmed using (1H, 13C) NMR, UV-Vis, and FT-IR characterizations. Their interaction with fish sperm DNA (FS-DNA) at physiological pH was investigated by UV-Vis and fluorescence spectrophotometry. The binding constant (Kb) for the UV-Vis experiment was found to be 1.43 ± 0.3 × 104 M-1 for 1S3 and 2.08 ± 0.2 × 104 M-1 for 2S3. The binding constants (KSV) for the fluorescence quenching experiment were 1.83 × 104 M-1 and 1.96 × 104 M-1 for 1S3 and 2S3, respectively. Based on molecular modeling and docking studies, the binding affinities were found to be -7.9 and -9.1 kcal mol-1, for 1S3 and 2S3, respectively. The compound-DNA docked model correlated with our experimental results, and they are groove binders. Furthermore, mutagenicity potential was examined. 1S3 and its metabolites showed no mutagenic activity for both TA98 and TA100 strains. 2S3 did not show any mutagenic activity for the strain TA 98, while its metabolites were only active at high doses. Both 2S3 and its metabolites showed mutagenic activity in the TA100 strain.
AB - Flavonoids exhibit essential but limited biological properties which can be enhanced through chemical modifications. In this study, we designed, synthesized, and characterized two novel flavonoid derivatives, quercetin penta-acetamide (1S3) and apigenin tri-acetamide (2S3). These compounds were confirmed using (1H, 13C) NMR, UV-Vis, and FT-IR characterizations. Their interaction with fish sperm DNA (FS-DNA) at physiological pH was investigated by UV-Vis and fluorescence spectrophotometry. The binding constant (Kb) for the UV-Vis experiment was found to be 1.43 ± 0.3 × 104 M-1 for 1S3 and 2.08 ± 0.2 × 104 M-1 for 2S3. The binding constants (KSV) for the fluorescence quenching experiment were 1.83 × 104 M-1 and 1.96 × 104 M-1 for 1S3 and 2S3, respectively. Based on molecular modeling and docking studies, the binding affinities were found to be -7.9 and -9.1 kcal mol-1, for 1S3 and 2S3, respectively. The compound-DNA docked model correlated with our experimental results, and they are groove binders. Furthermore, mutagenicity potential was examined. 1S3 and its metabolites showed no mutagenic activity for both TA98 and TA100 strains. 2S3 did not show any mutagenic activity for the strain TA 98, while its metabolites were only active at high doses. Both 2S3 and its metabolites showed mutagenic activity in the TA100 strain.
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U2 - 10.1039/d0ra04559d
DO - 10.1039/d0ra04559d
M3 - Article
AN - SCOPUS:85087697117
SN - 2046-2069
VL - 10
SP - 25046
EP - 25058
JO - RSC Advances
JF - RSC Advances
IS - 42
ER -