# Flavone Hybrids and Derivatives as Bioactive Agents
## 2 Flavone Hybrids with Different Pharmacophores
### Hybrids with 1,2,3-Trizzoles and Their Derivatives
\begin{table}
\begin{tabular}{c c c c c c c} \hline
**Flavone** & **Pharmacophore** & **Biological Effect** & **Activity \({}^{*}\)** & **Control Activity** & **Section** & **Reference** \\ \hline chrysin & amino acids & antiproliferative & \(IC_{50}=3.78\) uM & cisplatin, & & & \\  & & & (MGC-803) & \(IC_{50}=4.40\) uM & 2.3. & [21, 22] \\ \hline quercetin & amino acids & MDR modulator & \(IC_{50}=0.14\) uM & doxorubicin, & & & \\  & & & (MES-SA/Dr\(\Sigma\)5) & \(IC_{50}=8.20\) uM & 2.3. & [23] \\ \hline
2-phenylchromen- & \multirow{2}{*}{amino acids} & antiproliferative & \(IC_{50}=9.2\) uM & & & & \\
4-one & & & (CCRF-CEM) & n.d. & 2.3. & [24] \\ \hline chrysin & vindoline & antiproliferative & \(GI_{50}=1.1\) uM & & & & \\  & & & (COX M/V) & n.d. & 2.4. & [12] \\ \hline chrysin & morpholine & antibacterial & \(\text{MIC}=6.25\) u/mL & streptomycin, & & & \\  & & & (_B. spinerics_) & MIC = 125 u/mL & 2.5. & [25] \\ \hline chrysin & piperazines & antitumor & \(IC_{50}=4.67\) uM & gefitinib, & & & \\  & & & (HeLa) & \(IC_{50}=17.9\) uM & 2.5. & [26] \\ \hline apigenin & piperazines & antitumor & \(IC_{50}=0.0147\) uM & olaparib, & & & \\  & & & (PARP-1 inhibition) & \(IC_{50}=0.0051\) uM & 2.5. & [27] \\ \hline
2-phenylchromen- & imidazole[1,2-a] & antiplasmodal & \(IC_{50}=1.98\) uM & chloroquine, & & & \\
4-one & pyridine & & (_P. falciparum_ K1) & \(IC_{50}=0.25\) uM & 2.6. & [28] \\ \hline
2-phenylchromen- & \multirow{2}{*}{2-amino-thiazole} & \multirow{2}{*}{antibacterial} & \(\text{MIC}=12.5\) u/mL & ciprofloxacin, & & \\  & & & (_B. limits_) & MIC \(<1.5\) ug/mL & 2.6. & [29] \\ \hline
7-hydroxflavone &
\begin{tabular}{c} dihydro-1H- \\ furo[2,3- \\ clpyrazole \\ \end{tabular} & antitumor & \(IC_{50}=2.5\) uM & doxorubicin, & & & \\  & & (Hep2) & \(IC_{50}=10\) uM & 2.6. & [30] \\ \hline
7-hydroxflavone & \multirow{2}{*}{acridine} & monoamine & \(IC_{50}=3.24\) uM & tacrine, & & \\  & & oxidase inhibitor & (MAO-B inhibition) & \(IC_{50}=7.85\) uM & 2.6. & [31] \\ \hline
5,6,7-trimethoxy- & \multirow{2}{*}{6-chlorotetcine} & anti-Alzheimer’s disease & \(IC_{50}=0.0128\) uM & 6-chlorotetcine, & & \\  & & & (AChE inhibition) & \(IC_{50}=0.0785\) uM & 2.6. & [32] \\ \hline chrysin & apigenin & antiproliferative & \(IC_{50}=0.179\) uM & olaparib, & & & \\  & & (PARP-1 inhibition) & \(IC_{50}=0.0051\) uM & 2.7. & [27] \\ \hline mosolfavone & resveratrol & anti-inflammatory & \(IC_{50}=0.31\) uM & & & \\  & & & (PGE\({}_{2}\) inhibition) & n.d. & 2.8. & [33] \\ \hline
2-phenylchromen- & \multirow{2}{*}{naphthopyran} & xanthine & \(IC_{50}=0.62\) uM & apigenin, & & \\
4-one & & oxidase inhibitor & (XO inhibition) & \(IC_{50}=1.11\) uM & 2.9. & [34] \\ \hline
2-phenylchromen- & \multirow{2}{*}{estradiol} & antiproliferative & \(IC_{50}=3.9\) uM & cisplatin, & & \\  & & & (HeLa) & \(IC_{50}\geq 330\) uM & 2.9. & [35] \\ \hline kaempfer & carbohydrate & antibacterial & \(\text{MIC}=0.05\) ug/mL & ciprofloxacin, & & \\  & & & (_S. gallium_) & MIC = 0.25 ug/mL & 2.9. & [36] \\ \hline \end{tabular}  
* \({}^{*}\) The activities presented are the value of the most effective derivative. The type of microorganism or cell line tested is shown in parentheses.  
\end{table} 
Table 1: _Cont._Thus, chrysin was reacted with propargyl bromide, and the propargyl derivative was subjected to a click reaction with various benzyl azide derivatives (prepared in situ) [14], resulting in the chrysin hybrids coupled with the pharmacophore in position 7. The antibacterial activity of the new compounds was investigated on 3-3 Gram-positive and Gram-negative pathogenic bacteria strains, respectively. Most of the derivatives showed moderate-to-excellent antibacterial effects. Then, it was pointed out [15] that compound **5** (R=F, NO\({}_{2}\)) and its dimer derivative (**6**) (Figure 4) have moderate antiproliferative activity on several cell lines of different types of cancer. Among these, compound **6** (R=F) is the most important, with an \(IC_{50}\) = 0.73 \(\upmu\)M activity on HeLa cells.