## 4 Conclusions  
Hydroxylated chalcone/flavanone derivatives were synthesized using the less common bases NaH or LiHMDS. Overall, it was shown that the use of NaH is efficient (-80% yield in 3-4 h) for the synthesis of chalcones not hydroxylated other than at C-2' position. However, if the desired derivatives are polyhydroxylated chalcones, the use of LiHMDS is preferable, because the conversion rate is good and it is a one-pot procedure that avoids the protection and subsequent deprotection steps, a time-consuming procedure that also significantly decreases the total yield. Although the aim of this work was to obtain the compounds for biological evaluation, we suggest microwave or ultrasound irradiation as a better source of energy to increase the compounds' yields, an aspect that is important for their future applications. Figure 7: Structure/activity relationships established for antitumor activity. \begin{table}
\begin{tabular}{c c} \hline \hline \multirow{2}{*}{**Compounds and References**} & **IC\({}_{50}\)\(\mu\)g/mL (\(\pm\) SD)** \\ \cline{2-3}  & **A549 Cell Line** \\ \hline
**1** & 101.23 (\(\pm\)0.42) \({}^{\mathrm{a}}\) \\
**4** & 135.89 (\(\pm\)2.61) \({}^{\mathrm{b}}\) \\
**5** & 93.42 (\(\pm\)2.42) \({}^{\mathrm{c}}\) \\
**6** & \(>\)200 \\
**7** & \(>\)200 \\
**8** & 93.31 (\(\pm\)2.45) \({}^{\mathrm{c}}\) \\ Paclitaxel & 5.96 (\(\pm\)0.48) \({}^{\mathrm{d}}\) \\ Colchicine & 2.78 (\(\pm\)0.71) \({}^{\mathrm{d}}\) \\ \hline \hline \end{tabular} In each column the letters a, b, c, d, and e indicate significant differences (\(p<0.05\)).  
\end{table} 
Table 3: Antitumor activity of the synthesized compounds **1**, **4**–**8**. Some of the compounds synthesized presented interesting results in their bioactivities, with chalcone **6** being the most active compound in terms of antioxidant, anti-butyrylcholinesteraseerase and antimicrobial activity. Its isomer, flavanone **7**, showed activity against both acetylcholinesterase and butyrylcholinesteraseerase, which is an interesting result since this dual inhibition is a much-appreciated feature in [PERSON]'s disease therapy. Also, it is interesting that these compounds can be obtained in the one-pot methodology using LiHMDS. Some important structure/activity relationships were established for all the activities tested, and the most important are highlighted and summarized in Figure 8.  
As shown in Figure 8, the free hydroxyl groups are essential to increase antioxidant, anti-butyrylcholinesteraseerase and antimicrobial activities. Not only their presence but also their number increases the compounds' activity, while methoxyl groups decrease it. The flavanone scaffold increases the acetylcholinesterase mobilesterase inhibitory activity, while for the butyrylcholinesteraseerase inhibition, the chalcone scaffold appears to be better. This is another interesting result because it is known that these compounds are isomers, and in biological systems they can exist in a controlled equilibrium. Regarding the antimicrobial activity, it is possible to detect that the cyclization into flavanone has no effect against the _M. luteus_ strain, whereas against _B. subtilis_, the flavanone decreases the antibacterial activity. So, it seems that the \(\alpha\),\(\beta\) unsaturated carbonyl bridge linking rings A and B is important to inhibit the growth of the _B. subtilis_ strain. Finally, it can be established that the presence of methoxyl groups in both chalcones and flavanones increases the antitumor activity.