# Novel Adamantane Derivatives: Synthesis, Cytotoxicity and Antimicrobial Properties
## 4 Discussion
### Antimicrobial Activity Assays  
Our research goal was to investigate the effect of the incorporation of the adamantane system into novel Schiff bases and hydrazide-hydrazone compounds. Unfortunately, the combination of adamantane and Schiff bases or a hydrazide-hydrazone moiety did not provide the expected significant enhancement in antibacterial activity against Gram-positive bacterial strains in comparison with previously reported hydrazone compounds [31; 32; 33]. Only selected adamantane derivatives synthesized by our research group were active against all tested Gram-positive bacteria (Schiff bases **9**, **14**, **15** and hydrazide **19**).  
However, the antibacterial activity towards Gram-negative bacterial strains shown by the newly synthesized adamantane derivatives described in this research is not so common in the scientific literature devoted to the antibacterial activity profile of hydrazide-hydrazones [31; 32; 33].  
Although, in the case of antifungal activity, the results were better than expected even though they were much lower than for reference substances. For the activity of hydrazide-hydrazones that were previously reported by our research team, the antifungal activity was moderate, whereas in this research, it is worth underlining, especially compound **5** with a 3-ethoxy-2-hydroxyphenyl substituent, which showed the lowest value of MIC towards _C. albicans_ ATCC 10231 (MIC = 62.5 \(\mu\)g/mL, MBC = 125 \(\mu\)g/mL, MBC/MIC = 2). Other synthesized adamantane derivatives also influence the growth of yeasts from _Candida_ spp.  
According to literature findings, the adamantane derivatives synthesized by [PERSON] et al. [12; 13] and [PERSON] et al. [15], similar to the compounds synthesized by our research group, also displayed interesting activity toward _Candida albicans_ and a few species of Gram-positive bacteria.  
After the analysis of the structure-antibacterial and structure-antifungal activity relationships of the obtained derivatives, it is clear that among hydrazide-hydrazones (**20**-**23**), the substitution of the NH\({}_{2}\) group in hydrazide **19** resulted in a decrease in both antibacterial and antifungal activity. The free amino group of hydrazide **19** promoted activity against Gram-positive bacterial strains. Among Schiff bases (**2**, **3**, **5**-**11**, **13**-**17**), the substitution of the phenyl ring with the electron-withdrawing group--the nitro group at positions 3 (compound **14**) and 4 (compound **9**, **15**)--was the most beneficial substitution for an increase in antibacterial activity. The presence of two electron donating groups in the phenyl ring--two methoxy groups at positions 2 and 3 (compound **2**), 2 and 4 (compound **3**), as well as the adamantanyl (**11**) moiety--decreased the antibacterial potential of the synthesized adamantane derivatives. In the case of antifungal activity, there was no direct connection between the presence of electron-donating or electron-withdrawing groups at the phenyl ring and the bioactivity. The activity increased when in the structure of the Schiff base there was a 3-ethoxy-2-hydroxyphenyl (**5**) or 4-nitrophenyl (**9**) substituent. _Staphylococcus epidermidis_ ATCC 12228 and _Candida albicans_ ATCC 10231 were the most sensitive microorganisms towards tested adamantane derivatives.