# Novel Adamantane Derivatives: Synthesis, Cytotoxicity and Antimicrobial Properties
## 1 Introduction  
Adamantane is an organic chemical compound belonging to polycyclic hydrocarbons. According to the review of the scientific literature, it can be stated that searching for new adamantane derivatives is currently a course of research adopted by many research groups around the world. The main reason for this state of affairs is the documented biological activity of many derivatives of this compound [1]. It is also very important that the introduction of the adamantane system to novel compounds usually results in an increase in lipophilicity. In turn, this may modify the bioavailability of synthesized substances and enlarge their therapeutic effect [1].  
Adamantane derivatives display significant biological activity, including antiviral [1; 2; 3; 4; 5; 6], antidiabetic [1; 7; 8; 9; 10; 11], antibacterial [1; 12; 13; 14; 15], antimalarial [1; 16; 17], anticancer [1; 18; 19; 20; 21] activities and anti-inflammatory properties [1; 22; 23].  
Many currently used drugs contain the adamantane system. Amantadine, rimantadine and tromantdine are examples of amine derivatives of adamantane with antiviral activity (Figure 1). Some adamantane derivatives, like vildagliptin or saxagliptin, show antidiabetic activity and are used to treat type 2 diabetes mellitus (T2 DM) (Figure 2), whereas adapalene is known for its anti-inflammatory activity, and it is used in the treatment of acne (Figure 3) [1; 11; 22].  
In recent years, scientists have also paid attention to the antimicrobial properties of adamantane derivatives [1] since bacterial resistance to commonly used antibacterial agents is rising, making the treatment of infections much more challenging than before [24; 25].  
[PERSON] et al. [14] synthesized interesting derivatives of isothiurea that contained the adamantane system. The obtained compounds showed significant antibacterial activity towards Gram-positive and Gram-negative bacteria. Additionally, synthesized derivatives highly decreased glucose levels in blood serum in comparison to gliclazide [14]. [PERSON] et al. [15] obtained novel hydrazide-hydrazones with the 1-adamantane carbonyl moiety and tested the synthesized substances on some Gram-negative and Gram-positive bacteria, as well as the fungus _Candida albicans_. The screening results revealed that four compounds possess good antibacterial properties against Gram-positive bacteria and _C. albicans_ in comparison with known antimicrobial reference substances [15]. According to the latest research, derivatives of adamantane are reported to also influence the biofilm formation of _E. faecalis_, _P. aeruginosa_ and methicillin-resistant _S. aureus_, and their antimicrobial activity may be attributed to membranotropic activity [26; 27; 28].  
For many years now, our research team has focused on the synthesis of novel compounds with a hydrazide-hydrazone moiety that display significant antimicrobial and anticancer activity [29; 30]. According to our previous studies, hydrazide-hydrazones are promising antibacterial agents, especially against Gram-positive bacterial strains, and antifungal against the yeasts from _Candida_ spp. [31; 32; 33].  
Based on the facts presented above, which point to the interesting and broad biological activity of adamantane derivatives, we decided to synthesize novel Schiff bases and hydrazide-hydrazones containing the adamantane system and then establish their in vitro antimicrobial activity and test their cytotoxicity. Our goal was to investigate whether the connection of the adamantane system with a Schiff base or hydrazide-hydrazone moiety  
Figure 1: Amine derivatives of adamantane with antiviral activity.  
Figure 3: Chemical structure of adapalene.  
Figure 2: Adamantane derivatives with antidiabetic activity.  
would enhance or decrease its antibacterial and antifungal activity in comparison with our previously obtained results for other compounds from the same group.