Acinetobacter baumannii is resistant to many commercially available antibacterial agents and has become a major threat to the health sector worldwide, resulting in the need to expedite the search for novel and potent antibacterial agents against this bacterium. Eugenol is a natural vanilloid present in the essential oils of Ocimum gratissimum (basil),Cinnamomum verum (cinnamon) and Myristica fragrans (nutmeg) and is also a major component of Syzygium aromaticum (clove) oil. It is used as a dental anaesthetic to relieve pain arising from pulpitis and dentinal hypersensitivity. In addition, it possesses a wide array of biological properties such as antimicrobial, anti-inflammatory, analgesic, anticancer and antidiabetic activities. Due to its broad range of antimicrobial activities, it was targeted as a valuable starting material for the synthesis of derivatives which were hoped to have enhanced antibacterial activity against multidrug resistant (MDR) A.baumannii. Thus, this thesis describes chemical synthesis of new eugenol derivatives and the evaluation of their antibacterial activity against MDR A. baumannii. A total of forty-nine eugenol derivatives were synthesised and characterised using 1H and 13C NMR spectroscopy. Representative clinical isolates of MDR A. baumannii were subjected to challenge by eugenol and its synthesised derivatives via standard antibacterial assays. All the eugenol derivatives exhibited moderate to high antibacterial potencies, with highest potency demonstrated by derivative, E43, 4-allyl-2-methoxyphenyl-2, 4, 6- trichlorobenzoate. In addition, the combined use of E43 with standard antibiotics against MDR A. baumannii yielded additive and synergistic antibacterial effects. In comparing the antibacterial effects of E43 with unmodified eugenol, E43 exhibited 2.3 fold higher potency, followed by E06 with 1.5 fold higher potency and E47 with 1.3 fold higher potency. All the synthesised eugenol derivatives also had greater predicted water solubility than unmodified eugenol and predicted cardio and neuro toxicities were within the acceptable range. Thus, these novel synthesised eugenol derivatives have immense potential for development into efficacious anti MDR A. baumannii drugs. The introductionof such drugs into the commercial market today would be a timely solution towards combating recalcitrant MDR A. baumannii infections, thereby significantly reducing associated morbidity, disability-adjusted life years (DALY) and mortality. The focus of research then pivoted towards investigating the underlying mechanism of antibacterial activity exhibited by E43. Could E43 be down regulating the efflux pumps of MDR A. baumannii? The efflux pump genes adeB, adeR and adeS of the RND efflux system, AdeABC, of MDR A. baumannii, were subsequently detected by PCR. Using RTqPCR, all three of these efflux genes were found to be significantly down – regulated in E43 treated MDR A. baumannii in comparison to untreated controls, suggesting that the additive and synergistic effects between E43 and the antibiotics was due to the down regulation in A. baumannii by E43 of this major efflux system. However, the latter findings did not explain how E43 could kill MDR A. baumannii when acting on its own. In silico studies performed using the Schrodinger small-molecule drug discovery suite 2019-2 were strongly suggestive that E43 directly interacts and binds the A. baumannii class D carbapenemase, A. baumannii outer membrane carboxylate channel porin protein, OccAB3 and the A. baumannii AdeB protein, possibly causing dysfunctionalisation of these proteins. Thus, the E43 mode of action in killing MDR A. baumannii seems to bemulti-pronged, inhibiting expression of AdeB well as, by direct binding to the protein, possibly detrimentally affecting its functionality. In addition, E43 possibly binds andrenders the class D carbapenemase of MDR. A. baumannii dysfunctional, thereby facilitating lethal effects on the bacterium in the presence of carbapenem antibiotics. Possible binding of the porin protein, OccAB3, by E43 may have modified the selectivity of this porin leading to reduced uptake of its regular amino – acid substrates, such as glycine and glutamic acid. Impediment of amino – acid uptake by E43 binding to this porin may have contributed to amino – acid starvation and its lethal effects on MDR A. baumannii when used alone. In conclusion, this study has confirmed that eugenol derivative E43 is highly biologically active in killing MDR A. baumannii. Mechanistic studies have demonstrated that this compound kills via inhibition of the AdeABC efflux pump with likely pleiotropic effects on bacterial viability.