# Synthesis and Biological Studies of New 2-Benzoxazolinone Derivatives as Antibacterial Agents
## 1 Introduction  
The global problem of infectious and often fatal diseases caused by Gram-positive and Gram-negative pathogens is currently the main task of scientists, which must be solved as soon as possible. Bacterial infections are generally easier to treat than viral infections because there is a large army of antimicrobial agents that work against bacteria. However, due to the widespread and often excessive use of antibiotics, bacterial resistance to antimicrobial agents is a rapidly growing problem with devastating consequences [1].  
The widespread drug-resistant pathogens such as methicillin-resistant _Staphylococcus aureus_ (MRSA), methicillin-resistant _Staphylococcus epidermidis_ (MRSE), vancomycin-resistant _Staphylococcus aureus_ (VRSA), extended-spectrum \(\beta\)-lactamase (ESBL)-producing _Escherichia coli_, and drug-resistant tuberculosis (DR-TB) have already reached a frightening degree and cause considerable mortality among the world's population [2]. According to the latest estimates of the World Health Organization (WHO), in 2019, 1.27 million deaths were directly attributed to drug-resistant infections worldwide, while by 2050, up to 10 million people in the world can die every year [3]. AMR poses a threat to humans, animals, plants, and the environment. It affects us all.  
To solve this problem, it is necessary not only to raise the level of sanitation and hygiene and awareness of the use of antibiotic substances but also to search for neweffective drugs with the fewest side effects. And this is where the chemistry of heterocycles comes in handy. Among them, benzoxazole pharmacophore, consisting a two fused oxazole and a benzene rings, occupies an important place as a promising target for medicinal chemistry, being a starting material for the synthesis of a number of biological and pharmacological active substances [4] which were found to exhibit antifungal [5; 6], antituberculosis [7; 8], anticancer [9; 10; 11], antileishmanial [12], anti-inflammatory-analgesic [13; 14], and antibacterial [15; 16; 17; 18; 19; 20] properties, and so forth [21; 22; 23; 24; 25; 26]. Benzoxazole scaffolds have had a significant impact on drug discovery, and a variety of benzoxazole-based drugs are market-available nowadays [27; 28; 29]. Among benzoxazoles, the 2(3\(H\))-benzoxazoline derivatives have been described as having diverse applications in medicinal chemistry [30] with large-scale therapeutic activities which include analgesic, anti-inflammatory, antimicrobial [31], cholinesterase inhibitors [32], antinociceptive [33], anti-HIV, antileishmanial, anticancer, antioxidant, antidepressant, and neurodegenerative [34] effects. Some pharmacologically active benzoxazole-2-one derivatives [35; 36; 37; 38; 39] are shown in Figure 1.  
In addition to those mentioned above, synthetic benzoxazoles and their naturally occurring counterparts were found to be biologically active [40; 41] and can be potential materials for drug design. Thus, benzoxazole derivatives are an excellent basis for the search and development of new antimicrobial compounds.  
Considering the above-documented therapeutic efficacy including the broad antimicrobial properties of benzoxazole derivatives and our previous successful studies in the synthesis and discovery of effective antimicrobial agents among azole- and hydrazone-containing compounds [42; 43; 44; 45] led us to the selection of this scaffold and its combinations with hydrazone and azole moieties in the molecules for our further studies. To achieve set goals, a new series of compounds with an integrated benzoxazolin-2-one scaffold were developed to discover the antibacterial potential against _Staphylococcus aureus_, _ Bacillus subtilis_, _Escherichia coli_, and _Salmonella_ Enteritidis pathogens. Notably, the synthesized compounds have shown auspicious antibacterial activity, making them a promising avenue in the search for novel antibacterial pharmaceuticals.