Introduction: Urinary tract infections are among the most common infectious diseases worldwide, causing approximately 150 million cases each year, but they remain understudied (Murray BO et al.,2021). Urinary tract infection (UTI) is an inflammatory condition caused by the presence and growth of microorganisms anywhere in the urinary tract. This may be a lower urinary tract infection (urethritis, cystitis) and/or an upper urinary tract infection (Johnson B et al.,2021). Urinary tract infections place an immediate burden on the patient, including physical and emotional distress, as well as the risk of bacteremia and sepsis. For many patients, discomfort and the risk of urinary tract infections become recurring problems. About 1 in 4 young patients will have recurrent UTIs within 6 months of the first episode, and the risk of recurrence is greatly increased in those who have had multiple episodes(Langford BJ et al.,2021). 2-Hydroxybenzoic or salicylic acid (SA), recognized in 1992 as the sixth plant hormone, belongs to the family of natural phenolic compounds having an aromatic benzene ring with one or more hydroxyl groups (Bagautdinova ZZ et al.,2022). Among species, salicylic acid (SA) is widely distributed throughout the plant kingdom. The basic level of SA is different. It usually exists as a free fraction or as glycosylated, methylated compounds, glucose esters or amino acids ) Janda T et al.,2020). It is a polyhydroxyflavonol compound consisting of pale yellow crystals and is easily soluble in methanol, acetonitrile, ethanol and other polar solvents (Song X et al.,2021). The structure of myristin is related to the structures of many other phenolic compounds such as quercetin, murine, kaempferol and fistin. Due to structural similarities, myristin is also known as hydroxyquercetin (Imran M et al.,2021). Quercetin, a name derived from quercetum (oak forest), has been in use since 1857. The name occurs widely in natural plants, including apples, berries, Brassica vegetables, capers , grapes, onions, green onions, tea and tomatoes. as well as in many seeds, nuts, flowers, bark and leaves (Yang D et al.,2020). Salicin is one of the natural compounds extracted from plants. Salicin is the precursor to the synthesis of salicylic acid and aspirin with undeniable anti-inflammatory effects(Saracila M et al.,2023). Rutin, also known as rutoside, rutinum, vitamin P, quercetin-3-O-rutinoside and sophorin, is found in many plants such as tea, buckwheat, tobacco and citrus fruits(Siti HN et al.,2020). Isoramantine is a plant-derived secondary metabolite that belongs to the family of flavonoids and specifically to the group of flavonols. Flavonoids are a large group of bioactive phytochemicals consisting of two phenolic benzene rings and one heterocyclic ring) González-Arceo M et al.,2022). Flavonols are the most common flavonoid chemical structure and are present in approximately two-thirds of the diets of Western societies. They are responsible for the color and flavor of food, prevent the oxidation of fats, and protect vitamins and enzymes. Examples of these flavonoids are kaempferol, quercetin, myristicin and isoramantin) Silva dos Santos J et al.,2021).
Methods: In this research, the Hdock server was used to perform molecular docking. For this purpose, the ligand and protein files were uploaded on the website and the result of docking was observed. In this research, compounds with medicinal properties were investigated. The structures of the desired compounds were obtained from http://pubchem.ncbi.nlm.nih.gov. Names and structural details of studied compounds are given in Table 1. The appropriate crystal structure of the enzyme containing the central catalytic part was selected and downloaded from http://www.rcsb.org/pdb. Enzyme code on this site is 2zmx with 1/33 angstrom resolution.Preparation of ligand and protein tyrosinase for docking: The two-dimensional structure of the desired ligands was drawn by the Hyperchem program and then optimized in terms of energy by the same software. In the next step, the extra structures of the enzyme, including water and non-protein parts, were removed using Discovery software, and after that, it was fully optimized and prepared for molecular docking by Chimera program. The studied protein file and ligand file were uploaded and submitted in the HDock server. In the next step, the top 10 molecular docking models were downloaded and the model with the most negative binding energy was fully investigated.Observation and analysis of docking results: after performing the docking operation, the results include Most favored regions and Disallowed regions, binding energy of ligands, types of ligand interactions with protein including hydrogen interactions, hydrophobic interactions, types of pi number interactions, interactions with ions Copper in the active site of the enzyme and other things can be seen and analyzed. In order to obtain the mentioned information, Discovery software and two Pdb Sum Generate, HDock servers were used.
Results: In inhibiting the Esbl enzyme, the energy level of the compounds that have formed hydrogen bonds in the active site of the enzyme are as follows: salicylic acid-94/42, myristicin-172/70, kaempferol-167/89, quercetin-175/58, salicin-29 149/149, rutin-77/93, luteonin-54/165, visuramentin-185.
Conclusion: Flavonols are the most common flavonoid chemical structure and are present in approximately two-thirds of the diets of Western societies. They are responsible for the color and flavor of food, prevent the oxidation of fats, and protect vitamins and enzymes. Examples of these flavonoids are kaempferol, quercetin, myristicin and isoramantin. . In a study conducted by Kullappan Malathi et al. in 2018 on bioinformatics methods to discover new drugs and compounds OxA_10 ESBL and imipenem establish hydrogen bonds with phe208, ser67, Glu244 and Arg250 in the active site of the enzyme.Additionally, in a study conducted by Mahmoud A et al. in 2020, for the isolation and bioassay-guided linkage of potential beta-lactamase inhibitors from Clutia myricoides, their 1, 2 and 3 combinations with thr235, ser237, ser70, Asn104 and Asn132 in the active site of the enzyme was established as a hydrogen bond. while salicylic acid, myristin, kaempferol, quercetin, isoramentin, luteonin with ser70 and Asn132, and salicin with ser237 and rutin with ser70 in the active site of the enzyme established hydrogen bonds.