目的:-“本研究旨在合成抗菌药物,分子对接,和DFT研究苯并噻唑-咪唑啉酮支架\“背景:苯并噻唑和咪唑啉酮类似物由于其针对微生物感染的潜在活性而受到关注。寻找合适的抗菌化合物,我们在这里报告综合,表征,苯并噻唑和咪唑酮类似物(4a-l)的生物活性。
目的:合成了苯并噻唑簇状咪唑酮基序,characterized,并筛选它们的抗菌活性。根据获得的生物活性结果,进行了分子对接以开发抗菌剂。
方法:我们通过在寻找抗菌剂(4a-l)中使用多步反应合成了一系列新的苯并噻唑簇状咪唑酮杂化物。通过1HNMR确定结构,13CNMR,IR,和质谱技术。此外,通过使用系列Broth稀释法评估合成的化合物的抗菌活性。
结果:对病原菌的体外抗菌活性进行了评估,其中,化合物4c对革兰氏阴性细菌显示出更有效的生物活性,大肠杆菌,MIC值为50μg/mL,和具有100μg/mL的MIC值的对锁骨曲霉具有活性的化合物4c。对大肠杆菌DNA旋转酶B进行了分子对接研究,以了解化合物4c的结合相互作用,并且观察到化合物4c通过疏水相互作用与活性位点的Arg76氨基酸相互作用。
结论:苯并噻唑簇状咪唑酮杂种(4a-l)具有良好的抗菌活性。其中,化合物4b(MIC=50μg/mL白色念珠菌),4c(MIC=50μg/mL,大肠杆菌),4e(MIC=100μg/mL,A.尼日尔),和4g(MIC=50μg/mL,S.pyogones)与吸电子溴,氯,与标准药物相比,苯并噻唑-咪唑酮杂化物上苯环对位的氟基团显示出显着的效力。结合亲和力得分与体外抗微生物活性(4c)密切相关,而它们的结合模式提出了空间参与,静电,以及与活性位点的氢键相互作用。
OBJECTIVE: This study aims to synthesize antimicrobial agents and their molecular docking, and DFT studies of benzothiazole-
imidazolone scaffolds.
BACKGROUND: Benzothiazole and
imidazolone analogues are of interest due to their potential activity against microbial infections. In search of suitable antimicrobial compounds, we report here the synthesis, characterization, and biological activities of benzothiazole and imidazolone analogues (4a-l).
OBJECTIVE: The benzothiazole clubbed
imidazolone motifs were synthesized, characterized, and screened for their antimicrobial activity. Molecular docking was carried out for the development of antimicrobial agents based on the results of biological activity obtained.
METHODS: We have synthesized a new series of benzothiazole-clubbed
imidazolone hybrids by using multi-step reactions in the search for antimicrobial agents (4a-l). The structures were determined by 1H NMR, 13C NMR, IR, and mass spectroscopy techniques. Moreover, synthesized compounds were evaluated for their antimicrobial activity by using a Serial Broth Dilution method. In addition, molecular electrostatic potential, geometric optimization, and molecular reactivity analyses (HOMO-LUMO) of 4c, which is one of the compounds with the highest antibacterial activity, were performed.
RESULTS: The in vitro antimicrobial activity was evaluated against pathogenic strains. Among them, compounds 4c showed the most potent biological activity against Gram-negative bacteria, E. coli with MIC values of 50 μg/mL, and compound 4c active against A. clavatus with MIC values of 100 μg/mL. Active compound 4c HUMO-LUMO energies, molecular electrostatic potential analysis, and geometric optimization parameters were calculated with a 6-31G ** base set using DFT/B3LYP theory, and the results were displayed. Molecular docking studies were performed on E. coli DNA Gyrase B to understand the binding interaction of compound 4c, and it was observed that compound 4c interacted with Arg76 amino acid of the active site through hydrophobic interaction.
CONCLUSIONS: Benzothiazole-clubbed
imidazolone hybrids (4a-l) indicated promising antimicrobial activity. Among them, compounds 4b (MIC=50 μg/mL C. albicans), 4c (MIC=50 μg/mL, E. coli), 4e (MIC= 100 μg/mL, A. niger), and 4g (MIC= 50 μg/mL, S. pyogenes) with electronwithdrawing bromo, chloro, and fluoro group at the para position of the phenyl ring on benzothiazole-imidazolone hybrids indicated remarkable potency compared to the standard drug. The geometric optimization, molecular reactivity, and MESP analyses of 4c were calculated with the B3LYP/6-31G ** base set and ΔE = ELUMO-EHOMO, which was found to be - 0.12096 eV. In addition, the binding affinity scores correlated well with the in vitro antimicrobial activity (4c), while their binding modes proposed the involvement of steric, electrostatic, and hydrogen- bonding interactions with the active site.