背景:抗菌剂的开发至关重要,原因有几个,主要是抗击传染病和应对日益增长的抗菌素耐药性威胁。尽管存在许多现有药物,但由于以下几个原因,仍需要继续开发抗微生物药物;新出现的病原体和疾病,对现有药物的保留和对现有药物的多重耐药性的传播。
目的:本研究的目的是合成和评价新合成的苯并噻唑衍生物的抗菌潜力。
方法:通过将其与氯乙酰氯和取代的2-氨基苯并噻唑反应,合成了一系列新的2-(取代的氨基)-N-(6-取代的-1,3-苯并噻唑-2基)乙酰胺BTC(a-t),并进一步与各种取代的胺回流以获得目标化合物。通过实验筛选合成的化合物对革兰氏阳性和革兰氏阴性细菌和真菌的抗菌性能。针对选定的细菌和真菌菌株确定化合物的抑制区域和最小抑制浓度。使用V-lifeMDS3.5软件(DNA促旋酶,PDB:3G75)。
结果:发现化合物BTC-nN-(6-甲氧基-1,3-苯并噻唑-2-基)-2-(吡啶-3-基氨基)乙酰胺和BTC-nN-(6-硝基-1,3-苯并噻唑-2-基)-2-(吡啶-3-基氨基)乙酰胺具有良好的抗微生物潜力。化合物BTC-j对金黄色葡萄球菌表现出良好的抗菌活性,MIC值为12.5μg/mL,枯草芽孢杆菌MIC为6.25μg/mL,大肠杆菌,MIC为3.125μg/mL,和铜绿假单胞菌的MIC为6.25μg/mL。因此,从结果来看,观察到化合物BTC-j,BTC-f,BTC-n,和BTC-r在不同浓度下表现出显著的抗菌和抗真菌潜力。
结论:本研究导致以良好收率成功合成2-乙酰氨基取代的苯并噻唑衍生物BTC(a-t)。发现化合物的对接得分和抗微生物活性是一致的。标准化合物和试验化合物的抗菌活性无统计学差异,表明测试化合物具有相当的活性。因此,苯并噻唑通过乙酰胺键连接到杂环上,可能是有前途的先导分子,可在发现有效抗菌剂的过程中进一步优化。因此,我们得出结论,合成的化合物具有作为新型抗菌剂进一步开发的潜力。
BACKGROUND: The development of antimicrobial agents is crucial for several reasons, primarily to combat infectious diseases and to address the growing threat of antimicrobial resistance. The need for the contin-ued development of antimicrobial drugs persists despite the presence of many existing drugs for several reasons viz; emerging new pathogens and diseases, reistance to existing drug and propogation of multi-drug resistance to existing drugs.
OBJECTIVE: The objective of the study was to synthesize and evaluate the antimicrobial potential of newly synthesized benzothiazole derivatives.
METHODS: A new series of 2-(substituted amino)-N-(6-substituted-1,3-benzothiazol-2yl)acetamide BTC(a-t) has been synthesized by reacting it with chloracetyl chloride with substituted 2-amino benzothiazole and further refluxed with various substituted amines to obtain target compounds. The synthesized compounds were screened experimentally for their antimicrobial property against gram-positive and gram-negative bacteria and fungi. The zone of inhibition and minimum inhibitory concentration of compounds were determined against selected bacterial and fungal strains. Further docking study was carried out to check the probable interactions with the selected protein using V-life MDS 3.5 software (DNA gyrase, PDB: 3G75).
RESULTS: Compounds BTC-j N-(6-methoxy-1,3-benzothiazol-2-yl)-2-(pyridine-3-ylamino)acetamide and BTC-r N-(6-nitro-1,3-benzothiazol-2-yl)-2-(pyridine-3-ylamino)acetamide were found to have good antimicrobial potential. The compound BTC-j showed good antibacterial activity against S. aureus at an MIC value of 12.5 μg/mL, B. subtilis at MIC of 6.25μg/mL, E. coli at MIC of 3.125μg/mL, and P. aeruginosa at MIC of 6.25μg/mL. Thus, from the result, it was observed that compounds BTC-j, BTC-f, BTC-n, and BTC-r exhibited significant antibacterial and antifungal potential at different concentrations.
CONCLUSIONS: The present study resulted in the successful synthesis of 2-acetamido substituted benzothiazole derivatives BTC(a-t) with good yields. The dock score of the compounds and the antimicrobial activity were found to be consistent. No statistical difference in the antimicrobial activity of the standard and test compounds was found, indicating that the test compounds have comparable activity. Therefore, benzothiazole linked to heterocyclic rings with an acetamide linkage may serve as promising lead molecules for further optimization in the journey to discover potent antibacterial agents. Thus, we conclude that the synthesized compounds have the potential for further development as novel antimicrobial agents.