Abstract：
1,3,4-Oxadiazole pharmacophore is still considered a viable biologically active scaffold for the synthesis of more effectual and broad-spectrum antimicrobial agents. Therefore, the present study is based on five 1,3,4-oxadiazole target structures, viz., CAROT, CAROP, CARON (D-A-D-A systems) and NOPON and BOPOB (D-A-D-A-D systems) bearing various bioactive heterocyclic moieties relevant to potential biological activities. Three of the compounds, CARON, NOPON and BOPOB were assessed in-vitro for their efficacy as antimicrobial agents against gram positive (Staphylococcus aureus and Bacillus cereus) and gram negative (Escherichia coli and Klebsiella pneumonia) bacteria; and two fungi, Aspergillus niger and Candida albicans; also, as an anti-tuberculosis agent against Mycobacterium tuberculosis. Most of the tested compounds displayed promising antimicrobial activity, especially CARON which was then analyzed for the minimum inhibitory concentration (MIC) studies. Similarly, NOPON portrayed the highest anti-TB activity among the studied compounds. Consequently, to justify the detected anti-TB activity of these compounds and to recognize the binding mode and important interactions between the compounds and the ligand binding site of the potential target, these compounds were docked into the active binding site of cytochrome P450 CYP121 enzyme of Mycobacterium tuberculosis, 3G5H. The docking results were in good agreement with the result of in-vitro studies. In addition, all the five compounds were tested for their cell viability and have been investigated for cell labeling applications. To conclude, one of the target compounds, CAROT was used for the selective recognition of cyanide ion by \'turn-off\' fluorescent sensing technique. The entire sensing activity was examined by spectrofluorometric method and MALDI spectral studies. The limit of detection obtained was 0.14 µM.
摘要：
1,3,4-恶二唑药效团仍然被认为是合成更有效和广谱抗微生物剂的可行生物活性支架。因此,本研究基于五个1,3,4-恶二唑靶结构，viz.,卡罗,CAROP,CARON(D-A-D-A系统)和NOPON和BOPOB(D-A-D-A-D系统)带有与潜在生物活性相关的各种生物活性杂环部分。其中三种化合物，卡隆,在体外评估了NOPON和BOPOB作为抗革兰氏阳性（金黄色葡萄球菌和蜡状芽孢杆菌）和革兰氏阴性（大肠杆菌和肺炎克雷伯菌）细菌的抗菌药物的功效；和两种真菌，黑曲霉和白色念珠菌；还有，作为抗结核分枝杆菌的抗结核剂。大多数测试的化合物显示出有希望的抗菌活性，特别是CARON，然后对其进行最低抑制浓度（MIC）研究。同样，NOPON描绘了所研究化合物中最高的抗TB活性。因此,证明检测到的这些化合物的抗TB活性，并识别化合物与潜在靶标的配体结合位点之间的结合模式和重要相互作用，这些化合物停靠在结核分枝杆菌细胞色素P450CYP121酶的活性结合位点，3G5H。对接结果与体外研究结果吻合良好。此外,测试了所有5种化合物的细胞活力，并进行了细胞标记应用研究。最后，目标化合物之一，CAROT用于通过“关闭”荧光传感技术选择性识别氰化物离子。通过荧光光谱法和MALDI光谱研究检查了整个传感活动。获得的检测限为0.14µM。
