Javaid Maryam, Haq Ihsan-Ul, Nadeem Humaira, Fatima Humaira, Khan Arif-Ullah, Irshad Nadeem
Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.
Front Pharmacol. 2023 Feb 27;14:1084181. doi: 10.3389/fphar.2023.1084181. eCollection 2023.
Multidrug resistance and infectious disease have enormous spread despite drug discovery and development advancements. 1, 2, 4 -triazoles have been extensively studied, playing an imperative role in many pathologic conditions. A series of Schiff base triazoles; derived from Indole -3- acetic acid with substituted Benzaldehydes (5a-5g) were designed, synthesized, and evaluated through various Spectroanalytical techniques. SwissADME was used to assess physicochemical properties and pharmacokinetic drug-likeliness behavior. (5a-5g) were evaluated for their varied biological potential through antioxidant, antimicrobial, enzyme inhibition, and cytotoxic evaluation. Schiff bases express drug-like nature as they follow Lipinski's rule of five. showed good antioxidant potential in total antioxidant capacity (TAC) and total reducing power (TRP) assays and was most active in the library in % free radical scavenging assay (%FRSA), showing 32% inhibition at 50 μg/mL concentration. Compounds showed antibacterial activity against various tested strains. showed a minimum inhibitory concentration (MIC) value of 3.12 μg/mL for and ., respectively. In the antifungal assay, only inhibited one strain with a zone of inhibition >6 mm. These synthetic molecules possess good cytotoxic potential in the Brine Shrimp Lethality screening; exhibited LC5.7 μg/mL. In the protein kinase inhibition assay, and demonstrated inhibitory potential, showcasing the zone of inhibition as 7.5-10.5 mm for the bald one and 6-7.5 for the clear zone. These findings suggest that the compounds have antibacterial and cytotoxic potential, and there is a chance for further research and development in this area.
尽管在药物发现和开发方面取得了进展,但多药耐药性和传染病仍在广泛传播。1,2,4-三唑已被广泛研究,在许多病理状况中发挥着至关重要的作用。设计、合成了一系列由吲哚-3-乙酸与取代苯甲醛衍生的席夫碱三唑(5a-5g),并通过各种光谱分析技术进行了评估。使用SwissADME评估其理化性质和药代动力学药物相似性。通过抗氧化、抗菌、酶抑制和细胞毒性评估对(5a-5g)的多种生物活性进行了评价。席夫碱符合Lipinski的五规则,具有类药物性质。在总抗氧化能力(TAC)和总还原能力(TRP)测定中显示出良好的抗氧化潜力,在自由基清除率测定(%FRSA)中在文库中活性最高,在50μg/mL浓度下显示出32%的抑制率。化合物对各种测试菌株显示出抗菌活性。对金黄色葡萄球菌和大肠杆菌的最低抑菌浓度(MIC)值分别为3.12μg/mL。在抗真菌试验中,只有一个菌株对一种化合物的抑菌圈>6mm。这些合成分子在卤虫致死性筛选中具有良好的细胞毒性潜力;一种化合物的LC50为7.5μg/mL。在蛋白激酶抑制试验中,两种化合物显示出抑制潜力,空白对照的抑菌圈为7.5-10.5mm,透明区为6-7.5mm。这些发现表明这些化合物具有抗菌和细胞毒性潜力,并且在该领域有进一步研究和开发的机会。