Salehzadeh Fatemeh, Esmkhani Maryam, Noori Milad, Javanshir Shahrzad, Iraji Aida, Mahdavi Mohammad
Pharmaceutical and Heterocyclic Compounds Research Laboratory, Department of Chemistry, Iran University of Science and Technology, Tehran, Iran.
Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Front Chem. 2024 Nov 25;12:1472342. doi: 10.3389/fchem.2024.1472342. eCollection 2024.
The increasing prevalence of antibiotic-resistant pathogens necessitates the urgent development of new antibacterial agents. Concurrently, synthetic chemistry is moving towards more sustainable practices that minimize environmental impact. This study aims to synthesize 3-aryl-2-benzo[b][1,4]oxazin-2-one derivatives, including the natural product cephalandole A, using a sustainable approach that avoids metal catalysts.
We employed nucleophilic aromatic substitution (SNAr) under microwave-assisted conditions to facilitate the synthesis of the targeted compounds. This metal-free carbon-carbon coupling reaction was optimized for efficiency, yielding good results with reduced reaction times. The synthesized derivatives were then subjected to an molecular docking study to predict their antibacterial potential against key bacterial targets, focusing on the binding affinity and interaction profiles.
The microwave-assisted SNAr method provided good yields of 55% to 82% and significantly reduced reaction times ranging from 7 to 12 minutes, simplifying the overall workup process. Among the synthesized compounds, 3-(-indol-3-yl)-6-methyl-2H-benzo[b][1,4]oxazin-2-one () emerged as a promising candidate, demonstrating favorable binding interactions in the molecular docking studies.
The integration of sustainable synthetic methodologies with in silico screening offers a novel and effective strategy for drug discovery. Our findings highlight the potential of the synthesized compounds as antibacterial agents and emphasize the importance of adopting eco-friendly approaches in pharmaceutical chemistry. This research contributes to the global effort to combat antibiotic resistance by providing new compounds for further biological evaluation.
抗生素耐药病原体的日益流行使得迫切需要开发新的抗菌剂。与此同时，合成化学正朝着更可持续的方向发展，以尽量减少对环境的影响。本研究旨在采用一种避免使用金属催化剂的可持续方法，合成3-芳基-2-苯并[b][1,4]恶嗪-2-酮衍生物，包括天然产物头菌素A。
我们在微波辅助条件下采用亲核芳香取代反应（SNAr）来促进目标化合物的合成。这种无金属的碳-碳偶联反应针对效率进行了优化，在缩短反应时间的情况下取得了良好的结果。然后对合成的衍生物进行分子对接研究，以预测它们对关键细菌靶点的抗菌潜力，重点关注结合亲和力和相互作用特征。
微波辅助的SNAr方法提供了55%至82%的良好产率，并显著缩短了反应时间，从7分钟到12分钟不等，简化了整个后处理过程。在合成的化合物中，3-（-吲哚-3-基）-6-甲基-2H-苯并[b][1,4]恶嗪-2-酮（）成为一个有前景的候选物，在分子对接研究中表现出良好的结合相互作用。
将可持续合成方法与计算机筛选相结合，为药物发现提供了一种新颖而有效的策略。我们的研究结果突出了合成化合物作为抗菌剂的潜力，并强调了在药物化学中采用环保方法的重要性。这项研究通过提供新的化合物进行进一步的生物学评估，为全球对抗抗生素耐药性的努力做出了贡献。
