Yogananda Bhargav, Roy Srijita, Pravallika M Sathya Naga Bala, Rajan Reshma, George Kevin, Sarangi Ashish K, Rajagopalan Sanjay, Desikan Rajagopal
Department of Chemistry, School of Advanced Sciences, Vellore Institute of Technology-Vellore, Vellore, Tamilnadu, India.
Department of chemistry, Centurion University of Technology and Management, Balangir, Odisha, India.
Cell Biochem Biophys. 2025 Jun 28. doi: 10.1007/s12013-025-01807-1.
Chronic inflammation plays a pivotal role in the development and progression of cardiovascular diseases (CVDs), posing a significant threat to global health. This study presents the synthesis and comprehensive characterization of N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-6-nitrobenzo[d][1,3]dioxole-5-carboxamide (EMC), a promising therapeutic candidate for inflammation-related CVD treatment. Insights into EMC's physicochemical properties were gained through density functional theory (DFT) studies, revealing an energy gap, ΔE (E-E) = 2.97 eV. Hirshfeld surface analysis and molecular electrostatic potential (MEP) elucidated its crystal packing and charge distribution. Pharmacokinetic predictions (Swiss ADME and pkCSM) indicated EMC's drug-like behaviour, supporting its therapeutic potential. Molecular docking demonstrated selective COX-2 inhibition by EMC, with a docking score of -8.02 kcal/mol and key interactions involving ARG A:376, VAL A:538, ASN A:537, and GLN A:374. The results underscore the potential of EMC as a selective COX-2 inhibitor, offering anti-inflammatory benefits in CVD management. Furthermore, EMC exhibited promising antioxidant characteristics with IC values of 21.56 ± 3.99 μM (ABTS) and 41.9 ± 5.17 μM (DPPH). This preliminary investigation contributes significantly to the development of novel therapeutic agent EMC for inflammation related CVDs, transiting for future in vitro and in vivo COX-2 inhibition studies.
慢性炎症在心血管疾病（CVDs）的发生和发展中起关键作用，对全球健康构成重大威胁。本研究介绍了N-(2,3-二氢苯并[b][1,4]二恶英-6-基)-6-硝基苯并[d][1,3]二恶唑-5-甲酰胺（EMC） 的合成及全面表征，EMC是一种有前景的用于治疗炎症相关心血管疾病的候选药物。通过密度泛函理论（DFT）研究获得了EMC的物理化学性质的见解，揭示了能隙ΔE (E-E) = 2.97 eV。 Hirshfeld表面分析和分子静电势（MEP）阐明了其晶体堆积和电荷分布。药代动力学预测（Swiss ADME和pkCSM）表明EMC具有类药物行为，支持其治疗潜力。分子对接表明EMC对COX-2有选择性抑制作用，对接分数为-8.02 kcal/mol，关键相互作用涉及ARG A:3７6、VAL A:538、ASN A:537和GLN A:374。结果强调了EMC作为选择性COX-2抑制剂的潜力，在心血管疾病管理中具有抗炎益处。此外，EMC表现出有前景的抗氧化特性，ABTS的IC值为21.56±3.99 μM，DPPH的IC值为41.9±5.17 μM。这项初步研究对开发用于治疗炎症相关心血管疾病的新型治疗剂EMC有重大贡献，为未来的体外和体内COX-2抑制研究过渡。
