Bhoomandla Srinu, Chennuri Bharath Kumar, Sirisha Surapaneni, Ganji Saidulu, Trivedi Rashmi, Karunasri Ananthoju, Pandiri Sreedhar
Department of Chemistry, Geethanjali College of Engineering and Technology, Cheeryal, Keesara, Medchal, Telanagana, 501301, India.
Department of Chemistry, School of Science, GITAM (Deemed to be University), Hyderabad, Telangana, 502329, India.
Chem Biodivers. 2025 Feb;22(2):e202401313. doi: 10.1002/cbdv.202401313. Epub 2024 Nov 9.
Flurbiprofen, a primary component of a nonsteroidal anti-inflammatory drug (NSAID) used to relieve symptoms of arthritis, and is a considerable interest in medicinal chemistry due to its demonstrated potential as an effective agent in various therapeutic applications. In consideration of the 1,3,4-oxadiazole therapeutic potential and anticancer activity, a new series of flurbiprofen scaffolds have been prepared through a straightforward reaction between 5-(1-(2-fluoro-[1,1'-biphenyl]-4-yl)ethyl)-1,3,4-oxadiazole-2-thiol (4) and various organic active 2-chloro-N-phenyl acetamides (5). The synthesized series (6a-6k) was characterized using a combination of spectroscopic techniques, including FT-IR, mass, H-NMR, and C NMR, followed by physical data. The cytotoxicity of the newly synthesized congeners was investigated against MCF-7 (human breast cancer cell line) and A-549 (human lung carcinoma epithelial) cell lines and anti-inflammatory activity as DPPH and HO radical scavenging ability. In the series, analogues 6c, 6e, 6h, and 6k showed excellent inhibitory activity against MCF-7 cells in the range of IC values of 9.10-13.67 μg mL compared to DXN (IC=9.24 μg mL). In this series, analogues 6c, 6f, 6h, and 6j show remarkable HO radical scavenging inhibition IC of 48.25±0.21, 47.33±0.15, 51.10±0.25, and 44.40±0.07 μM by using ascorbic acid as a standard, whose IC is 49.90±0.27 μM. According to the docking results, the most potent cytotoxic compounds have a stronger binding affinity with the Flurbiprofen complex (PDB: 1R9O) because of their interactions with residues such as Arg(A), Trp(A), Phe(A), Gly(A), Ile(A), Glu(A), Thr(A), Val(A), Phe(A), Leu(A), Ile(A), and Cys(A). Furthermore, in silico drug-likeness prediction analysis suggested that the majority of the synthesized compounds exhibit good oral bioavailability based on their Lipinski's Rule of Five and toxicity using ADME/Tox predictions.
氟比洛芬是一种用于缓解关节炎症状的非甾体抗炎药（NSAID）的主要成分，由于其在各种治疗应用中显示出作为有效药物的潜力，因此在药物化学领域备受关注。考虑到1,3,4-恶二唑的治疗潜力和抗癌活性，通过5-(1-(2-氟-[1,1'-联苯]-4-基)乙基)-1,3,4-恶二唑-2-硫醇（4）与各种有机活性2-氯-N-苯基乙酰胺（5）之间的直接反应，制备了一系列新的氟比洛芬支架。使用包括傅里叶变换红外光谱（FT-IR）、质谱、氢核磁共振（H-NMR）和碳核磁共振（C NMR）在内的多种光谱技术对合成的系列化合物（6a - 6k）进行了表征，随后测定了物理数据。研究了新合成同系物对MCF-7（人乳腺癌细胞系）和A-549（人肺癌上皮细胞系）细胞系的细胞毒性以及作为二苯基苦味酰基自由基（DPPH）和羟基自由基（HO）清除剂的抗炎活性。在该系列中，与DXN（IC = 9.24 μg·mL）相比，类似物6c、6e、6h和6k在IC值为9.10 - 13.67 μg·mL范围内对MCF-7细胞表现出优异的抑制活性。在该系列中，以抗坏血酸为标准，类似物6c、6f、6h和6j对HO自由基清除的抑制IC分别为48.25±0.21、47.33±0.15、51.10±0.25和44.40±0.07 μM，抗坏血酸的IC为49.90±0.27 μM。根据对接结果，最具细胞毒性的化合物由于与精氨酸（A）、色氨酸（A）、苯丙氨酸（A）、甘氨酸（A）、异亮氨酸（A）、谷氨酸（A）、苏氨酸（A）、缬氨酸（A）[此处原文可能多了一个Phe(A)]、亮氨酸（A）、异亮氨酸（A）和半胱氨酸（A）等残基相互作用，与氟比洛芬复合物（PDB：1R9O）具有更强的结合亲和力。此外，基于Lipinski的五规则和使用ADME/Tox预测的毒性，计算机辅助药物相似性预测分析表明，大多数合成化合物具有良好的口服生物利用度。
