Ahsan Mohamed Jawed, Kumar Vivek, Ali Amena, Ali Abuzer, Yusuf Mohammad, Ahmad Iqrar, Patel Harun, Ahsan Md Faiyaz
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jahangirabad Institute of Technology, Barabanki, Uttar Pradesh, India.
Department of Pharmaceutical Chemistry, Maharishi Arvind College of Pharmacy, Ambabari Circle, Jaipur, Rajasthan, India.
Future Med Chem. 2025 May;17(10):1143-1154. doi: 10.1080/17568919.2025.2504335. Epub 2025 May 15.
Cancer is the second leading cause of death and chemotherapy is widely used and well-known for treating cancer, yet it has lots of adverse side effects, making the search for novel compounds imperative. We reported here design, synthesis, DFT analysis, anticancer evaluation and in-silico studies of new 1,3,4-oxadiazoles (4a-e).
IMC-038525 and IMC-094332 tubulin inhibitors' oxadiazole-linked aryl cores inspired the innovative compounds, and synthesis was accomplished in two steps followed by their characterization by spectral data. The HOMO and LUMO energy gap (ΔE) was determined to investigate compounds' (4a-e) stability followed by their anticancer activity at 10 μM and in-silico studies.
5-(4-Nitrophenyl)-N-(naphthalene-2-yl)-1,3,4-oxadiazol-2-amine (4b) demonstrated substantial anticancer activity against a few cell lines like SR, MDA-MB-435, MOLT-4, K-562, and HL-60(TB). 5-(3,4,5-Trimethoxyphenyl)-N-(naphthalene-2-yl)-1,3,4-oxadiazol-2-amine (4e) demonstrated promising anticancer activity against cell lines, UO-31, NCI-H226, CAKI-1, PC-3, and MCF7. The molecular docking against tubulin's colchicine binding site (PDB ID: 1AS0), displayed a docking score of -7.295 Kcal/mol and a H-bond interaction with Ala317 residue for the ligand 4e. The ligand 4e was found to interacted 24 amino acids of the tubulin protein in MD simulation investigation with moderate local conformational changes with ligand 4e (< 1 Å).
癌症是第二大致死原因，化疗被广泛用于治疗癌症且广为人知，但其有许多不良副作用，因此寻找新型化合物势在必行。我们在此报告了新型1,3,4 - 恶二唑（4a - e）的设计、合成、密度泛函理论（DFT）分析、抗癌评估及计算机模拟研究。
IMC - 038525和IMC - 094332微管蛋白抑制剂的恶二唑连接芳基核心启发了这些创新化合物，合成分两步完成，随后通过光谱数据对其进行表征。测定了最高已占分子轨道（HOMO）和最低未占分子轨道（LUMO）的能隙（ΔE）以研究化合物（4a - e）的稳定性，随后在10 μM浓度下研究其抗癌活性并进行计算机模拟研究。
5 - （4 - 硝基苯基） - N - （萘 - 2 - 基） - 1,3,4 - 恶二唑 - 2 - 胺（4b）对SR、MDA - MB - 435、MOLT - 4、K - 562和HL - 60（TB）等几种细胞系表现出显著的抗癌活性。5 - （3,4,5 - 三甲氧基苯基） - N - （萘 - 2 - 基） - 1,3,4 - 恶二唑 - 2 - 胺（4e）对UO - 31、NCI - H226、CAKI - 1、PC - 3和MCF7细胞系表现出有前景的抗癌活性。针对微管蛋白秋水仙碱结合位点（PDB ID：1AS0）的分子对接显示，配体4e的对接分数为 - 7.295千卡/摩尔，且与Ala317残基存在氢键相互作用。在分子动力学（MD）模拟研究中发现配体4e与微管蛋白的24个氨基酸相互作用，配体4e引起的局部构象变化适中（<1 Å）。
