In quest of promising anticancer agents, the pharmacophores of natural (β-carboline) and synthetic origin (benzothiazole) were adjoined by a carboxamide bridge and three-point diversification was accomplished. The in vitro cytotoxic ability of the compounds was established on adherent and suspension human cancer cell lines and compounds 8u and 8f advanced as pre-eminent molecules with IC₅₀ values of 1.46 and 1.81 μM respectively in A549 cell line. The cytospecificity was entrenched for potent compounds 8u and 8f by evaluating against normal human lung epithelial cells and selectivity index was calculated. Furthermore, EtBr displacement, relative viscosity and gel-based topoisomerase II target assays unveiled the intercalative topo-II inhibitory capability and DNA binding studies (absorbance) revealed the dissociation constant (K_d) for compounds 8u and 8f as 98 and 103 μM respectively. Additionally, cell-based flow cytometric assays like Annexin-V/PI dual staining aids in the quantification of apoptosis induced and JC-1 staining disclosed the depolarization of mitochondrial membrane potential by compound 8u in A549 cells in a dose-dependent manner. Moreover, wound healing assay established the inhibition of in vitro cell migration by compound 8u on A549 cells. In addition, molecular docking studies proved the binding of compounds 8u and 8f in the active site of DNA complexed with topo IIα and stabilized by interactions with DNA base pairs and amino acid residues. Remarkably, the compounds 8u and 8f follow Lipinski’s rule of five and are in the recommended range for Jorgensen’s rule of three with a minimal violation and other pharmacokinetic parameters revealing druggability of the synthesized hybrids.

为了寻找有希望的抗癌剂，天然（β-咔啉）和合成来源（苯并噻唑）的药效团通过羧酰胺桥连接，并实现了三点多样化。在体外的化合物的细胞毒性能力成立于贴壁和悬浮的人癌细胞系和化合物8U和8F Advanced作为杰出分子与集成电路_50倍中的A549细胞系分别为1.46的值和1.81μM。有效化合物8u和8f具有细胞特异性通过对正常人肺上皮细胞的评价和选择性指数计算。此外，EtBr 置换、相对粘度和基于凝胶的拓扑异构酶 II 靶标测定揭示了插入式拓扑 II 抑制能力和 DNA 结合研究（吸光度）显示化合物8u和8f的解离常数（K _d）分别为 98 和 103 μM。此外，基于细胞的流式细胞分析，如 Annexin-V/PI 双染色有助于量化诱导的细胞凋亡和 JC-1 染色，揭示了化合物8u在 A549 细胞中以剂量依赖性方式对线粒体膜电位的去极化。此外，伤口愈合试验建立了体外抑制化合物8u在 A549 细胞上的细胞迁移。此外，分子对接研究证明了化合物8u和8f在与拓扑 IIα 复合的 DNA 活性位点上的结合，并通过与 DNA 碱基对和氨基酸残基的相互作用而稳定。值得注意的是，化合物8u和8f遵循 Lipinski 的五法则，并且在 Jorgensen 的三法则的推荐范围内，具有最小的违反和揭示合成杂化物的成药性的其他药代动力学参数。