Discovery of newer 1,3,4-Oxadiazole clubbed Isoindoline-1,3-dione derivatives as potential anticancer agents: Design, machine learning, synthesis, molecular docking, ADMET, DFT and MD simulation.

Cancer remains to be the second leading cause of death, since the available drugs and therapies may get failure due to the early-stage drug resistance, metastasis, poor pharmacokinetics, and toxic effects. This gap can be fulfilled by designing potential anticancer agent with the Phthalimide as a prime scaffold. The robust and reliable pharmacophore model was used for the designing of newer Phthalimide derivatives. Additionally, we clubbed 1,3,4-Oxadiazole with Phthalimide to fulfil these features. The predicted IC for all the designed compounds are in µM range and DFT study also confirmed the reactive nature of these molecules. The designed compounds were synthesized and characterized by FT-IR, H NMR, C NMR and Mass spectroscopy. The in-vitro anticancer evaluation was carried out by performing MTT assay on MCF-7 and HCT-116 cancer cell lines. All compounds showed moderate to potent anticancer activity. The compound B19 was found to be the most potent against both the MCF-7 and HCT-116 with IC of 3.468 and 4.508 µM respectively. All the compounds showed good docking score in terms of binding affinity, lib dock score, CDOCKER interaction and binding free energy. MD Simulation study reviled good stability, compactness and rigidity of potent compound throughout the 100 ns run. ADMET results supports the good pharmacokinetics and lower toxicity. In conclusion, we suggest the compound B19 is potential drug-like candidate can be utilized in anticancer treatment on further confirmations. This study is widely useful for the medicinal chemists and scientific community.