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Over the years, phytochemical compounds have shown compelling evidences in exhibiting powerful antitumor properties. Moreover, due to the lack of safety and high cost of cancer therapies, opportunities are being sought out in these compounds as an alternative treatment modality. Therefore, in the present study, 1,574 compounds from NPACT library were examined to excavate potent and nontoxic anaplastic lymphoma kinase (ALK) inhibitors. Notably, two pharmacophore hypotheses (AAAHP and DDRRR) were generated using ligand-based and energy-based techniques, respectively, to eliminate false-positive prediction in database screening. Furthermore, molecular docking and Prime MM/GBSA analysis were performed on the screened compounds to examine inhibitory activity against ALK. The analysis revealed that the two hits, namely, NPACT00018 and NPACT01077, exhibited better docking scores, binding energies, and also ensured excellent drug-likeness properties than the reference compound, crizotinib. Finally, the results were subjected to molecular dynamics studies to gain insight into the stability of these compounds in the binding pocket of ALK protein. Indeed, the useful predictions generated by the present computational models are of immense importance and could further speed up the anticancer drug development in the near future.

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Tankyrases belong to the poly (ADP-ribose) polymerase family epitomized as a novel group of medicinal targets with various prospective diseased conditions and it is appraised to be a challenging drug target for the intervention of multiple cancers. Thus, the principal objective of our study is to explore the dual-site selective tankyrase 1 inhibitor by employing the pharmacophore strategy. Initially, the ligand-based pharmacophore study generated five featured pharmacophore hypothesis, which was then employed for the database screening. The screened molecules were scrutinized through docking, MM/GBSA calculations and molecular simulation alongside pharmacokinetics properties. The analysis yielded potent dual-site tankyrase 1 inhibitors such as nebivolol and ondansetron from the DrugBank repository. Notably, the recognized lead molecules were perceived to have higher XP GScore and binding energy scores. Subsequently, simulation studies were executed to validate the structural stability of the lead molecules. It is worth mentioning that the existence of benzopyran and carbazole scaffolds in the lead molecules displayed anti-neoplastic activity and also facilitate the effective binding with tankyrase 1 protein. Ultimately, the IC50 values of the lead molecules were examined against the NCI-H596 cell line using a deep learning model. Indeed, these results are of immense importance and provide a clue to the experimental biologist in developing a potent tankyrase 1 dual-site inhibitor.

The innovative information about the molecular study has generated a prototype change in the insight of lung cancer, enlightening the more accurate mark for anticancerous drug design. Lung cancer is an imperative origin of tumor death all over the world and it accounts for ~ 1 in 5 of total tumor-related mortalities. Nonsmall cell lung cancer (NSCLC) is one of the deadliest diseases among cancer types. We mainly focused on the role of natural compounds in targeting NSCLC promising favorable results in tumor dissemination. Numerous studies have shown that drug resistance and relapse in tumor lead to the failure of conventional therapy. The utmost crucial reasons for demise in a tumor comprise the therapy letdown and also a disseminating of tumor cells to reserved positions in which the CSC inside the cancer is recognized as a crucial driver. A cancer stem cell is an erratic distinct inhabitant of tumor cells unveiling significant carcinogenic characteristics composed of self-regeneration and discrepancy ability. Moreover, new beneficial methods targeting these cancer stem cells are deliberated to enhance long-term proven outcomes. Herein, we outlined the cancer stem cells in lung cancer, existing CSC markers and favorable molecules targeting the SC signals in lung growth that might profit the growth of innovative NSCLC therapy.