Deciphering the anti-cancer and anti-inflammatory activity in natural bioactive compounds of Typhonium flagelliforme: in silico approaches with special target to NEK7.

Cancer is a great challenge and act as a crucial cause of death globally. Typhonium flagelliforme (T. flagelliforme), a medicinal plant, has been used to treat diverse diseases, including cancer. Consequently, natural compounds from this plant are being investigated for the development of potent and selective anti-cancer agents. A promising target, NEK7 interacts with NLRP3 to assemble the NLRP3 inflammasome critical complex in innate immune responses, and pyroptotic cell death. Altered NEK7 expression is connected to the progression of several cancers, making it a key target for therapy. However, the lack of effective NEK7 inhibitors highlights the urgent need to develop novel therapeutic strategies. The work aimed to identify potential anti-cancer compounds from T. flagelliforme that can act as NEK7 inhibitors for the management of lung cancer. We employed a range of computational techniques such as molecular docking, molecular dynamics (MD) simulations, and binding free energy (MM/PBSA) calculations, to evaluate the plant's bioactive compounds. Molecular docking revealed that several compounds, specifically Beta-Sitosterol, Cycloartane-3.beta.,25-diol, and Ergost-7-en-3-ol, showed higher binding scores -9.5 kcal/mol, -9.2 kcal/mol, and -9.4 kcal/mol, respectively, than the known reference inhibitor, F9N, which has binding scores of -9.1 kcal/mol. Further analysis through molecular dynamics simulations confirmed that Beta-Sitosterol, Cycloartane-3.beta.,25-diol, and Ergost-7-en-3-ol exhibit a strong and stable binding potential with NEK7. Moreover, binding free energy calculations showed that Cycloartane-3.beta.,25-diol has the highest binding free energy of -203.460 kJ/mol than the positive control (F9N), which has the binding free energy of -170.420 kJ/mol, strongly suggesting its effectiveness in modulating NEK7 signaling. Overall, this research shows that the compounds Cycloartane-3.beta., 25-diol and Beta-Sitosterol have great potential to inhibit NEK7, surpassing the known F9N compound. The study emphasizes the therapeutic potential of active compounds from T. flagelliforme for developing new cancer treatments.