Bavachin, Bavachinin, Maesopsin, Garcinoic Acid, and Bilobol as Anaplastic Lymphoma Kinase Inhibitors: In Vitro and in Silico Studies

Abstract

Several new natural compounds were investigated as ALK inhibitor compounds. Bavachin, bavachinin, maesopsin, garcinoic acid, and bilobol Compounds, which have active groups, and also can inhibit ALK enzymatic tests (IC50: 0.018 ± 0.007, 1.830 ± 0.012, 9.141 ± 0.301, 0.048 ± 0.003, and 0.970 ± 0.030 μM, respectively). Bavachin, Garcinoic acid, and Bilobol were identified as the best inhibitors, and then the antiproliferative activity of these compounds was studied. Additionally, the studies continued with bilobol, Bilobol against various receptor tyrosine Kinases, various ALK Mutants, CYP450 Enzymes, and hERG studies were performed, and comparisons were made with standards. The investigation of the biological activities of certain natural compounds against a variety of enzymes was conducted using molecular modeling and molecular simulation. Computational techniques were utilized to assess the effectiveness of the natural compounds in inhibiting ALK and specific mutations of this kinase. Additionally, the binding affinity of these compounds to various receptor tyrosine kinases, including EGFR, c-Met, VEGFR2, c-Src, IGF1R, and JAK2, was analyzed. The results emphasized the interactions between atoms, demonstrating that the compounds formed strong connections with the proteins. These natural compounds exhibit the potential to suppress enzyme activity and hinder the proliferation of cancer cells. Natural products have long been the sole source of viable lead compounds for medicinal chemists. They have also given clinical practice access to a large number of potential medication candidates for the therapy of a variety of conditions.