Synthesis and In Silico Targeting of PIM‐1 Kinase by Isatin–Triazole‐Appended Pyrano[2,3‐c]Pyrazolone Scaffolds for Prostate Cancer Therapy

Abstract

Prostate cancer continues to be a significant contributor to cancer‐related morbidity and mortality in the male population globally. In this context, the current study presents the design, synthesis, and in silico assessment of a structurally integrated new series of isatin–triazole‐appended pyrano[2,3‐c]pyrazolone hybrids aimed at evaluating their potential as PIM‐1 kinase‐targeting anticancer agents. Their molecular recognition potential was subsequently examined in relation to human PIM‐1 kinase. Molecular docking analysis showed significant binding interactions within the PIM‐1 active site, with compound 11a demonstrating the most favorable binding affinity (−10.4 kcal/mol) among the synthesized derivatives. It is noteworthy that the predicted affinity was more favorable as compared to the established PIM‐1 inhibitors SGI‐1776 (−9.2 kcal/mol) and AZD1208 (−8.5 kcal/mol). Furthermore, in silico ADMET profiling demonstrated promising drug‐likeness and pharmacokinetic characteristics throughout the series. Collectively, the integrated synthetic and computational results highlight the isatin–triazole–pyrano[2,3‐c]pyrazolone scaffold, specifically 11a , as a noteworthy candidate for subsequent PIM‐1‐focused research endeavors. The study provides a logical foundation for future experimental validation, encompassing biochemical PIM‐1 inhibition and assessment against prostate cancer cell models, aimed at the development of structurally innovative anticancer lead candidates.