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Purpose: To explore the anticancer mechanistic aspect of thiophene derivatives via targeting Polo like kinase 1 (PLK1). Methods: The PLK1 enzyme is primarily expressed in cancer cells, and blocking its active site is one of the plausible ways to target cancer. Thus, in the present study, the thiophene derivatives were tested against PLK1 by molecular docking approach. Results: Thiophene derivatives, named 8A, 8B and 14, exhibited better interactions with PLK1 active site than the positive control, doxorubicin. Molecular docking experiments revealed that 8A, 8B and 14 interacted efficiently with PLK1, and demonstrated binding energy and inhibition constant scores of ꞌ- 8.02 kcal/mol and 1.33 μMꞌ, ꞌ-8.65 kcal/mol and 0.454 μMꞌ and ꞌ-8.33 kcal/mol and 0.788 μMꞌ, respectively. In contrast, doxorubicin-PLK1 interaction had binding energy of -7.95 kcal/mol and inhibition constant of 2.75 μM. Conclusion: These results predict that thiophene derivatives 8A, 8B and 14 might exert anticancer effect by inhibiting PLK1 activity. Although, wet lab experiments are required to validate the data, however, these results may pave the way for the development of novel PLK1 inhibitors for anticancer therapy.

Myostatin is a widely recognized inhibitory factor of skeletal muscle growth and significantly influences muscle development and metabolism. In mice, myostatin inhibition improves insulin sensitivity, increases glucose uptake by skeletal muscle, and reduces body fat. Furthermore, Mss51 is downregulated in response to myostatin inhibition, and its deletion appears to improve the metabolic state of skeletal muscle and reduce adipose tissue, which makes Mss51 a potential target for the treatment of obesity and type 2 diabetes. Here, we report a computationally predicted and validated three-dimensional structure of Mss51. Computational screening was used to identify naturally occurring compounds from the Herbal and Specs chemical database that might inhibit Mss51, based on binding affinities and physiochemical and ADMET properties. ZINC00338371, ZINC95099599 and ZINC08214878 were found to bind to Mss51 with high binding affinity and specificity. In addition, 100 ns molecular dynamics simulations were conducted to assess the stabilities of the interactions between the three compounds and Mss51. MD simulation demonstrated that all three compounds bind to the active pocket site of Mss51 stably and cause conformation changes. ZINC00338371 was found to bind most stably with binding free energy −229.022 ± 13.776 kJ/mol to Mss51, suggesting that it has therapeutic potential as a treatment option for obesity and type 2 diabetes. Communicated by Ramaswamy H. Sarma