Determination of the anti-polo like kinase 1 potential of novel derivatives of thiophene using oncoinformatics approach

Abstract

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.