Synthesis, molecular docking and anticancer activity of 5,5'-(phenylmethylene)bis(6-amino-2-thiouracil) derivatives

Abstract

A series of 5,5′-(phenylmethylene)bis(6-amino-2-thiouracil) derivatives (1–13) were synthesized by the condensation of 6-amino-2-thiouracil and benzaldehyde derivatives under reflux in glacial acetic acid. Nine compounds (3, 5 and 7–13) were novel. Good binding affinity (BE) in the active site of Eg5 was shown by all compounds, which ranged between −5.0 kcal mol⁻¹ to −26.7 kcal mol⁻¹. Most compounds in the series exhibited a stronger interaction than 5-fluorouracil (BE = −8.0 kcal mol⁻¹) with Eg5. The docking results were supported by cytotoxicity studies of the synthesized compounds against HeLa (cervical cancer) cell lines, where all compounds exhibited better anti-cancer activity than 5-fluorouracil (IC₅₀ = 12.08 µg mL⁻¹) at the lowest concentration (10 µg mL⁻¹) with IC₅₀ values ranging from 4.18 to 10.20 µg mL⁻¹.

Graphical Abstract

Keywords:

• 5,5′-(Phenylmethylene)bis(6-amino-2-thiouracil)
• anticancer activity
• docking studies

Disclosure statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Additional information

Funding

This research was funded by the National Research Foundation South Africa in the form of a Competitive Grant for Rated Researchers (Grant No. 118534) and Incentive Funding for Rated Researchers (Grant No. 114817). We acknowledge the Centre for High Performance Computing, Cape Town (South Africa) for docking software and cluster facilities, an initiative supported by the Department of Science and Technology of South Africa.