In vitro cytotoxicity evaluation of thiourea derivatives bearing Salix sp. constituent against HK-1 cell lines

Abstract

In searching for drugs from natural product scaffolds has gained interest among researchers. In this study, a series of twelve halogenated thiourea (ATX 1-12) via chemical modification of aspirin (a natural product derivative) and evaluated for cytotoxic activity against nasopharyngeal carcinoma (NPC) cell lines, HK-1 via MTS-based colorimetric assay. The cytotoxicity studies demonstrated that halogens at meta position of ATX showed promising activity against HK-1 cells (IC₅₀ value ≤15 µM) in comparison to cisplatin, a positive cytotoxic drug (IC₅₀ value =8.9 ± 1.9 µM). ATX 11, bearing iodine at meta position, showed robust cytotoxicity against HK-1 cells with an IC₅₀ value of 4.7 ± 0.7 µM. Molecular docking interactions between ATX 11 and cyclooxygenase-2 demonstrated a robust binding affinity value of −8.1 kcal/mol as compared to aspirin’s binding affinity value of −6.4 kcal/mol. The findings represent a promising lead molecule from natural product with excellent cytotoxic activity against NPC cell lines.

Graphical Abstract

Keywords:

• Aspirin
• thiourea
• cytotoxicity
• molecular docking
• cyclooxygenase-2

Acknowledgements

We acknowledge support from Universiti Malaysia Sarawak and Malaysia Ministry of Science, Technology and Innovation for the financial support through FRGS/ST02(01)/1115/2014(01) and FRGS/ST01(01)/1298/2015(15). We also acknowledge Universiti Sultan Zainal Abidin for grant support through UniSZA/2017/DPU/02. We thank Universiti Teknologi MARA for providing CHN elemental analysis services and Corine Neilsen for outstanding editing and proof reading of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

We acknowledge support from Universiti Malaysia Sarawak and Malaysia Ministry of Science, Technology and Innovation for the financial support through FRGS/ST02(01)/1115/2014(01) and FRGS/ST01(01)/1298/2015(15). We also acknowledge Universiti Sultan Zainal Abidin for grant support through UniSZA/2017/DPU/02. We thank Universiti Teknologi MARA for providing CHN elemental analysis services and Corine Neilsen for outstanding editing and proof reading of the manuscript.