Triethylammonium salt of a synthesized dicoumarol: Structural insight and human anti-glioblastoma activities

Afzal Khan; Muhammad Ikram; Sadia Rehman; Rizwan Khan; Vinay K Puduvalli; Ayub Jadoon; Momin Khan; Fawaz Alasmari; Abdullah F AlAsmari

doi:10.1016/j.heliyon.2023.e17601

Triethylammonium salt of a synthesized dicoumarol: Structural insight and human anti-glioblastoma activities

Heliyon. 2023 Jun 25;9(7):e17601. doi: 10.1016/j.heliyon.2023.e17601. eCollection 2023 Jul.

Authors

Afzal Khan^{1

2

3}, Muhammad Ikram¹, Sadia Rehman¹, Rizwan Khan⁴, Vinay K Puduvalli⁴, Ayub Jadoon², Momin Khan¹, Fawaz Alasmari⁵, Abdullah F AlAsmari⁵

Affiliations

¹ Department of Chemistry, Abdul Wali Khan University, Mardan, Pakistan.
² Department of Microbiology, Abbotabad University of Science and Technology, Abbotabad, Pakistan.
³ Department of Neuro-Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁴ Department of Zoology, Abdul Wali Khan University, Mardan, Pakistan.
⁵ Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

Abstract

Glioblastoma multiforme (GBM) is the most common and primary brain tumor with poor prognosis. They are removed by following tedious and life threatening surgeries. GBM stem cells (GSCs) are the main source of tumor recurrence after surgery. Hence, drugs are designed to overcome the recurrent glioblastoma malignant cells. Currently used chemotherapies are not cost effective as well as bear resistance. New and effective chemotherapeutic compounds are developed to overcome the intrinsic and acquired resistance. Dicoumarol derivative 3,3'-[(4-methoxyphenyl)methanediyl]bis(4-hydroxy-2Hchromen-2-one) (HL) and its triethylammonium salt triethylammonium3-[(4-methoxyphenyl)(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl]-2-oxo-2H-chromen-4-olate (L) were synthesized and characterized using spectral and analytical techniques. The deprotonated compound L was further studied structurally using single crystal analysis. Cytotoxic studies against human glioblastoma cells A172 and LN229 were investigated both dose and time dependently and compared with the cytotoxicity of normal human astrocytes (NHA). The IC₅₀ value of HL against A172 was found to be lying within the range 2.68-0.95 μM whereas against LN229 the range was found to be 9.55-0.85 μM. Similarly, the compound L revealed range of 1.9-0.271 μM against A172 and 1.2-0.27 μM against LN229. Cell cycle arrest was observed in GBM cells treated with L compared to the control group, which suggested that L may trigger apoptosis in GBM cells according to cytotoxicity and flow cytometry results. The antioxidant activity of synthesized compounds was also investigated using DPPH free radicals.

Keywords: Dicoumarol; Dicoumarol triethylammonium salt; Flow cytometry; Free radical scavenging; Glioblastoma; Phase contrast microscopy.