Synthesis and anticancer activity of thiourea derivatives bearing a benzodioxole moiety with EGFR inhibitory activity, apoptosis assay and molecular docking study

Samir Y Abbas; Reem A K Al-Harbi; Marwa A M Sh El-Sharief

doi:10.1016/j.ejmech.2020.112363

Synthesis and anticancer activity of thiourea derivatives bearing a benzodioxole moiety with EGFR inhibitory activity, apoptosis assay and molecular docking study

Eur J Med Chem. 2020 Jul 15:198:112363. doi: 10.1016/j.ejmech.2020.112363. Epub 2020 Apr 23.

Authors

Samir Y Abbas¹, Reem A K Al-Harbi², Marwa A M Sh El-Sharief³

Affiliations

¹ Organometallic and Organometalloid Chemistry Department, National Research Centre, Cairo, Egypt. Electronic address: sy.abbas@nrc.sci.eg.
² Department of Chemistry, Faculty of Science, Taibah University, Almadinah Almunawarrah, Saudi Arabia.
³ Applied Organic Chemistry Department, National Research Centre, Cairo, Egypt; Faculty of Science and Arts, Mohail Asser, King Khalid University, Saudi Arabia.

PMID: 32361329
DOI: 10.1016/j.ejmech.2020.112363

Abstract

New thiourea derivatives bearing a benzodioxole moiety were synthesized via the reaction of 5-isothiocyanatobenzodioxole with amino compounds such as aromatic amines, sulfa drugs, heterocyclic amines, hydrazines and hydrazides. The anticancer activity of the synthesized thiourea derivatives was examined against HCT116, HepG2 and MCF-7 cancer cell lines. Most of thiourea derivatives revealed significant cytotoxic effect, in some cases greater than the doxorubicin. As example, IC₅₀ values of N¹,N³-disubstituted-thiosemicarbazone 7 were 1.11, 1.74 and 7.0 μM for HCT116, HepG2 and MCF7, respectively; IC₅₀ values of doxorubicin were 8.29, 7.46 and 4.56 μM, respectively. The anticancer mechanisms were studied via EGFR inhibition and apoptosis assessments, as well as molecular docking.

Keywords: Anticancer activity; Benzo[d][1,3]; Benzodioxole; Cytotoxic; Dioxol-5-yl; Thiourea.

MeSH terms

Amines / chemistry
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / pharmacology
Apoptosis
Benzodioxoles / chemistry*
Cell Line, Tumor
Drug Screening Assays, Antitumor
ErbB Receptors / antagonists & inhibitors*
Humans
Hydrazines / chemistry
Molecular Docking Simulation
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / pharmacology
Proto-Oncogene Proteins c-bcl-2 / metabolism
Structure-Activity Relationship
Thiosemicarbazones / chemistry
Thiourea / chemical synthesis*
Thiourea / pharmacology
bcl-2-Associated X Protein / metabolism

Substances

Amines
Antineoplastic Agents
BAX protein, human
BCL2 protein, human
Benzodioxoles
Hydrazines
Protein Kinase Inhibitors
Proto-Oncogene Proteins c-bcl-2
Thiosemicarbazones
bcl-2-Associated X Protein
ErbB Receptors
Thiourea