Synthesis, Cytotoxic Effect Assessment and Molecular Docking Studies of Disubstituted Thiadiazole Including Oxadiazole as Hybrid Component

Abstract

Cancer is the second leading cause of death in the world. Due to toxicity and resistance to common therapies, the attempt to develop new anticancer agents has become a major challenge. Oxadiazole and thiadiazole are of interest building blocks used in drug design. Hybrids of thiadiazole- oxadiazole have been synthesized with significant cytotoxic effects. Considering importance of mentioned scaffolds some of the thiadiazole-oxadiazole derivatives were synthesized by three steps in this study. Firstly, thiol function of 2-amino-5-mercapto-1, 3, 4-thiadiazole was alkylated by benzyl chloride derivatives to give compounds (1a-c). The reaction of chloroacetyl chloride with amine group of compounds (1a–c) terminates to amide derivatives (2a-c). Definitive products were produced by treatment of corresponding amide derivatives with 5-(4-chlorophenyl)-1, 3, 4-oxadiazole-2-thiol. Synthesized compounds were evaluated by MTT assay against three cell lines. The final molecules were docked in the active sites of the epidermal growth factor receptor tyrosine kinase to assay the possible interactions. Final products showed range of cytotoxic activity of moderate to good against tested cell lines. Compound (3a) demonstrated a higher cytotoxic activity against MCF-7 (IC50: 26 μM) and Lncap (IC50: 37 μM) cell lines in comparison with other compounds. The highest docking score was -10.55 kcal/mol for compound 3a.

Keywords

• Cytotoxic
• Docking
• Synthesis
• Oxadiazol
• Thiadiazole
• MTT assay

Synthesis, Cytotoxic Effect Assessment and Molecular Docking Studies of Disubstituted Thiadiazole Including Oxadiazole as Hybrid Component

Abstract

Cancer is the second leading cause of death in the world. Due to toxicity and resistance to common therapies, the attempt to develop new anticancer agents has become a major challenge. Oxadiazole and thiadiazole are of interest building blocks used in drug design. Hybrids of thiadiazole- oxadiazole have been synthesized with significant cytotoxic effects. Considering importance of mentioned scaffolds some of the thiadiazole-oxadiazole derivatives were synthesized by three steps in this study. Firstly, thiol function of 2-amino-5-mercapto-1, 3, 4-thiadiazole was alkylated by benzyl chloride derivatives to give compounds (1a-c). The reaction of chloroacetyl chloride with amine group of compounds (1a–c) terminates to amide derivatives (2a-c). Definitive products were produced by treatment of corresponding amide derivatives with 5-(4-chlorophenyl)-1, 3, 4-oxadiazole-2-thiol. Synthesized compounds were evaluated by MTT assay against three cell lines. The final molecules were docked in the active sites of the epidermal growth factor receptor tyrosine kinase to assay the possible interactions. Final products showed range of cytotoxic activity of moderate to good against tested cell lines. Compound (3a) demonstrated a higher cytotoxic activity against MCF-7 (IC50: 26 μM) and Lncap (IC50: 37 μM) cell lines in comparison with other compounds. The highest docking score was -10.55 kcal/mol for compound 3a.

Keywords

• Cytotoxic
• Docking
• Synthesis
• Oxadiazol
• Thiadiazole
• MTT assay

References

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