Design and Synthesis of Thiourea-Conjugating Organic Arsenic D-Glucose with Anticancer Activities
Boqiao Fu,
Wenxuan Liu,
Yufeng Wang,
Guorui Li,
Yingsha Wang,
Xinyuan Huang,
Hongan Shi,
Caiqin Qin
Affiliations
Boqiao Fu
College of Chemistry and Materials Science, Hubei Engineering University, Xiaogan 432000, China
Wenxuan Liu
College of Chemistry and Materials Science, Hubei Engineering University, Xiaogan 432000, China
Yufeng Wang
College of Chemistry and Materials Science, Hubei Engineering University, Xiaogan 432000, China
Guorui Li
Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, the “Double-First Class” Application Characteristic Discipline of Hunan Province (Pharmaceutical Science), Changsha Medical University, Changsha 410219, China
Yingsha Wang
State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, School of Biomedical Sciences, Hunan University, Changsha 410082, China
Xinyuan Huang
Hubei Key Laboratory of Quality Control of Characteristic Fruits and Vegetables, College of Life and Technology, Hubei Engineering University, Xiaogan 432000, China
Hongan Shi
Hubei Key Laboratory of Quality Control of Characteristic Fruits and Vegetables, College of Life and Technology, Hubei Engineering University, Xiaogan 432000, China
Caiqin Qin
College of Chemistry and Materials Science, Hubei Engineering University, Xiaogan 432000, China
Organic arsenic compounds such as p-aminophenylarsine oxide (p-APAO) are easier for structural optimization to improve drug-like properties such as pharmacokinetic properties, therapeutic efficacy, and target selectivity. In order to strengthen the selectivity of 4-(1,3,2-dithiarsinan-2-yl) aniline 7 to tumor cell, a thiourea moiety was used to strengthen the anticancer activity. To avoid forming a mixture of α/β anomers, the strategy of 2-acetyl’s neighboring group participation was used to lock the configuration of 2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl isothiocyanate from 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide. 1-(4-(1,3,2-dithiarsinan-2-yl) aniline)-2-N-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranos-1-yl)-thiourea 2 can increase the selectivity of human colon cancer cells HCT-116 (0.82 ± 0.06 μM vs. 1.82 ± 0.07 μM) to human embryonic kidney 293T cells (1.38 ± 0.01 μM vs. 1.22 ± 0.06 μM) from 0.67 to 1.68, suggesting a feasible approach to improve the therapeutic index of arsenic-containing compounds as chemotherapeutic agents.
