Design and synthesis of novel N()-substituted thiosemicarbazones bearing a pyrrole unit as potential anticancer agents

Taofeng Zhu; Shanshan Shen; Qin Lu; Xingpei Ye; Weiliang Ding; Ruhua Chen; Jing Xie; Wenjiao Zhu; Jun Xu; Lei Jia; Weina Wu; Tieliang Ma

doi:10.3892/ol.2017.5995

Design and synthesis of novel N()-substituted thiosemicarbazones bearing a pyrrole unit as potential anticancer agents

Oncol Lett. 2017 Jun;13(6):4493-4500. doi: 10.3892/ol.2017.5995. Epub 2017 Apr 5.

Authors

Taofeng Zhu^{1

2}, Shanshan Shen³, Qin Lu¹, Xingpei Ye⁴, Weiliang Ding⁵, Ruhua Chen¹, Jing Xie⁶, Wenjiao Zhu⁵, Jun Xu⁴, Lei Jia⁴, Weina Wu⁴, Tieliang Ma⁵

Affiliations

¹ Department of Respiratory Disease, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
² Department of Respiratory Disease, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu 214200, P.R. China.
³ Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
⁴ Department of Physics and Chemistry, College of Chemistry and Chemical Engineering, Henan Polytechnic University, Jiaozuo, Henan 454000, P.R. China.
⁵ Central Laboratory, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu 214200, P.R. China.
⁶ Department of Geriatrics, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu 214200, P.R. China.

Abstract

A series of N(4)-substituted thiosemicarbazones (TSCs) bearing pyrrole unit (1a-1e) were synthesized and fully characterized by elemental analyses, infrared spectra, ¹H nuclear magnetic resonance and single crystal X-ray diffraction. The compounds were assessed as potential chemotherapeutic agents. All newly synthesized compounds were screened for their anticancer activity against lung cancer PC-9, esophageal cancer Eca-109 and gastric cancer SGC-7901 cell lines. The results of MTT, Terminal deoxynucleotidyl transferase dUTP nick end labeling and fluorescence-activated cell sorting assays indicated that all the prepared compounds exhibited cytotoxicity against PC-9, Eca-109 and SGC-7901 cells in vitro. All the compounds significantly induced cancer cell apoptosis accompanied by increasing the Bax/Bcl-2 ratio and activation of caspase-3. The structure-activity association was discussed and the potential pre-clinical trials may be conducted. The present findings have a great potential in biomedical applications of novel N(4)-substituted TSCs.

Keywords: cytotoxic; pyrrole; thiosemicarbazone.