Synthesis and characterization of novel polyamine sulphur analogues and its effects on cancer cell proliferation

Abstract

Natural polyamines such as putrescine, spermidine, and spermine are crucial for cell growth and proliferation. However, over accumulation of polyamines can lead to the worst scenario which is the progression of cancer cells. The upregulation of polyamine transport system (PTS) activity leads to an opportunity to develop more specific and effective cancer treatment. Researches in compound containing sulphur and the polyamine transport system is beneficial in oncology as both affect cancer cells. Compounds containing sulphur such as organo sulphur are known for its anti-cancer properties. Recent studies revealed, several new compounds were successfully synthesized to combat cancer cells. Some of the compounds that were successfully synthesized were the polyamine-sulphur compounds. By adding sulphur to known natural polyamine, the analogues will be delivered specifically to cancer cells via polyamine transport system (PTS). For the synthesis of the compound, carbon disulphide and benzyl chloride were added to the polyamine (Putrescine or Spermidine) via a method called Room Temperature Mediated Synthesis. The addition of carbon disulphide was to add the sulphur element while the addition of benzyl chloride was to make the compound bulkier and stable. The analogues were named and categorized based on the starting material. The analogues named PSA-1 and SSA-1 are the analogues that were created by synthesizing the starting materials (putrescine and spermidine) with carbon disulphide only. For the addition of both carbon disulphide and benzyl chloride, the analogues were named PSA-2 and SSA-2. The resulting analogues were analyzed by using Fourier Transformed Infrared Spectroscopy (FTIR) and Gas Chromatography-Mass Spectroscopy (GC-MS) to determine the successful addition of sulphur and benzyl compound. In addition, the compounds were then tested with human lung adenocarcinoma cells (A549), human breast adenocarcinoma cell (MCF-7) and human colorectal adenocarcinoma cells (HCT-8). The cytotoxicity effects of these compounds were determined by using MTT assay technique against these in-vitro cells. The results show the cytotoxic effects were not potent against these cell lines as a higher concentration of compounds were needed to inhibit the cells growth.