Synthesis, Characterization and Preliminary Anticancer Study of Novel 5-fluorouracil Conjugate with Pyrrolidine Dithiocarbamate as a Mutual Anticancer Prodrug

• Main Authors: Ikram K. Shihab (Author), Mohammed H. Mohammed (Author)
• Format: Book
• Published: College of Pharmacy University of Baghdad, 2019-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

 5-Fluorouracil is one of the commonly used chemotherapy drugs in anticancer therapy; unfortunately treatment with 5-FU by solely has many drawbacks  low lipophilicity, low permeability, low molecular weight, and its relatively poor plasma protein binding; also a brief half-life therefore frequent administration is required to maintain the optimal therapeutic plasma level which in addition to its poor selectivity, drug resistance and limited penetration to cancer cells; leads to increased incidence of side-effects to healthy cells/tissues and low response rates. In order to minimize these drawbacks; 5-FU was chemically  conjugated with pyrrolidine dithiocarbamate (PDTC) in a mutual prodrug moiety (S-(9H-purin-6-yl) 3-((pyrrolidine-1-carbonothioyl)thio)propanethioate) "compound [IV]" with (chloroacetic acid) and (chloroethanol) being the linkers ;synthesized prodrug and intermediates were characterized and identified using FTIR ,1H NMR and all the results shown good agreements with the proposed chemical structures of the synthesized compounds.  ; in-vitro preliminary cytotoxicity study was conducted for compound [IV] and 5-FU on CAL 51 and B16V cell lines ,results showed  enhanced cytotoxic effects for [IV] over 5-FU.

Item Description

10.31351/vol28iss2pp17-23
2521-3512
1683-3597