Title:Chemistry and Anticancer Activity of Hybrid Molecules and Derivatives based on 5-Fluorouracil
Volume: 28
Issue: 27
关键词:
5-氟尿嘧啶、癌症、抗癌活性、混合化合物、共轭物、构效关系 (SAR)。
摘要:
Considering that cancer continues to be an important cause of death worldwide,
several conventional anticancer treatments are widely used. However, most of them
display low selectivity against malignant cells and induce many adverse side effects.
Among these, the use of therapies based on 5-Fluorouracil (5-FU) has been one of the
most efficient, with a broad-spectrum. Due to these circumstances, various modifications
of 5-FU have been developed to improve drug delivery and reduce side effects. Among
the optimization strategies, modifications of 5-FU at N1 or N3 position are made, usually
including the incorporation of pharmacologically active compounds with anticancer activity
(called hybrid molecule) and functionalization with other groups of compounds (called
conjugates).
Several studies have been conducted in the search for new alternative therapies against
cancer. Many of them have evidenced that hybrid compounds exhibit good anticancer activity,
which has emerged as a promising strategy in this field of drug discovery and development.
Furthermore, the binding of 5-FU to amino acids, peptides, phospholipids,
polymers, among others, improves metabolic stability and absorption.
This review highlights the potential of hybrids and derivatives based on 5-FU as a scaffold
for the development of antitumor agents. Besides, it also presents a detailed description
of the different strategies employed to design and synthesized these compounds, together
with their biological activities and structure-activity relationship (SAR) analysis.