Relevance of Fluorinated Ligands to the Design of Metallodrugs for Their Potential Use in Cancer Treatment

Abstract

Fluorination of pharmaceutical agents has afforded crucial modifications to their pharmacological profiles, leading to important advances in medicinal chemistry. On the other hand, metallodrugs are considered to be valuable candidates in the treatment of several diseases, albeit with the caveat that they may exhibit pharmacological disadvantages, such as poor water solubility, low bioavailability and short circulating time. To surmount these limitations, two approaches have been developed: one based on the design of novel metallodrug-delivering carriers and the other based on optimizing the structure of the ligands bound to the metal center. In this context, fluorination of the ligands may bring beneficial changes (physicochemical and biological) that can help to elude the aforementioned drawbacks. Thus, in this review, we discuss the use of fluorinated ligands in the design of metallodrugs that may exhibit potential anticancer activity.

Binuclear platinum(ii) complexes bearing various bridging 1,1′-diphosphinoferrocene ligands as potential anticancer agents: synthesis and biological evaluation

“…[39][40][41] Also, fluorinated compounds increase their lipophilicity and membrane penetration. 42,43 The pharmacological properties and cellular absorption of drugs are determined by several parameters in medicinal chemistry. It is essential for most pharmacokinetic processes that drugs pass across the cell membranes.…”

Experimental Murine Models for Colorectal Cancer Research

“…The C57BL/6-derived adenocarcinoma line MC38 and the Balb/c-derived lymphoma line CT26 are commonly used in studies of syngeneic s.c. transplantation [160]. Due to their high mutation rates, these cells have been proven to be effective preclinical models of human tumors; however, the success of orthotopic engraftment of MC38 tumors has Concerning human cell lines, HCT-116 is one of the most popular CRC cell lines [117,[164][165][166][167][168][169][170][171][172][173][174][175][176]. Beside HCT-116 cell line, several other cell lines are utilized in CRC research, such as HT-29 [3,[177][178][179][180][181][182], SW620 [183][184][185][186], T84 [179,187], LoVo [188,189], LS174T [190][191][192][193], DLD-1 [194][195][196][197], and SW480 [85,146,188].…”

The Impact of Fluorination on the Design of Histone Deacetylase Inhibitors

“…Fluorination is another very common method of fine-tuning drug molecules [ 22 , 23 , 24 ]. This concerns, for instance, the development of glycomimetic drugs [ 25 ], metal complexes [ 26 ], and nucleosides [ 27 ], with all of these exerting also anticancer activity. The introduction of fluorine substituents in antitumor active compounds is performed for various reasons, such as bioanalytical labeling, in order to increase selectivity [ 28 ] or regulate the mechanism of cell death [ 29 ].…”