Therapeutic Potential of Nitrogen Mustard Based Hybrid Molecules

Abstract

As medicine advances, cancer is still among one of the major health problems, posing significant threats to human health. New anticancer agents features with novel scaffolds and/or unique mechanisms of action are highly desirable for the treatment of cancers, especially those highly aggressive and drug-resistant ones. Nitrogen mustard has been widely used as an anticancer drug since the discovery of its antitumor effect in the 1942. However, the lack of selectivity to cancer cells restricts the wide usage of a mass of nitrogen mustard agents to achieve further clinical significance. Discovery of antitumor hybrids using nitrogen mustards as key functional groups has exhibited enormous potential in the drug development. Introduction of nitrogen mustards resulted in improvement in the activity, selectivity, targetability, safety, pharmacokinetics and pharmacodynamics properties of corresponding lead compounds or agents. Herein, the recently developed nitrogen mustard based hybrids have been introduced in the cancer therapy.

Keywords: antitumor; drug discovery; hybrids; nitrogen mustard; side effects.

FIGURE 1

Origin of nitrogen mustards.

FIGURE 2

Representative nitrogen mustard agents.

FIGURE 3

Structures of Brefeldin A-nitrogen mustard hybrids.

FIGURE 4

Structures of evodiamine-nitrogen mustard hybrids.

FIGURE 5

Structures of oridonin-nitrogen mustard hybrids.

FIGURE 6

Structures of sophoridine-nitrogen mustard hybrids.

FIGURE 7

Structures of etoposide-nitrogen mustard hybrids.

FIGURE 8

Structures of steroid-nitrogen mustard hybrids.

FIGURE 9

Structures of Tyrosine-nitrogen mustard hybrids.

FIGURE 10

Structure of Platinum-nitrogen mustard hybrid.

FIGURE 11

Structures of melamine-nitrogen mustard hybrids.

FIGURE 12

Structures of IDO1-nitrogen mustard hybrids.

FIGURE 13

Summary of the nitrogen mustard based hybridization strategy involved in the current article.