Aromatase Inhibitors as a Promising Direction for the Search for New Anticancer Drugs

Abstract

Aromatase is an enzyme that plays a crucial role in the biosynthesis of estrogens, which are hormones that contribute to the growth of certain types of breast cancer. In particular, aromatase catalyzes the conversion of androgens (male hormones) into estrogens (female hormones) in various tissues, including the adrenal glands, ovaries, and adipose tissue. Given the role of estrogen in promoting the growth of hormone-receptor-positive breast cancers, aromatase has become an important molecular target for the development of anticancer agents. Aromatase inhibitors can be classified into two main groups based on their chemical structure: steroidal and non-steroidal inhibitors. This work presents a review of the literature from the last ten years regarding the search for new aromatase inhibitors. We present the directions of search, taking into account the impact of structure modifications on anticancer activity.

Keywords: anticancer activity; aromatase inhibitors; steroidal and non-steroidal compounds.

Figure 1

Chemical structures of newly approved aromatase inhibitor elacestrant and early approved aromatase inhibitors used in the combined clinical trials with kinase inhibitors in the period of 2013–2023.

Figure 2

PRISMA flow chart for systematic review [11].

Figure 3

Novel steroidal aromatase inhibitors.

Figure 4

Examples of new potential aromatase inhibitors with steroidal scaffolds.

Figure 5

Novel steroidal aromatase inhibitors.

Figure 6

New steroidal molecules as possible aromatase inhibitors.

Figure 7

Potential aromatase inhibitors with imidazole scaffolds.

Figure 8

Potential aromatase inhibitors with benzimidazole scaffolds.

Figure 9

Potential aromatase inhibitors with triazole scaffolds.

Figure 10

Potential aromatase inhibitors with triazole scaffolds as analogs of approved drugs.

Figure 11

Coumarin-based and coumarin/chromone/heterocycle-bearing hybrid molecules as potential aromatase inhibitors.

Figure 12

Potential aromatase inhibitors with benzofuran and benzothienopyrimidine scaffolds.

Figure 13

Potential aromatase inhibitors with privileged heterocyclic scaffolds.

Figure 14

Potential aromatase inhibitors with aryl/hetarylhydrazone moiety in molecules.

Figure 15

Sulfonyl/amide-containing molecules and thioureas as potential aromatase inhibitors.

Figure 16

Triphenylethylene derivatives as potential aromatase inhibitors.