Enzyme Inhibitors from Gorgonians and Soft Corals

Abstract

For decades, gorgonians and soft corals have been considered promising sources of bioactive compounds, attracting the interest of scientists from different fields. As the most abundant bioactive compounds within these organisms, terpenoids, steroids, and alkaloids have received the highest coverage in the scientific literature. However, enzyme inhibitors, a functional class of bioactive compounds with high potential for industry and biomedicine, have received much less notoriety. Thus, we revised scientific literature (1974-2022) on the field of marine natural products searching for enzyme inhibitors isolated from these taxonomic groups. In this review, we present representative enzyme inhibitors from an enzymological perspective, highlighting, when available, data on specific targets, structures, potencies, mechanisms of inhibition, and physiological roles for these molecules. As most of the characterization studies for the new inhibitors remain incomplete, we also included a methodological section presenting a general strategy to face this goal by accomplishing STRENDA (Standards for Reporting Enzymology Data) project guidelines.

Keywords: STRENDA guidelines; enzyme inhibitors; enzyme kinetics; gorgonian; inhibitor characterization; natural products; soft coral.

Figure 1

Distribution of the reviewed enzyme inhibitors isolated from soft corals and gorgonians. Inhibitors were classified according to their organism of origin (A), publication date (B), principal classes of targeted enzymes (C), and molecular structure (D).

Figure 2

PTP1B inhibitors isolated from soft corals and gorgonians (compounds 1–28).

Figure 3

Hydrolase inhibitors isolated from soft corals and gorgonians (compounds 29–44). Structures include inhibitors of acetylcholinesterase, HIV-1 protease, Elastase, and 3CLpro.

Figure 4

Inhibitors of the ubiquitin–proteasome system isolated from soft corals and gorgonians (compounds 45–59).

Figure 5

Phosphodiesterase-4 inhibitors isolated from soft corals and gorgonians (compounds 60–73).

Figure 6

Hydrolase inhibitors isolated from soft corals and gorgonians (compounds 74–82). Structures include inhibitors of α-glucosidase, Histone deacetylase 6 and Phospholipase A2.

Figure 7

Oxidoreductase inhibitors isolated from soft corals and gorgonians (compounds 83–91). Structures include inhibitors of 5α-Reductase, Cytochrome P450 1A, and Tyrosinase.

Figure 8

Transferase inhibitors isolated from soft corals and gorgonians (compounds 92–100). Structures include inhibitors of Tyrosine kinase p56^lck, IKKbeta kinase, EGFR kinase, and protein kinase C.

Figure 9

Transferase inhibitors isolated from soft corals and gorgonians (compounds (101–119). Structures include inhibitors of human tumor-related protein kinases, Casitas B-lineage lymphoma proto-oncogene B, Farnesyl Protein Transferase, and Glutathione S-transferase.

Figure 10

H(+)-pyrophosphatase inhibitors isolated from soft corals and gorgonians (compounds 120–124).

Figure 11

Proposed strategy for the characterization of reversible enzyme inhibitors from marine organisms according to STRENDA guidelines. The strategy is presented as a flowchart with five sequential steps. As alternative approaches or methodologies are possible in each step, two specific sequences are proposed according to the properties of the inhibitor (e.g., classic, rapid reversible inhibitor vs. tight-binding, slow reversible inhibitor).