Bioactive Marine Xanthones: A Review

Abstract

The marine environment is an important source of specialized metabolites with valuable biological activities. Xanthones are a relevant chemical class of specialized metabolites found in this environment due to their structural variety and their biological activities. In this work, a comprehensive literature review of marine xanthones reported up to now was performed. A large number of bioactive xanthone derivatives (169) were identified, and their structures, biological activities, and natural sources were described. To characterize the chemical space occupied by marine-derived xanthones, molecular descriptors were calculated. For the analysis of the molecular descriptors, the xanthone derivatives were grouped into five structural categories (simple, prenylated, O-heterocyclic, complex, and hydroxanthones) and six biological activities (antitumor, antibacterial, antidiabetic, antifungal, antiviral, and miscellaneous). Moreover, the natural product-likeness and the drug-likeness of marine xanthones were also assessed. Marine xanthone derivatives are rewarding bioactive compounds and constitute a promising starting point for the design of other novel bioactive molecules.

Keywords: antimicrobial; antitumor; drug-like; marine products; molecular descriptors; natural products; xanthone.

Figure 1

Structures of bioactive marine xanthones.

Figure 1

Structures of bioactive marine xanthones.

Figure 1

Structures of bioactive marine xanthones.

Figure 1

Structures of bioactive marine xanthones.

Figure 1

Structures of bioactive marine xanthones.

Figure 1

Structures of bioactive marine xanthones.

Figure 2

Distribution of type (a) microorganism source (b) and activity (c) of the bioactive marine xanthones.

Figure 3

Distribution of MW (a); Fsp³ (b); number of RBs (c); log P (d); TPSA (e); and log S (f) accordingly to the type of xanthone: “simple” (S, blue), “prenylated” (P, green), “hydroxanthone” (H, orange), O-heterocyclic (O, red), and complex (C, purple). Comparison between the values of Fsp³ carbons and MW (g); log P and MW (h); MW and TPSA (i); log P and log S (j); MW and log S (k); TPSA and log S (l).

Figure 4

(a) KDE distribution plot NP-likeness score of synthetic molecules (SM), natural products (NP), and NP-likeness score of marine xanthones. (b) Distribution of NP-likeness score accordingly to the type of xanthone: “simple” (S, blue), “prenylated” (P, green), “hydroxanthone” (H, orange), “O-heterocyclic” (O, red), and “complex” (C, purple). (c) Heatmap of the compliance with rules of drug-likeness for the xanthone types. (d) Distribution of QED index accordingly to the type of xanthone.

Figure 5

Distribution of MW (a); log S (b); log P (c); and fraction of sp³ carbons (d) accordingly to the biological activity reported for marine xanthones: antitumor (AT), antibacterial (AB), antiviral (AV), antifungal (AF), and antidiabetic (AD). Analysis of the functional group frequently found on antitumor (e); antibacterial (f); antiviral (g); antifungal (h), and antidiabetic (i) marine xanthones.

Figure 6

The number of antitumor marine xanthone and the most frequently assayed tumor cell lines. Dark purple bar represents the total count of the assayed xanthones. Light purple bar represents the count of xanthones with IC₅₀ lower than 10 µM.

Figure 7

(a) The number of antibacterial marine xanthones evaluated against Gram-positive and Gram-negative bacteria. Dark blue bar represents the total count of the assayed xanthones. Light blue bar represents the count of xanthones with MIC lower than 4 µg mL⁻¹. (b) The bacteria that were assayed for antibacterial activity. Dark blue bar represents the total count of the assayed xanthones. Light blue bar represents the count of xanthones with MIC lower than 4 µg mL⁻¹.