Small Molecules of Marine Origin as Potential Anti-Glioma Agents

Abstract

Marine organisms are able to produce a plethora of small molecules with novel chemical structures and potent biological properties, being a fertile source for discovery of pharmacologically active compounds, already with several marine-derived agents approved as drugs. Glioma is classified by the WHO as the most common and aggressive form of tumor on CNS. Currently, Temozolomide is the only chemotherapeutic option approved by the FDA even though having some limitations. This review presents, for the first time, a comprehensive overview of marine compounds described as anti-glioma agents in the last decade. Nearly fifty compounds were compiled in this document and organized accordingly to their marine sources. Highlights on the mechanism of action and ADME properties were included. Some of these marine compounds could be promising leads for the discovery of new therapeutic alternatives for glioma treatment.

Keywords: drug discovery; glioma; marine compound.

Figure 1

(A)—Temozolomide (TMZ); (B)—3-methyl-(triazen-1-yl)imidazole-4-carboxamide (MTIC).

Figure 2

Synthetic compounds that have shown in vivo efficacy against GBM.

Figure 3

Compounds 1–6 isolated from the culture of Streptomyces sp. ZZ406 [40].

Figure 4

Sesquiterpene 7 isolated from marine red seaweed [44].

Figure 5

Compounds 8–10 isolated from brown seaweed [41,45].

Figure 6

Bafilomycins 11–14 isolated from marine green algae Ulva pertusa [43].

Figure 7

Actinomycins 15–17 isolated from sea squirts [37].

Figure 8

Fradimicins 18 and 19 isolated from Streptomyces fradiae PTZ0025 [47].

Figure 9

Streptoglutarimides 20 and 21 isolated from Actinomycete Derivates Streptomyces sp. ZZ741 [48].

Figure 10

Antraquinone 22 isolated from the marine Echinoderm Comanthus sp [49].

Figure 11

Alkaloids 23–25 isolated from Thai marine invertebrates [50].

Figure 12

Alkaloids 26–28 isolated from Marine Sponge Corticium sp. [51].

Figure 13

Plakortide 29 isolated from Marine Sponge Plakortis halichondroides [52].

Figure 14

Sesquiterpenes 30–38 isolated from extracts of the Hawaiian marine sponge Dactylospongia elegans [53].

Figure 15

Sphingosine 39 isolated from a marine sponge Haliclona tubifera [54].

Figure 16

Polyketides 40–46 isolated from Caribbean Octocoral Eunicea succinea [52].

Figure 17

Alkaloid 47 isolated from marine fungus strain ZZ380 [55].

Figure 18

Sulfated saponins 48–50 isolated from Cucumber Holothuria moebii [56].

Figure 19

Astaxanthin (51) Adonixanthin (52) isolated from a red pigment [57].

Figure 20

Marine organisms as sources of anti-glioma compounds.

Figure 21

Most significant chemical classes of anti-glioma compounds.