Antitumor compounds from marine actinomycetes

Abstract

Chemotherapy is one of the main treatments used to combat cancer. A great number of antitumor compounds are natural products or their derivatives, mainly produced by microorganisms. In particular, actinomycetes are the producers of a large number of natural products with different biological activities, including antitumor properties. These antitumor compounds belong to several structural classes such as anthracyclines, enediynes, indolocarbazoles, isoprenoides, macrolides, non-ribosomal peptides and others, and they exert antitumor activity by inducing apoptosis through DNA cleavage mediated by topoisomerase I or II inhibition, mitochondria permeabilization, inhibition of key enzymes involved in signal transduction like proteases, or cellular metabolism and in some cases by inhibiting tumor-induced angiogenesis. Marine organisms have attracted special attention in the last years for their ability to produce interesting pharmacological lead compounds.

Keywords: anthracycline; indolocarbazole; macrolide; non-ribosomal peptide synthetase; polyketide synthase.

Figure 1

Polyketide compounds arenicolides and saliniketals produced by S. arenicola CNR-005 and other macrolides and macrolactams.

Figure 2

Structures of marinomycins.

Figure 3

Structures of manumycin type compounds and lissoclinolide.

Figure 4

Structures of salinipyrones, pacificanones, sporolides, actinofuranones, cyanosporasides and piericidins type I polyketides and nonactin type II polyketide.

Figure 5

Structures of several anthracyclines and anthracycline-like compounds.

Figure 6

Structures of anthraquinone and quinone-related compounds.

Figure 7

Structures of angucyclines and related compounds.

Figure 8

Structures of proximicins, lucentamycins and mechercharmycins.

Figure 9

Structures of depsipeptides thiocoraline, arenamides and piperazimycins.

Figure 10

Structures of mixed polyketide/non-ribosomal peptide compounds.

Figure 11

Structures of monoterpenes and sesquiterpenes isolated from marine actinomycetes.

Figure 12

Structures of chlorinated dihydroquinones and active compound from strain MS1/7.

Figure 13

Structures of indocarbazoles and bisindole pyrroles produced by marine actinomycetes.

Figure 14

Structures of polypyrrole, tetrahydropyrrole, pyrroloiminoquinone and pyrrolizidine compounds.

Figure 15

Structure of indole, benzoxazole, methylpiridine and butenolide compounds.

Figure 16

Structures of phenazine, phenoxazin-3-one and tricyclic acetal-lactone compounds.