Synthesis and evaluation of the mutagenicity of 3-alkylpyridine marine alkaloid analogues with anticancer potential

Barbosa, Maria Cristina S.; Barbosa, Camila de Souza; Oliveira, Jorge de; Moreira, Natália; Martins, Natália Rezende de Miranda; Gomes, Gabrielle Kéfrem Alves; Caldeira, Camila A.; Costa, Marília Ladeira Alves e; Guimarães, Daniel Silqueira Martins; Guimarães, Luciana; Nascimento, Clébio S.; Varotti, Fernando de Pilla; Viana, Gustavo Henrique Ribeiro; Santos, Fábio V.

doi:10.1016/j.mrgentox.2017.11.006

Cited by 15 publications

(6 citation statements)

References 44 publications

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“…An important limitation for the use of alkaloids is their high cytotoxicity, which has already been described in another study (Barbosa et al 2018). Thus, the main challenge for the development of new antifungals is related to the fact that both fungi and human cells are eukaryotic, making it challenging to identify specific metabolite targets and fungal structures, which results in the high toxicity of antifungal agents (Morace et al 2014, Andrade et al 2018).…”

Section: Resultsmentioning

confidence: 84%

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Antifungal activity of a novel 3-Alkylpyridine analog derived from Marine sponge alkaloids

Andrade

Lima

Barbosa

et al. 2021

An. Acad. Bras. Ciênc.

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Section: Resultsmentioning

confidence: 84%

“…The synthesis of 3-APA analogs of theonelladin C (compounds 1, 2a-d, 3, and 4) (Figure 1) was performed as previously described by Hilário et al (2011), Gonçalves et al (2014), andBarbosa et al (2018).…”

Section: Synthesismentioning

confidence: 99%

Antifungal activity of a novel 3-Alkylpyridine analog derived from Marine sponge alkaloids

Andrade

Lima

Barbosa

et al. 2021

An. Acad. Bras. Ciênc.

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“…In another study, alkaloids synthesized from molecular structures from sponge Theonella sp. showed anti‐malarial activity, although they did not present the necessary selectivity (Barbosa et al, ). The synthesized alkaloids were evaluated for their mutagenic and genotoxic potential through in vitro micronucleus, comet, Ames, and annexin V ‐ propidium iodide tests to understand mechanisms responsible for the associated toxicity.…”

Section: Discussionmentioning

confidence: 99%

Mutagenic, genotoxic and cytotoxic studies of invasive corals Tubastraea coccinea and Tubastraea tagusensis

Carpes

Alves

Creed

et al. 2019

J of Applied Toxicology

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The high diversity of species in the marine environment gives rise to compounds with unique structural patterns not found as natural products in other systems and with great potential for pharmacological, cosmetic and nutritional use. The genus Tubastraea (Class Anthozoa, Order Scleractinia, Family Dendrophylliidae) is characterized as a hard coral without the presence of zooxanthellae. In species of this genus alkaloids derived from the compound aplysinopsin with pharmacological activity are known. In Brazil T. coccinea and T. tagusensis are characterized as non‐indigenous and invasive and are currently found along the Brazilian coast, from Santa Catarina to Bahia states. This study aims to analyze the mutagenic, cytotoxic and genotoxic potential of methanolic and ethanolic extracts from T. coccinea and T. tagusensis collected in Ilha Grande Bay, Rio de Janeiro state, Brazil. Bacterial reverse mutation assay on the standard strains TA97, TA98, TA100, TA102 and TA104, in vitro micronucleus formation test and colorimetric assays for cytotoxic signals on the cell lines HepG2 and RAW264.7 were used. We also synthesized an oxoaplysinopsin derivate alkaloid (APL01) for comparative purposes. No mutagenic (250; 312.5; 375; 437.5 and 500 μg/plate) or genotoxic (0.05; 0.5; 5.0; 50 and 500 μg/mL) effects were observed in any sample tested for all measured concentrations. Cytotoxic responses were observed for eukaryotic cells in all tested samples at 500 and 5000 μg/mL concentrations. Cytotoxicity found in the WST‐1 assay was independent of the metabolism of substances present in samples compositions. The cytotoxicity observed in the LDH release assay depended on metabolism.

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“…belongs to the order Lithistida, which is characterized by a hard skeleton comprised of interlocking spicules of silica [ 4 ]. The sponge is globally distributed and contains a variety of metabolites with cytotoxic activity including 4-methylene steroids [ 5 ], nucleosides [ 6 ], macrolides [ 7 , 8 , 9 ], cyclopeptides [ 10 , 11 , 12 ], cyclodepsipeptides [ 13 , 14 ], linear peptides [ 15 ], and alkaloids [ 16 , 17 ]. The 4-methylene steroids, characterized by an exocyclic double bond at C-4, were exclusively identified from the genus Theonella , suggesting their potential use as chemotaxonomic markers [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-Proliferative Potential of Secondary Metabolites from the Marine Sponge Theonella sp.: Moving from Correlation toward Causation

Lai

Peng

et al. 2021

Metabolites

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Marine sponges have been recognized as a rich source of potential anti-proliferative metabolites. Currently, there are two sponge-derived anti-cancer agents (a macrolide and a nucleoside) isolated from the Porifera phylum, suggesting the great potential of this sponge as a rich source for anti-neoplastic agents. To search for more bioactive metabolites from this phylum, we examined the EtOAc extract of Theonella sp. sponge. We isolated seven compounds (1–7), including four 4-methylene sterols (1–4), two nucleosides (5 and 6), and one macrolide (7). Among them, theonellasterol L (1) was identified for the first time, while 5′-O-acetyl-2′-deoxyuridine (5) and 5′-O-acetylthymidine (6) were the first identified deoxyuridine and thymidine derivatives from the sponge Theonella sp. These structures were elucidated based on their spectroscopic data. The anti-proliferation activity of compounds 1–7 against the MCF-7, MDA-MB-231, T-47D, HCT-116, DLD-1, K562, and Molt 4 cancer cell lines was determined. The results indicated that the 14-/15-oxygenated moiety played an important role in the antiproliferative activity and the macrolide derivatives dominated the anti-proliferative effect of the sponge Theonella sp. The in silico analysis, using a chemical global positioning system for natural products (ChemGPS-NP), indicated an anti-proliferative mode of actions (MOA) suggesting the potential applications of the isolated active metabolites as anti-proliferative agents.

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Synthesis and evaluation of the mutagenicity of 3-alkylpyridine marine alkaloid analogues with anticancer potential

Cited by 15 publications

References 44 publications

Antifungal activity of a novel 3-Alkylpyridine analog derived from Marine sponge alkaloids

Antifungal activity of a novel 3-Alkylpyridine analog derived from Marine sponge alkaloids

Mutagenic, genotoxic and cytotoxic studies of invasive corals Tubastraea coccinea and Tubastraea tagusensis

Anti-Proliferative Potential of Secondary Metabolites from the Marine Sponge Theonella sp.: Moving from Correlation toward Causation

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