Natural Products as Inhibitors of DNA Related Enzymes

Pungitore, Carlos Rodolfo

doi:10.2174/157340808786733604

Cited by 7 publications

(10 citation statements)

References 78 publications

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“…For example, it has been postulated that fatty acids, such as palmitic acid, play a key role in regulating the characteristic loss of homeostasis in cancer [4]. Numerous fatty acids, mainly of bacterial origin, also inhibit DNA polymerase and Topoisomerase I, and display anti-malarial and anti-viral activity [1, 7-11]. …”

Section: Introductionmentioning

confidence: 99%

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The (5Z)‐5‐Pentacosenoic and 5‐Pentacosynoic Acids Inhibit the HIV‐1 Reverse Transcriptase

Moreira

Orellano

Rosado

et al. 2015

Lipids

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The natural fatty acids (5Z)-5-pentacosenoic and (9Z)-9-pentacosenoic acids were synthesized for the first time in eight steps starting from either 4-bromo-1-butanol or 8-bromo-1-butanol and in 20-58% overall yields, while the novel fatty acids 5-pentacosynoic and 9-pentacosynoic acids were also synthesized in six steps and in 34-43% overall yields. The Δ5 acids displayed the best IC50’s (24-38 µM) against the HIV-1 reverse transcriptase (RT) enzyme, comparable to nervonic acid (IC50 = 12 µM). The Δ9 acids were not as effective towards HIV-RT with the (9Z)-9-pentacosenoic acid displaying an IC50 = 54 µM. Fatty acid chain length and position of the unsaturation was critical for the observed inhibition. Molecular modeling studies indicated the structural determinants underlying the biological activity of the most potent compounds. These results provide new insights into the structural requirements that must be present in fatty acids so as to enhance their inhibitory potential towards HIV-RT.

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Section: Introductionmentioning

confidence: 99%

“…It is still necessary to develop new less cytotoxic antiretrovirals for the treatment of this disease. Natural products from various marine sources have been known to possess diverse biological activities including antiviral [11, 31]. …”

Section: Introductionmentioning

confidence: 99%

The (5Z)‐5‐Pentacosenoic and 5‐Pentacosynoic Acids Inhibit the HIV‐1 Reverse Transcriptase

Moreira

Orellano

Rosado

et al. 2015

Lipids

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“…As part of a programme to determine biological activities of natural products and derivatives (Pungitore 2008; Martin et al 2011; Garro et al 2015), 17 alkaloids previously reported were tested as biofilm forming inhibitors (Fig. 1) (Di Marco et al 2019).…”

Section: Methodsmentioning

confidence: 99%

Aporphinoid alkaloids inhibit biofilm formation of Yersinia enterocolitica isolated from sausages

Marco

Pungitore

Estrada

2020

J. Appl. Microbiol.

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Aims of the study The ability of Yersinia enterocolitica strains to form biofilms and the capacity of different alkaloids to inhibit biofilm formation were investigated. Methods and Results The capacity to form biofilm on polystyrene of 31 Y. enterocolitica strains was evaluated. Biofilm and quorum sensing (QS) inhibition of 17 alkaloids were assayed; furthermore, minimum biofilm inhibitory concentration (MBIC) was determined. The capacity to form biofilms among the examined strains seemed to be a strain‐related feature. The best biofilm inhibitors at 100 µmol l−1 were oliverine (1), guatterine (3), liriodenine (4), oliveridine (5) and pachypodanthine (6), which showed biofilm inhibition higher than 87%. Pachypodanthine (6) was the most effective compound with MBIC value of 12·5 µmol l−1 at subinhibitory concentration and also was able to inhibit QS system and reduce yenR expression at this concentration. Conclusion This is the first study to demonstrate that oliverine, liriodenine, and pachypodanthine are able to inhibit biofilm formation of Y. enterocolitica without critically disturbing its growing capacity. At MBIC, pachypodanthine inhibited biofilm formation and QS. Significance and Impact of the Study The use of aporphinoid alkaloids as biofilms inhibitory agents might potentially be useful to treat biofilm‐associated infections in the future.

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“…The finding and development of new lead compounds are a consequence of the rapid growth in the discovery of molecular targets that may be applied to the discovery of novel tools for diagnosis, prevention and treatment of human diseases. DNA polymerases (DNA pols), topoisomerases (Topos) and reverse transcriptase (RT) enzymes have recently emerged as important molecular targets for the development of anticancer and anti-viral agents [1][2].…”

Section: Introductionmentioning

confidence: 99%

Natural Products, Synthetic and Non-Nucleoside Compounds as Inhibitors of Enzymes Related to DNA: Update 2013

Pungitore

2014

CEI

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This review article tries to be an update of 2008 Pungitore's review. Again, this paper tries to summarize the investigation about natural products, synthetic and non-nucleoside compounds with the ability to inhibit enzymes that play a crucial role in DNA metabolism such as replication, transcription, retro-transcription, recombination, and chromosome segregation during mitosis. The focus is placed on DNA polymerases, topoisomerases and reverse transcriptase inhibitors because most of the literature emphasized on their inhibitory activity. A great diversity of chemical compounds encompassing triterpenes, flavonoids, chromones, lipids, iridoids, phytosterols, coumarins, anthracyclines, quinones, protoberberines, tannins, lignans, acetogenins, benzimidazoles and other natural products, produced by different species of organisms, have inhibitory activities against enzymes related to DNA metabolism allowing these enzymes to arise as important molecular targets for cancer and AIDS research.

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Natural Products as Inhibitors of DNA Related Enzymes

Cited by 7 publications

References 78 publications

The (5Z)‐5‐Pentacosenoic and 5‐Pentacosynoic Acids Inhibit the HIV‐1 Reverse Transcriptase

The (5Z)‐5‐Pentacosenoic and 5‐Pentacosynoic Acids Inhibit the HIV‐1 Reverse Transcriptase

Aporphinoid alkaloids inhibit biofilm formation of Yersinia enterocolitica isolated from sausages

Natural Products, Synthetic and Non-Nucleoside Compounds as Inhibitors of Enzymes Related to DNA: Update 2013

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