Risk assessment of Soulatrolide and Mammea (A/BA+A/BB) coumarins from Calophyllum brasiliense by a toxicogenomic and toxicological approach

Gómez-Verján, Juan Carlos; Estrella-Parra, Edgar Antonio; Vázquez-Martínez, Edgar Ricardo; González-Sánchez, Ignacio; Guerrero-Magos, G.; Mendoza-Villanueva, Daniel; Isus, Laura; Alfaro, Ana; Cerbón-Cervantes, Marco Antonio; Aloy, Patrick; Reyes‐Chilpa, Ricardo

doi:10.1016/j.fct.2016.03.010

Cited by 10 publications

(9 citation statements)

References 54 publications

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“…Soulattrolide (Figure ) was isolated by chromatographic methods from the hexane extract of the leaves of C. brasiliense collected in the State of Veracruz, Mexico, and identified by proton and carbon nuclear magnetic resonance, and mass spectrometry, as reported previously (Gomez‐Verjan et al, ; Huerta‐Reyes et al, ).…”

Section: Methodsmentioning

confidence: 84%

“…Soulattrolide is a dipyrano‐tetracyclic coumarin (Figure ) present in the leaves of the tree C. brasilense growing in the Rain Forests of Mexico (Gomez‐Verjan et al, ; Huerta‐Reyes et al, ). In this study, we tested the effects of soulattrolide (Figure ) in several models in mice to assess its antinociceptive, anti‐inflammatory properties, and its possible effects on the CNS.…”

Section: Discussionmentioning

confidence: 99%

“…), and when administered daily at 100 mg/kg p.o. for 1 week showed no tissue damage in liver, kidney, and spleen of mice (Gomez‐Verjan et al, ). However, other effects of soulattrolide remain to be evaluated.…”

Section: Introductionmentioning

confidence: 98%

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Antinociceptive, anti‐inflammatory, and central nervous system (CNS) effects of the natural coumarin soulattrolide

Alonso-Castro

Guzmán-Gutiérrez

Betancourt

et al. 2018

Drug Development Research

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Soulattrolide is a natural coumarin synthesized by the leaves of species of Calophyllum (Calophyllaceae) rain forest trees, including the American C. brasiliense, and the Asian C. teysmanii. Soulattrolide is a potent inhibitor of the reverse transcriptase from HIV‐1 (RT‐HIV‐1), and active against Mycobacterium tuberculosis. However, the effects of this coumarins on other systems, remains to be evaluated. C. brasiliense is used in traditional medicine for the treatment of pain and inflammation. Therefore, we decided to explore the antinociceptive, anti‐inflammatory activity of soulattrolide in mice, as well as, some of its possible effects on the CNS. Soulattrolide showed antinociceptive effects in the writhing test (ED50 = 33.8 mg/kg), as well as, in the formalin test with an ED50 = 7.9, and 22.1 mg/kg for Phases 1 and 2, respectively. The highest dose of soulattrolide (50 mg/kg) induced 40% of antinociception in the hot plate test. Regarding to anti‐inflammatory activity, in the 12‐O‐Tetradecanoylphorbol‐13‐acetate (TPA) test, soulattrolide showed an IC50 = 1.81 μmol/ear, whereas in the myeloperoxidase assay, it showed an inhibition of 87% (1 μmol/ear). Soulattrolide showed sedative effects on the pentobarbital‐induced sleeping time test, and the rotarod test, but lacked antidepressant activity on the tail suspension test. In conclusion, we report for the first time, the antinociceptive effects of soulattrolide in mice, like those of naproxen; soulattrolide also showed mild anti‐inflammatory activity, as well as mild sedative and anxiolytic properties, therefore, it has also activity on the CNS.

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Section: Methodsmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

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Antinociceptive, anti‐inflammatory, and central nervous system (CNS) effects of the natural coumarin soulattrolide

Alonso-Castro

Guzmán-Gutiérrez

Betancourt

et al. 2018

Drug Development Research

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“…These compounds have also been shown to be active against clinical isolates of Mycobacterium tuberculosis. Moreover, in a toxicogenomic analysis in vivo performed by our group, we describe that these compounds were not toxic over non-tumoral tis-sues from CD-1 mice [12]. Interestingly, in 2004, Reyes-Chilpa et al [5] reported that mammea A/BA possess low cytotoxicity in vitro to normal human lymphocytes with an LC 100 of 126.45 mg/mL.…”

Section: Network Pharmacology Uncovers Anticancer Activity Of Mammea-mentioning

confidence: 81%

Network Pharmacology Uncovers Anticancer Activity of Mammea-Type Coumarins from Calophyllum brasiliense

et al. 2018

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Mammea-type coumarins are a particular type of secondary metabolites biosynthesized by the tropical rainforest tree , which is distributed from South America to Mexico. Particularly, mammea A/BA and A/BB (alone or as a mixture) possess biological properties such as cytotoxic and antitumoral activities, however, most of its molecular targets remain unknown. In this context, novel bioinformatic approaches, such as network pharmacology analysis, have been successfully used in herbal medicine to accelerate research in this field, and the support of experimental validations has been shown to be quite robust. In the present study, we performed a network pharmacology analysis to assess the possible molecular biological networks that interact with mammea A/BA and A/BB. Moreover, we validated the most relevant networks experimentally on K562 cancer cells. The results of the network pharmacology analysis indicate that mammea A/BA and A/BB interacts with cell death, PI3K/AKT, MAPK, Ras, and cancer pathways. The model shows that mammea A/BA and A/BB induce apoptosis through the overexpression of the proapoptotic proteins Bax and Bak, disrupt the autophagic flux as seen by the cytosolic accumulation of LC3-II and p62, disrupting the mitochondria ultrastructure and concomitantly increase the intracellular calcium concentration. Additionally, docking analysis predicted a possible interaction with a rapamycin-binding domain of mTOR. In conclusion, we validated network pharmacology analysis and report, for the first time, that mammea A/BA and A/BB coumarins induce apoptosis through the inhibition of the autophagic flux, possibly interacting with mTOR.

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“…Coumarins are good examples of this, since besides being ubiquitous in plant species, they present a wide range of pharmacological activities, as anti‐inflammatory, antioxidant, antiproliferative, and antimicrobial. In addition, they can be easily accessed by organic synthetic methodologies, which avoid issues inherent to obtaining bioactive molecules by exploitation of natural resources …”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo trypanocidal activities of 8‐methoxy‐3‐(4‐nitrobenzoyl)‐6‐propyl‐2H‐cromen‐2‐one, a new synthetic coumarin of low cytotoxicity against mammalian cells

et al. 2018

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Natural and synthetic coumarins have been described as prototypes of new drug candidates against Chagas' disease. During a typical screening with new compounds, we observed the potential of a new synthetic nitrobenzoylcoumarin (1) as trypanocidal against Trypanosoma cruzi epimastigotas. Then, we decided to prepare and evaluate a set of analogues from 1 to check the major structural requirements for trypanocidal activity. The structural variations were conducted in six different sites on the original compound and the best derivative (3) presented activity (IC 28 ± 3 μM) similar to that of benznidazole (IC 25 ± 10 μM). The enhancement of trypanocidal activity was conditioned to a change in the side chain at C6 (allyl to n-propyl group) and the preservation of coumarin nucleus and the nitrobenzoyl group at C3. Exposure of 3 to H9C2 cells showed low toxicity (CC > 200 μM) and its activity on T. cruzi amastigotes (IC 13 ± 0.3 μM) encouraged us to perform an evaluation of its potential when given orally to mice infected with trypomastigote forms. Derivative 3 was able to reduce parasitemia when compared to the group of untreated animals. Taken together, these results show the potential therapeutic application of the synthetic coumarins.

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Risk assessment of Soulatrolide and Mammea (A/BA+A/BB) coumarins from Calophyllum brasiliense by a toxicogenomic and toxicological approach

Cited by 10 publications

References 54 publications

Antinociceptive, anti‐inflammatory, and central nervous system (CNS) effects of the natural coumarin soulattrolide

Antinociceptive, anti‐inflammatory, and central nervous system (CNS) effects of the natural coumarin soulattrolide

Network Pharmacology Uncovers Anticancer Activity of Mammea-Type Coumarins from Calophyllum brasiliense

In vitro and in vivo trypanocidal activities of 8‐methoxy‐3‐(4‐nitrobenzoyl)‐6‐propyl‐2H‐cromen‐2‐one, a new synthetic coumarin of low cytotoxicity against mammalian cells

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