Oleanolic Acid Derivatives as Potential Inhibitors of HIV-1 Protease

Medina-O'Donnell, Marta; Rivas, Francisco; Reyes‐Zurita, Fernando J.; Cano-Muñoz, Mario; Martı́nez, Antonio; Lupiáñez, José A.; Parra, Andrés

doi:10.1021/acs.jnatprod.9b00649

Cited by 32 publications

(22 citation statements)

References 40 publications

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“…Since their structures are partially correlated, betulinic acid, oleanolic acid, ursolic acid, and some of their derivatives were identified as anti-HIV principles, even though ursolic acid is slightly toxic [59]. Moreover, ursolic acid and oleanolic acid have been reported to inhibit protease expression [60,61].…”

Section: Anti-hiv-1 Activity Of Pure Compounds Detected In Pgb Pgl and Pgpmentioning

confidence: 99%

In Vitro Anti-HIV-1 Reverse Transcriptase and Integrase Properties of Punica granatum L. Leaves, Bark, and Peel Extracts and Their Main Compounds

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In a search for natural compounds with anti-HIV-1 activity, we studied the effect of the ethanolic extract obtained from leaves, bark, and peels of Punica granatum L. for the inhibition of the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) and integrase (IN) LEDGF-dependent activities. The chemical analyses led to the detection of compounds belonging mainly to the phenolic and flavonoid chemical classes. Ellagic acid, flavones, and triterpenoid molecules were identified in leaves. The bark and peels were characterized by the presence of hydrolyzable tannins, such as punicalins and punicalagins, together with ellagic acid. Among the isolated compounds, the hydrolyzable tannins and ellagic acid showed a very high inhibition (IC50 values ranging from 0.12 to 1.4 µM and 0.065 to 0.09 µM of the RNase H and IN activities, respectively). Of the flavonoids, luteolin and apigenin were found to be able to inhibit RNase H and IN functions (IC50 values in the 3.7–22 μM range), whereas luteolin 7-O-glucoside showed selective activity for HIV-1 IN. In contrast, betulinic acid, ursolic acid, and oleanolic acid were selective for the HIV-1 RNase H activity. Our results strongly support the potential of non-edible P. granatum organs as a valuable source of anti-HIV-1 compounds.

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Section: Anti-hiv-1 Activity Of Pure Compounds Detected In Pgb Pgl and Pgpmentioning

confidence: 99%

In Vitro Anti-HIV-1 Reverse Transcriptase and Integrase Properties of Punica granatum L. Leaves, Bark, and Peel Extracts and Their Main Compounds

Sanna

Marengo

Acquadro

et al. 2021

Plants

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“…PTs have been screened for biological activities, and most of them displayed promising in vitro and in vivo potency [ 4 ]. A number of PTs and their derivatives are known to exhibit a wide range of biological activities such as anticancer [ 5 , 6 , 7 ], anti-HIV [ 8 , 9 , 10 ], anti-inflammatory [ 11 , 12 ], antimalarial [ 13 ], hepatoprotective [ 14 , 15 ], antimicrobial [ 16 , 17 ] antioxidant [ 18 , 19 ] and antidiabetic activities [ 20 ]. Currently, there is an increase in the number of patents being issued to protect new PTs with potential therapeutic effects, especially anticancer and antiviral [ 21 , 22 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Pentacyclic Triterpenoids with Nitrogen-Containing Heterocyclic Moiety, Privileged Hybrids in Anticancer Drug Discovery

et al. 2021

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Pentacyclic triterpenoids are well-known phytochemicals with various biological activities commonly found in plants as secondary metabolites. The wide range of biological activities exhibited by triterpenoids has made them the most valuable sources of pharmacological agents. A number of novel triterpenoid derivatives with many skeletal modifications have been developed. The most important modifications are the formation of analogues or derivatives with nitrogen-containing heterocyclic scaffolds. The derivatives with nitrogen-containing heterocyclic compounds are among the most promising candidate for the development of novel therapeutic drugs. About 75% of FDA-approved drugs are nitrogen-containing heterocyclic moieties. The unique properties of heterocyclic compounds have encouraged many researchers to develop new triterpenoid analogous with pharmacological activities. In this review, we discuss recent advances of nitrogen-containing heterocyclic triterpenoids as potential therapeutic agents. This comprehensive review will assist medicinal chemists to understand new strategies that can result in the development of compounds with potential therapeutic efficacy.

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“… 17 − 19 In addition, these triterpenoid conjugates have also been assayed as antiviral agents against HIV-1 protease, and some show submicromolar values and an activity gain of 100 times greater than that of their natural precursors. 20 …”

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confidence: 99%

Synthesis and Biological Activity of Triterpene–Coumarin Conjugates

et al. 2021

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A set of 12 maslinic acid–coumarin conjugates was synthesized, with 9 being maslinic acid–diamine–coumarin conjugates at the C-28 carboxylic acid group of triterpene acid and the other three being maslinic acid–coumarin conjugates at C-2/C-3 and/or C-28 of the triterpene skeleton. The cytotoxic effects of these 12 triterpene conjugates were evaluated in three cancer cell lines (B16-F10, HT29, and Hep G2) and compared, respectively, with three nontumor cell lines from the same or similar tissue (HPF, IEC-18, and WRL68). The most potent cytotoxic results were achieved by a conjugate with two molecules of coumarin-3-carboxylic acid coupled through the C-2 and C-3 hydroxy groups of maslinic acid. This conjugate showed submicromolar IC 50 values in two of the three cancer cell lines tested (0.6, 1.1, and 0.9 μM), being between 110- and 30-fold more effective than its corresponding precursor. Furthermore, this conjugate ( 10 ) showed percentages of cell viability for the three nontumor lines of 90%. Four maslinic acid–coumarin conjugates displayed apoptotic effects in the treated cells, with total apoptosis rates of between 40 and 85%, relative to the control. Almost all the compounds assayed caused cell-cycle arrest in all cancer cell lines, increasing the number of these cells in the G0/G1 phase.

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Oleanolic Acid Derivatives as Potential Inhibitors of HIV-1 Protease

Cited by 32 publications

References 40 publications

In Vitro Anti-HIV-1 Reverse Transcriptase and Integrase Properties of Punica granatum L. Leaves, Bark, and Peel Extracts and Their Main Compounds

In Vitro Anti-HIV-1 Reverse Transcriptase and Integrase Properties of Punica granatum L. Leaves, Bark, and Peel Extracts and Their Main Compounds

Pentacyclic Triterpenoids with Nitrogen-Containing Heterocyclic Moiety, Privileged Hybrids in Anticancer Drug Discovery

Synthesis and Biological Activity of Triterpene–Coumarin Conjugates

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