Flavonoids as Potential Inhibitors of Retroviral Enzymes

Ko, Yeon-Ju; Oh, Hyun-Jeong; Ahn, Hyo-Min; Kang, Ho‐Jung; Kim, Jung-Hyun; Ko, Young Hwan

doi:10.3839/jksabc.2009.057

Cited by 21 publications

(13 citation statements)

References 23 publications

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“…The aim of our current work was to further explore the antiviral potential of protoflavonoids by preparing a series of less cytotoxic derivatives, and then test them against EBV and, while considering the antiretroviral activity of various other types of flavonoids [12][13][14], also against HIV. Many protoflavones are known for their potent anticancer activity and, until now, this is the bioactivity that is by far the most deeply investigated for this compound family.…”

Section: Introductionmentioning

confidence: 99%

Less Cytotoxic Protoflavones as Antiviral Agents: Protoapigenone 1′-O-isopropyl ether Shows Improved Selectivity Against the Epstein–Barr Virus Lytic Cycle

Vágvölgyi

Girst

Kúsz

et al. 2019

IJMS

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Protoflavones, a rare group of natural flavonoids with a non-aromatic B-ring, are best known for their antitumor properties. The protoflavone B-ring is a versatile moiety that might be explored for various pharmacological purposes, but the common cytotoxicity of these compounds is a limitation to such efforts. Protoapigenone was previously found to be active against the lytic cycle of Epstein–Barr virus (EBV). Further, the 5-hydroxyflavone moiety is a known pharmacophore against HIV-integrase. The aim of this work was to prepare a series of less cytotoxic protoflavone analogs and study their antiviral activity against HIV and EBV. Twenty-seven compounds, including 18 new derivatives, were prepared from apigenin through oxidative de-aromatization and subsequent continuous-flow hydrogenation, deuteration, and/or 4′-oxime formation. One compound was active against HIV at the micromolar range, and three compounds showed significant activity against the EBV lytic cycle at the medium-low nanomolar range. Among these derivatives, protoapigenone 1′-O-isopropyl ether (6) was identified as a promising lead that had a 73-times selectivity of antiviral over cytotoxic activity, which exceeds the selectivity of protoapigenone by 2.4-times. Our results open new opportunities for designing novel potent and safe anti-EBV agents that are based on the natural protoflavone moiety.

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Section: Introductionmentioning

confidence: 99%

Less Cytotoxic Protoflavones as Antiviral Agents: Protoapigenone 1′-O-isopropyl ether Shows Improved Selectivity Against the Epstein–Barr Virus Lytic Cycle

Vágvölgyi

Girst

Kúsz

et al. 2019

IJMS

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“…The main component of the 70% ethanol extract is apigenin flavonoid glycoside called Gendarusin A (Prajogo, 2014). Flavonoid compounds are known as an anti-HIV natural source of therapy for patients with AIDS by inhibiting HIV reverse transcriptase (Veljkovic et al, 2007;Ko et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

ANTIVIRAL ACTIVITY OF Justicia gendarussa Burm.f. LEAVES AGAINST HIV-INFECTED MT-4 CELLS

Widodo¹,

Widiyanti²,

Prajogo³

2018

AJID

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Backgrounds: Justicia gendarussa Burm.f. has been known to have anti-HIV activity. This study was conducted to evaluate the effect of incubation time on the antiviral activity of the J. gendarussa leaves extract on HIV-infected MT-4 cells in vitro. Molecular docking test was also conducted to determine the interaction of alkaloids and flavonoids on the J. gendarussa leaves against HIV-1 reverse transcriptase receptor. It is expected that this research will provide scientific information on the development of J. gendarussa leaves as an anti-HIV drug. Materials and Methods: In the activity test, the effect of incubation time on the antiviral activity of J. gendarussa leaves on HIV-infected MT-4 cells were evaluated. During the activity test, a parameter of cytolysis effect inhibition on MT-4 cell line was observed after 4 days and 6 days incubation period. The molecular docking test is performed by using Molegro Virtual Docker software to determine the interaction of alkaloid and flavonoid compounds of J. gendarussa leaves with HIV-1 reverse transcriptase receptor. Results: The incubation time influences the CC 50 and EC 50 value. Fractionated-70% ethanol extract of J. gendarussa leaves showed a higher anti-HIV activity with EC 50 = 3.045 x 10-9 μg/mL, SI = 6.309 x 10 12 (4 days of incubation) and EC 50 = 6.066 μg/mL, SI = 58494.845 (6 days of incubation). From molecular docking test, it was found that flavonoid of J. gendarussa leaves could inhibit the activity of HIV reverse transcriptase enzyme. Conclusion: Fractionated-70% ethanol extract of J. gendarussa has potential as an anti-HIV.

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“…The main component in the 70% ethanol extract is apigenin flavonoid glycoside called Gendarusin A (Prajogo et al, 2009). Flavonoid compounds act as a natural source of anti-HIV therapy for patients with AIDS by inhibiting HIV's reverse transcriptase (Veljkovic et al, 2007;Ko et al, 2009). Flavonoid compounds in high concentrations can be cytotoxic which causes an increase in the mitochondrial permeability, release of cytochrome c, activation of caspase, increased levels of p53 and p21, bcl-2 pressing, apoptosis induction, and the death of necrosis cell (Bolton et al, 2000;Inayat-Hussain et al, 2001: Morin et al, 2001Salvi et al, 2002;Shen et al, 2004;Lee et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

EFFECT OF VARYING INCUBATION PERIODS ON CYTOTOXICITY AND VIRUCIDAL ACTIVITIES OF Justicia gendarussa Burm.f. LEAF EXTRACT ON HIV-INFECTED MOLT-4 CELLS

Widiyanti¹,

Prajogo²,

Widodo³

2018

AJID

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Backgrounds: Justicia gendarussa Burm.f. has an anti-HIV activity. This study was conducted to evaluate the effects of incubation periods on the cytotoxicity and virucidal activities of the J. gendarussa leaves extract on MOLT-4 cells. Materials and Methods: The cytotoxicity assay was evaluated by using the WST-1 test with incubation periods of 3 days and 5 days. The virucidal activity test was determined by measuring the inhibitory activities on the syncytium formation. Results: The cytotoxicity assay showed the value of CC 50 on MOLT-4 cell culture with the test material of 70% ethanol extract of J. gendarussa leaves as much as 3928.620 µg /mL and 3176.581 µg /mL (incubation day 3 and day 5, respectively); fractionated-70% ethanol extract = 81782.428 µg /mL and 12175.870 µg/mL; and water extract = 16372.689 µg/mL and 2946.117 µg/mL. The test results of the virucidal activities (inhibit ≥ 90% the formation of syncytium) of 70% ethanol extract of J. gendarussa leaves is at a concentration 250 µg/mL, 500 µg/mL and 1000 µg/mL (3-day incubation) and 250 µg/mL (5-day incubation); and fractionated-70% ethanol extract at a concentration 250 µg /mL, 500 µg/mL and 1000 µg/mL (3-day incubation) and 1000 µg/mL (5-day incubation). Conclusion: 70% ethanol extract, fractionated-70% ethanol extract, and water extract of J. gendarussa leaves were relatively nontoxic toward MOLT-4 cells, and fractionated-70% ethanol extract had better potentials in virucidal activities.

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Flavonoids as Potential Inhibitors of Retroviral Enzymes

Cited by 21 publications

References 23 publications

Less Cytotoxic Protoflavones as Antiviral Agents: Protoapigenone 1′-O-isopropyl ether Shows Improved Selectivity Against the Epstein–Barr Virus Lytic Cycle

Less Cytotoxic Protoflavones as Antiviral Agents: Protoapigenone 1′-O-isopropyl ether Shows Improved Selectivity Against the Epstein–Barr Virus Lytic Cycle

ANTIVIRAL ACTIVITY OF Justicia gendarussa Burm.f. LEAVES AGAINST HIV-INFECTED MT-4 CELLS

EFFECT OF VARYING INCUBATION PERIODS ON CYTOTOXICITY AND VIRUCIDAL ACTIVITIES OF Justicia gendarussa Burm.f. LEAF EXTRACT ON HIV-INFECTED MOLT-4 CELLS

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