Naphthoquinones isolated from Diospyros anisandra exhibit potent activity against pan-resistant first-line drugs Mycobacterium tuberculosis strains

Andrés Humberto Uc-Cachón, Rocío Borges-Argáez, Salvador Said-Fernández, Javier Vargas-Villarreal, Francisco González-Salazar, Martha Méndez-González, Mirbella Cáceres-Farfán, Gloria María Molina-Salinas

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background and objectives: The recent emergence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) Mycobacterium tuberculosis (MTB) strains have further complicated the control of tuberculosis (TB). There is an urgent need of new molecules candidates to be developed as novel, active, and less toxic anti-tuberculosis (anti-TB) drugs. Medicinal plants have been an excellent source of leads for the development of drugs, particularly as anti-infective agents. In previous studies, the non-polar extract of Diospyros anisandra showed potent anti-TB activity, and three monomeric and five dimeric naphthoquinones have been obtained. In this study, we performed bioguided chemical fractionation and the isolation of eight naphthoquinones from D. anisandra and their evaluation of anti-TB and cytotoxic activities against mammalian cells. Methods: The n-hexane crude extract from the stem bark of the plant was obtained by maceration and liquid-liquid fractionation. The isolation of naphthoquinones was carried out by chromatographic methods and identified by gas chromatography and mass spectroscopy data analysis. Anti-TB activity was evaluated against two strains of MTB (H37Rv) susceptible to all five first-line anti-TB drugs and a clinical isolate that is resistant to these medications (pan-resistant, CIBIN 99) by measuring the minimal inhibitory concentration (MIC). Cytotoxicity of naphthoquinones was estimated against two mammalian cells, Vero line and primary cultures of human peripheral blood mononuclear (PBMC) cells, and their selectivity index (SI) was determined. Results: Plumbagin and its dimers maritinone and 3,3'-biplumbagin showed the strongest activity against both MTB strains (MIC = 1.56-3.33 μg/mL). The bioactivity of maritinone and 3,3'-biplumbagin were 32 times more potent than rifampicin against the pan-resistant strain, and both dimers showed to be non-toxic against PBMC and Vero cells. The SI of maritinone and 3,3'-biplumbagin on Vero cells was 74.34 and 194.11 against sensitive and pan-resistant MTB strains, respectively. Conclusion: Maritinone and 3,3'-biplumbagin possess a very interesting potential for development as new drugs against M. tuberculosis, mainly resistant profile strains. © 2013 Elsevier Ltd.
Original languageEnglish
Pages (from-to)114-120
Number of pages7
JournalPulmonary Pharmacology and Therapeutics
DOIs
Publication statusPublished - 1 Feb 2014
Externally publishedYes

Fingerprint

Diospyros
Naphthoquinones
Mycobacterium tuberculosis
Tuberculosis
Pharmaceutical Preparations
Vero Cells
Fractionation
Dimers
Blood Cells
Chemical Fractionation
Blood
Plant Bark
Cells
Plant Stems
Multidrug-Resistant Tuberculosis
Poisons
Liquids
Rifampin
Cytotoxicity
Medicinal Plants

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Biochemistry, medical
  • Pharmacology (medical)

Cite this

Uc-Cachón, Andrés Humberto ; Borges-Argáez, Rocío ; Said-Fernández, Salvador ; Vargas-Villarreal, Javier ; González-Salazar, Francisco ; Méndez-González, Martha ; Cáceres-Farfán, Mirbella ; Molina-Salinas, Gloria María. / Naphthoquinones isolated from Diospyros anisandra exhibit potent activity against pan-resistant first-line drugs Mycobacterium tuberculosis strains. In: Pulmonary Pharmacology and Therapeutics. 2014 ; pp. 114-120.
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abstract = "Background and objectives: The recent emergence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) Mycobacterium tuberculosis (MTB) strains have further complicated the control of tuberculosis (TB). There is an urgent need of new molecules candidates to be developed as novel, active, and less toxic anti-tuberculosis (anti-TB) drugs. Medicinal plants have been an excellent source of leads for the development of drugs, particularly as anti-infective agents. In previous studies, the non-polar extract of Diospyros anisandra showed potent anti-TB activity, and three monomeric and five dimeric naphthoquinones have been obtained. In this study, we performed bioguided chemical fractionation and the isolation of eight naphthoquinones from D. anisandra and their evaluation of anti-TB and cytotoxic activities against mammalian cells. Methods: The n-hexane crude extract from the stem bark of the plant was obtained by maceration and liquid-liquid fractionation. The isolation of naphthoquinones was carried out by chromatographic methods and identified by gas chromatography and mass spectroscopy data analysis. Anti-TB activity was evaluated against two strains of MTB (H37Rv) susceptible to all five first-line anti-TB drugs and a clinical isolate that is resistant to these medications (pan-resistant, CIBIN 99) by measuring the minimal inhibitory concentration (MIC). Cytotoxicity of naphthoquinones was estimated against two mammalian cells, Vero line and primary cultures of human peripheral blood mononuclear (PBMC) cells, and their selectivity index (SI) was determined. Results: Plumbagin and its dimers maritinone and 3,3'-biplumbagin showed the strongest activity against both MTB strains (MIC = 1.56-3.33 μg/mL). The bioactivity of maritinone and 3,3'-biplumbagin were 32 times more potent than rifampicin against the pan-resistant strain, and both dimers showed to be non-toxic against PBMC and Vero cells. The SI of maritinone and 3,3'-biplumbagin on Vero cells was 74.34 and 194.11 against sensitive and pan-resistant MTB strains, respectively. Conclusion: Maritinone and 3,3'-biplumbagin possess a very interesting potential for development as new drugs against M. tuberculosis, mainly resistant profile strains. {\circledC} 2013 Elsevier Ltd.",
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Naphthoquinones isolated from Diospyros anisandra exhibit potent activity against pan-resistant first-line drugs Mycobacterium tuberculosis strains. / Uc-Cachón, Andrés Humberto; Borges-Argáez, Rocío; Said-Fernández, Salvador; Vargas-Villarreal, Javier; González-Salazar, Francisco; Méndez-González, Martha; Cáceres-Farfán, Mirbella; Molina-Salinas, Gloria María.

In: Pulmonary Pharmacology and Therapeutics, 01.02.2014, p. 114-120.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Naphthoquinones isolated from Diospyros anisandra exhibit potent activity against pan-resistant first-line drugs Mycobacterium tuberculosis strains

AU - Uc-Cachón, Andrés Humberto

AU - Borges-Argáez, Rocío

AU - Said-Fernández, Salvador

AU - Vargas-Villarreal, Javier

AU - González-Salazar, Francisco

AU - Méndez-González, Martha

AU - Cáceres-Farfán, Mirbella

AU - Molina-Salinas, Gloria María

PY - 2014/2/1

Y1 - 2014/2/1

N2 - Background and objectives: The recent emergence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) Mycobacterium tuberculosis (MTB) strains have further complicated the control of tuberculosis (TB). There is an urgent need of new molecules candidates to be developed as novel, active, and less toxic anti-tuberculosis (anti-TB) drugs. Medicinal plants have been an excellent source of leads for the development of drugs, particularly as anti-infective agents. In previous studies, the non-polar extract of Diospyros anisandra showed potent anti-TB activity, and three monomeric and five dimeric naphthoquinones have been obtained. In this study, we performed bioguided chemical fractionation and the isolation of eight naphthoquinones from D. anisandra and their evaluation of anti-TB and cytotoxic activities against mammalian cells. Methods: The n-hexane crude extract from the stem bark of the plant was obtained by maceration and liquid-liquid fractionation. The isolation of naphthoquinones was carried out by chromatographic methods and identified by gas chromatography and mass spectroscopy data analysis. Anti-TB activity was evaluated against two strains of MTB (H37Rv) susceptible to all five first-line anti-TB drugs and a clinical isolate that is resistant to these medications (pan-resistant, CIBIN 99) by measuring the minimal inhibitory concentration (MIC). Cytotoxicity of naphthoquinones was estimated against two mammalian cells, Vero line and primary cultures of human peripheral blood mononuclear (PBMC) cells, and their selectivity index (SI) was determined. Results: Plumbagin and its dimers maritinone and 3,3'-biplumbagin showed the strongest activity against both MTB strains (MIC = 1.56-3.33 μg/mL). The bioactivity of maritinone and 3,3'-biplumbagin were 32 times more potent than rifampicin against the pan-resistant strain, and both dimers showed to be non-toxic against PBMC and Vero cells. The SI of maritinone and 3,3'-biplumbagin on Vero cells was 74.34 and 194.11 against sensitive and pan-resistant MTB strains, respectively. Conclusion: Maritinone and 3,3'-biplumbagin possess a very interesting potential for development as new drugs against M. tuberculosis, mainly resistant profile strains. © 2013 Elsevier Ltd.

AB - Background and objectives: The recent emergence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) Mycobacterium tuberculosis (MTB) strains have further complicated the control of tuberculosis (TB). There is an urgent need of new molecules candidates to be developed as novel, active, and less toxic anti-tuberculosis (anti-TB) drugs. Medicinal plants have been an excellent source of leads for the development of drugs, particularly as anti-infective agents. In previous studies, the non-polar extract of Diospyros anisandra showed potent anti-TB activity, and three monomeric and five dimeric naphthoquinones have been obtained. In this study, we performed bioguided chemical fractionation and the isolation of eight naphthoquinones from D. anisandra and their evaluation of anti-TB and cytotoxic activities against mammalian cells. Methods: The n-hexane crude extract from the stem bark of the plant was obtained by maceration and liquid-liquid fractionation. The isolation of naphthoquinones was carried out by chromatographic methods and identified by gas chromatography and mass spectroscopy data analysis. Anti-TB activity was evaluated against two strains of MTB (H37Rv) susceptible to all five first-line anti-TB drugs and a clinical isolate that is resistant to these medications (pan-resistant, CIBIN 99) by measuring the minimal inhibitory concentration (MIC). Cytotoxicity of naphthoquinones was estimated against two mammalian cells, Vero line and primary cultures of human peripheral blood mononuclear (PBMC) cells, and their selectivity index (SI) was determined. Results: Plumbagin and its dimers maritinone and 3,3'-biplumbagin showed the strongest activity against both MTB strains (MIC = 1.56-3.33 μg/mL). The bioactivity of maritinone and 3,3'-biplumbagin were 32 times more potent than rifampicin against the pan-resistant strain, and both dimers showed to be non-toxic against PBMC and Vero cells. The SI of maritinone and 3,3'-biplumbagin on Vero cells was 74.34 and 194.11 against sensitive and pan-resistant MTB strains, respectively. Conclusion: Maritinone and 3,3'-biplumbagin possess a very interesting potential for development as new drugs against M. tuberculosis, mainly resistant profile strains. © 2013 Elsevier Ltd.

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DO - 10.1016/j.pupt.2013.08.001

M3 - Article

SP - 114

EP - 120

JO - Pulmonary Pharmacology and Therapeutics

JF - Pulmonary Pharmacology and Therapeutics

SN - 1094-5539

ER -