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Anti-leukemia activity of semi-synthetic phenolic derivatives from Polygonum limbatum Meisn.

Nkuété AH, Kuete V, Gozzini D, Migliolo L, Oliveira AL, Wabo HK, Tane P, Vidari G, Efferth T, Franco OL - Chem Cent J (2015)

Bottom Line: We describe in the present paper four new semi-synthetic derivatives of A and B: 5-hydroxy-6-methoxy-7-O-(3'-methylbut-2'-enyl)chroman-4-one (1), trivially named metapchromone, 5-acetoxy-6-methoxy-7-O-[3'-methylbut-2'enyl]chroman-4-one (2), trivially named sargisin, 2'-hydroxy-3',6'-dimethoxy-4'-O-(3″-methylbut-2″-enyl)chalcone (3) trivially named limbachalcone A, and 2'-acetoxy-3',6'-dimethoxy-4'-O-(3″-methylbut-2″-enyl)chalcone (4) trivially named tsedengchalcone.The study clearly suggests that semi-synthesis involving O-prenylation and acetylation of chalcones or other chromanones should be avoided in a search for anticancer drugs.This conclusion should be helpful when selecting substituents for the synthesis of potential anticancer drugs.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Faculty of Science, University of Dschang, Dschang, Cameroon ; Centro de Analises Proteômicas e Bioquimicas, Pós-Graduação em Ciencias Genomicas e Biotecnologia, Universidade Catolica de Brasilia, Brasilia, DF Brazil ; Dipartimento di Chimica, Laboratorio di Chimica delle Sostanze Organiche Naturali e Centro di Etnobiofarmacia (CISTRE), Università degli Studi di Pavia, Via Taramelli, 12-27100 Pavia, Italy.

ABSTRACT

Background: The present report describes the semi-synthesis of a few O-prenylated phenolic derivatives and their in vitro antitumor activities. These compounds were prepared by modifying two naturally occurring antitumor phenols, 5,7-dihydroxy-3-(1'-hydroxy-1'-phenyl-methyl)-6-methoxy-chroman-4-one (A) and 2',4'-dihydroxy-3',6'-dimethoxychalcone (B), previously isolated from Polygonum limbatum Meisn. (Polygonaceae). The structures were elucidated by spectroscopic means and comparison with published data. The cytotoxicity of compounds was determined by using the resazurin assay in the parental drug-sensitive CCRF-CEM cell line and its multidrug-resistant P-glycoprotein-over-expressing subline, CEM/ADR5000.

Results: We describe in the present paper four new semi-synthetic derivatives of A and B: 5-hydroxy-6-methoxy-7-O-(3'-methylbut-2'-enyl)chroman-4-one (1), trivially named metapchromone, 5-acetoxy-6-methoxy-7-O-[3'-methylbut-2'enyl]chroman-4-one (2), trivially named sargisin, 2'-hydroxy-3',6'-dimethoxy-4'-O-(3″-methylbut-2″-enyl)chalcone (3) trivially named limbachalcone A, and 2'-acetoxy-3',6'-dimethoxy-4'-O-(3″-methylbut-2″-enyl)chalcone (4) trivially named tsedengchalcone. Their preliminary cytotoxic activities have been determined. We also report herein the isolation of 1-methylhydantoin (C) and betulinic acid (D) from Polygonum limbatum for the first time.

Conclusions: The study clearly suggests that semi-synthesis involving O-prenylation and acetylation of chalcones or other chromanones should be avoided in a search for anticancer drugs. This conclusion should be helpful when selecting substituents for the synthesis of potential anticancer drugs.

No MeSH data available.


Semi-synthesis of compound 3 from 2′,4′-dihydroxy-3′,6′-dimethoxychalcone (B)
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Fig6: Semi-synthesis of compound 3 from 2′,4′-dihydroxy-3′,6′-dimethoxychalcone (B)

Mentions: Compound B (10 mg, 30 × 10−3 mmol) was dissolved in 3 mL of acetone (0.1 M); prenyl bromide (2 mL) and K2CO3 (3 mg) were added successively. The mixture was heated at 40 °C for 3 h (Fig. 6). Distilled H2O (10 mL) was then added to the mixture, which was stirred for 40 min. Extraction with CH2Cl2 (3 × 10 mL),dryingover Na2SO4, and chromatographic purification on a silica gel column with mixtures of n-hexane-EtOAc yielded, after crystallization, 2′-hydroxy-3′,6′-dimethoxy-4′-O-(3″-methylbut-2″-enyl)chalcone (3) (8.4 mg, 84 %), trivially named limbachalcone A.Fig. 6


Anti-leukemia activity of semi-synthetic phenolic derivatives from Polygonum limbatum Meisn.

Nkuété AH, Kuete V, Gozzini D, Migliolo L, Oliveira AL, Wabo HK, Tane P, Vidari G, Efferth T, Franco OL - Chem Cent J (2015)

Semi-synthesis of compound 3 from 2′,4′-dihydroxy-3′,6′-dimethoxychalcone (B)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4493792&req=5

Fig6: Semi-synthesis of compound 3 from 2′,4′-dihydroxy-3′,6′-dimethoxychalcone (B)
Mentions: Compound B (10 mg, 30 × 10−3 mmol) was dissolved in 3 mL of acetone (0.1 M); prenyl bromide (2 mL) and K2CO3 (3 mg) were added successively. The mixture was heated at 40 °C for 3 h (Fig. 6). Distilled H2O (10 mL) was then added to the mixture, which was stirred for 40 min. Extraction with CH2Cl2 (3 × 10 mL),dryingover Na2SO4, and chromatographic purification on a silica gel column with mixtures of n-hexane-EtOAc yielded, after crystallization, 2′-hydroxy-3′,6′-dimethoxy-4′-O-(3″-methylbut-2″-enyl)chalcone (3) (8.4 mg, 84 %), trivially named limbachalcone A.Fig. 6

Bottom Line: We describe in the present paper four new semi-synthetic derivatives of A and B: 5-hydroxy-6-methoxy-7-O-(3'-methylbut-2'-enyl)chroman-4-one (1), trivially named metapchromone, 5-acetoxy-6-methoxy-7-O-[3'-methylbut-2'enyl]chroman-4-one (2), trivially named sargisin, 2'-hydroxy-3',6'-dimethoxy-4'-O-(3″-methylbut-2″-enyl)chalcone (3) trivially named limbachalcone A, and 2'-acetoxy-3',6'-dimethoxy-4'-O-(3″-methylbut-2″-enyl)chalcone (4) trivially named tsedengchalcone.The study clearly suggests that semi-synthesis involving O-prenylation and acetylation of chalcones or other chromanones should be avoided in a search for anticancer drugs.This conclusion should be helpful when selecting substituents for the synthesis of potential anticancer drugs.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Faculty of Science, University of Dschang, Dschang, Cameroon ; Centro de Analises Proteômicas e Bioquimicas, Pós-Graduação em Ciencias Genomicas e Biotecnologia, Universidade Catolica de Brasilia, Brasilia, DF Brazil ; Dipartimento di Chimica, Laboratorio di Chimica delle Sostanze Organiche Naturali e Centro di Etnobiofarmacia (CISTRE), Università degli Studi di Pavia, Via Taramelli, 12-27100 Pavia, Italy.

ABSTRACT

Background: The present report describes the semi-synthesis of a few O-prenylated phenolic derivatives and their in vitro antitumor activities. These compounds were prepared by modifying two naturally occurring antitumor phenols, 5,7-dihydroxy-3-(1'-hydroxy-1'-phenyl-methyl)-6-methoxy-chroman-4-one (A) and 2',4'-dihydroxy-3',6'-dimethoxychalcone (B), previously isolated from Polygonum limbatum Meisn. (Polygonaceae). The structures were elucidated by spectroscopic means and comparison with published data. The cytotoxicity of compounds was determined by using the resazurin assay in the parental drug-sensitive CCRF-CEM cell line and its multidrug-resistant P-glycoprotein-over-expressing subline, CEM/ADR5000.

Results: We describe in the present paper four new semi-synthetic derivatives of A and B: 5-hydroxy-6-methoxy-7-O-(3'-methylbut-2'-enyl)chroman-4-one (1), trivially named metapchromone, 5-acetoxy-6-methoxy-7-O-[3'-methylbut-2'enyl]chroman-4-one (2), trivially named sargisin, 2'-hydroxy-3',6'-dimethoxy-4'-O-(3″-methylbut-2″-enyl)chalcone (3) trivially named limbachalcone A, and 2'-acetoxy-3',6'-dimethoxy-4'-O-(3″-methylbut-2″-enyl)chalcone (4) trivially named tsedengchalcone. Their preliminary cytotoxic activities have been determined. We also report herein the isolation of 1-methylhydantoin (C) and betulinic acid (D) from Polygonum limbatum for the first time.

Conclusions: The study clearly suggests that semi-synthesis involving O-prenylation and acetylation of chalcones or other chromanones should be avoided in a search for anticancer drugs. This conclusion should be helpful when selecting substituents for the synthesis of potential anticancer drugs.

No MeSH data available.