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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.


Key HMBC correlations for compound C
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Fig2: Key HMBC correlations for compound C

Mentions: Compound C was obtained as brownish needles from n-hexane-EtOAc, mp 155–157 °C. It reacted negatively to the FeCl3, suggesting the absence of a phenolic group in the molecule. Its molecular formula of C4H6N2O2, corresponding to 3 degrees of unsaturation, was determined by EI-MS (M+m/z 114) in conjunction with the NMR spectra. In the 13C NMR spectrum, signals at δC 173.8 (C-4) and 159.9 (C-2) for two carbonyl groups, one methylene signal at δC 29.2 (C-5) and one methyl at δC 53.9 (N-CH3), were characteristic of 1-methylhydantoin structure [7]. In the 1H NMR spectrum, two singlets were observed at δH 3.95 and 2.90, respectively, assignable to these methyl and methylene groups, respectively (Table 1). In the HMBC spectrum, pertinent correlations were observed between H-5 and C-2, CH3 and C-2 and C-4. The structure of compound C was established as 1-methyldiazolidine-2,4-dione (Fig. 2). It is a natural product from the Polygonum genus and has been fully characterized here for the first time. It has been previously reported as a synthetic compound and was found to be a renal metabolite of dupracetam [7].Table 1


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)

Key HMBC correlations for compound C
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: Key HMBC correlations for compound C
Mentions: Compound C was obtained as brownish needles from n-hexane-EtOAc, mp 155–157 °C. It reacted negatively to the FeCl3, suggesting the absence of a phenolic group in the molecule. Its molecular formula of C4H6N2O2, corresponding to 3 degrees of unsaturation, was determined by EI-MS (M+m/z 114) in conjunction with the NMR spectra. In the 13C NMR spectrum, signals at δC 173.8 (C-4) and 159.9 (C-2) for two carbonyl groups, one methylene signal at δC 29.2 (C-5) and one methyl at δC 53.9 (N-CH3), were characteristic of 1-methylhydantoin structure [7]. In the 1H NMR spectrum, two singlets were observed at δH 3.95 and 2.90, respectively, assignable to these methyl and methylene groups, respectively (Table 1). In the HMBC spectrum, pertinent correlations were observed between H-5 and C-2, CH3 and C-2 and C-4. The structure of compound C was established as 1-methyldiazolidine-2,4-dione (Fig. 2). It is a natural product from the Polygonum genus and has been fully characterized here for the first time. It has been previously reported as a synthetic compound and was found to be a renal metabolite of dupracetam [7].Table 1

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.