Synthesis and anticancer activity of 3′-[4-fluoroaryl-(1,2,3-triazol-1-yl)]-3′-deoxythymidine analogs and their phosphoramidates

Abstract

A series of novel 4-chlorophenyl N-alkyl phosphoramidates of 3′-[4-fluoroaryl-(1,2,3-triazol-1-yl)]-3′-deoxythymidines (20–49) was synthesized by means of phosphorylation of 3′-[4-aryl-(1,2,3-triazol-1-yl)]-3′-deoxythymidines (7–11) with 4-chlorophenyl phosphoroditriazolide (14), followed by a reaction with the appropriate amine. The synthesized compounds 7–11 and 20–49 were evaluated along with four known anticancer compounds for their cytotoxic activity in human cancer cell lines: cervical (HeLa), nasopharyngeal (KB), breast (MCF-7), osteosarcoma (143B) (only selected compounds 20, 24, 28, 32–36, 38, 40, 46) and normal human dermal fibroblast cell line (HDF) using the sulforhodamine B (SRB) assay. Among 3′-[4-aryl-(1,2,3-triazol-1-yl)]-3′-deoxythymidines (7–11) the highest activity in all the investigated cancer cells was displayed by 3′-[4-(3-fluorophenyl)-(1,2,3-triazol-1-yl)]-3′-deoxythymidine (9) (IC₅₀ in the range of 2.58–3.61?μM) and its activity was higher than that of cytarabine. Among phosphoramidates 20–49 the highest activity was demonstrated by N-n-propyl phosphoramidate of 3′-[4-(3-fluorophenyl)-(1,2,3-triazol-1-yl)]-3′-deoxythymidine (35) in all the cancer cells (IC₅₀ in the range of 0.97–1.94?μM). Also N-ethyl phosphoramidate of 3′-[4-(3-fluorophenyl)-(1,2,3-triazol-1-yl)]-3′-deoxythymidine (33) exhibited good activity in all the used cell lines (IC₅₀ in the range of 4.79–4.96?μM).     

ACYCLIC NUCLEOSIDE/NUCLEOTIDE ANALOGUES WITH AN IMIDAZOLE RING SKELETON

Syntheses of a few acyclic nucleoside and acyclic nucleoside phosphonate analogues containing an imidazole ring have been reported. These analogues include methyl 1-(2-hydroxyethoxymethyl)imidazole-4,5-dicarbo-xylate (1), 4,5-dicarbamoyl-1-(2-hydroxyethoxymethyl)imidazole (2), 4,5-dicya-no-1-(2-hydroxyethoxymethyl)imidazole (4), Methyl 1-(2-bromoethoxymethyl)- imidazole-4,5-dicarboxylate (7), 4,5-dicyano-(2-bromoethoxymethyl)imidazole (8), and Methyl 1-(2-phosphonomethoxyethyl)imidazole (10). Also reported are a few potential prodrugs of the above compounds, including the acetyl derivatives 5 and 6 (of 1 and 4, respectively), and the diethyl phosphonate ester 9 (of 10). In addition, the corresponding benzyl-protected precursors 11 and 12 (of 1 and 4, respectively), along with their common hydrolysis product, 1-(2-benzyloxy-ethoxymethyl)-4,5-imidazoledicarboxylic acid (3), are reported. Another potential prodrug included in the list is 1-(2-acetoxyethyl)-4,5-dicyanoimidazole (15). The compounds were screened for in vitro antiviral activity against a wide variety of herpes and respiratory viruses. The most active compound was the phosphonate analogue 9 which exhibited an anti-measles virus activity with an EC₅₀ of <2.5 μg/mL and an SI value of > 176.     

Desferrithiocin analogue iron chelators: iron clearing efficiency,tissue distribution,and renal toxicity

The current solution to iron-mediated damage in transfusional iron overload disorders is decorporation of excess unmanaged metal, chelation therapy. The clinical development of the tridentate chelator deferitrin (1, Table 1) was halted due to nephrotoxicity. It was then shown by replacing the 4′-(HO) of 1 with a 3,6,9-trioxadecyloxy group, the nephrotoxicity could be ameliorated. Further structure–activity relationship studies have established that the length and the position of the polyether backbone controlled: (1) the ligand’s iron clearing efficiency (ICE), (2) chelator tissue distribution, (3) biliary ferrokinetics, and (4) tissue iron reduction. The current investigation compares the ICE and tissue distribution of a series of (S)-4,5-dihydro-2-[2-hydroxy-4-(polyether)phenyl]-4-methyl-4-thiazolecarboxylic acids (Table 1, 3–5) and the (S)-4,5-dihydro-2-[2-hydroxy-3-(polyether)phenyl]-4-methyl-4-thiazolecarboxylic acids (Table 1, 8–10). The three most effective polyether analogues, in terms of performance ratio (PR), defined as mean ICE_primate/ICE_rodent, are 3 (PR 1.1), 8, (PR 1.5), and 9, now in human trials, (PR 2.2). At the onset of the clinical trial on 9, no data were available for ligand 3 or 8. This is unfortunate, as 3 has many advantages over 9, e.g., the ICE of 3 in rats is 2.5-fold greater than that of 9 and analogue 3 achieves very high levels in the liver, pancreas, and heart, the organs most affected by iron overload. Finally, the impact of 3 on the urinary excretion of kidney injury molecule-1 (Kim-1), an early diagnostic biomarker for monitoring acute kidney toxicity, has been carried out in rats; no evidence of nephrotoxicity was found. Overall, the results suggest that 3 would be a far superior clinical candidate to 9.     

Pyrazole Related Nucleosides 5.1 Synthesis and Biological Activity of 2′-Deoxy- 2′, 3′-dideoxy- and Acyclo-analogues of 4-Iodo-1-β-D-ribofuranosyl-3-carboxymethyl Pyrazole (IPCAR)

Abstract

Continuing our studies on the structure-activity relationships (SAR) of 4-iodo-1-β-D-ribofuranosyl-3-carboxymethyl pyrazole (IPCAR), the ribofuranosyl moiety has been substituted with acyclic chains, namely 1-[(2-hydroxyethoxy)methyl]- and 1-[(1,3-dihydroxy-2-propoxy)methyl]-pyrazole derivatives (4, 5 and 8, 9 respectively), with the 2′-deoxy-β-D-ribofuranosyl group (12 and 13) and finally with the 2′,3′-dideoxy-D-glycero-pentofuranosyl-moiety (16 and 17). None of the new compounds display any interesting biological activity.     

Heat-Melt of β-1, 3-d-Glucan Gel

Six new products of oxidation of indolyl-3-acetic add catalyzed by horseradish peroxidase were isolated, along with four known ones, 3-hydroxymethyloxindole (1), 3-methyleneoxindole (2), indolyl-3-aldehyde (4), and 3,3-diindolylmethane (10). Based on spectroscopic and chemical evidence, the new products were identified as 3-acetoxyindole (3), 3-(indol-3-ylmethyl)oxindole (6), 3-[(2-mdol-3-ylmethyl)indol-3-ylmethyl]oxindole (9), the 3-hydroxymethyl compounds of 6 and 9 (5 and 7), and 2-(indol-3-ylmethyl)indolyl-3-acetic acid (8), respectively.     

Book Reviews

Unearthing Garden Mysteries: Experiments For Kids. Ellen Talmage. Golden, Colo.: Fulcrum Publishing. 2000. 90 pp. $17.95 (paperback). ISBN: 1-55591-993-6.

Greening School Grounds: Creating Habitats For Learning. Tim Grant and Gail Littlejohn (eds.). Gabriola Island, BC, Canada: New Society Publishers. 2001. 136 pp. $16.95 (paperback). ISBN: 0-86571-436-3.

Science Projects About Sound. Robert Gardner. Berkeley Heights, N.J.: Enslow. 2000. 112 pp. $19.95 (hardcover). ISBN: 0-7660-1166-6.

The Science of Sound and Music. Shar Levine and Leslie Johnstone. New York: Sterling Publishing. 2000. 80 pp. $19.95 (hardcover). ISBN: 0-8069-7183-5.

Elephants and Their Young. Great Explorations in Mathematics and Science (GEMS). Berkeley, Calif.: University of California, Lawrence Hall of Science. 2001. 100 pp. $18 (paperback). ISBN: 0-924886-55-2.

Mia2: Romaine's New Hat. Montreal, Quebec, Canada: Kotoka Kids Interactive. ($19.99 from Amazon.com).

System Requirements: PC. O/S: Windows 95 or better, CPU: Pentium 166MMX, RAM: 32 MB (64MB recommended), Video: 640 × 480 (256 colors), Sound: 16-bit Sound Blaster or 100% compatible, CD-ROM: 6X, 40 MB of hard drive disk space.

Macintosh: O/S: Systems 8.1 or better (System 9 requires 64 MB of Ram), CPU: PowerPC 275mhz, G3 233mhz, iMac, RAM: 32 MB (64 MB recommended), Video: 640 × 480 (256 colors), Sound: Standard Macintosh, CD-ROM: 6X, 40 MB of hard drive disk space.     

Highly selective biotransformation of (+)-(1S)- and (−)-(1R)-camphorquinone by Aspergillus wentii

Abstract

To clarify the structures of biotransformation products and metabolic pathways, the biotransformation of monoterpenoids, (+)- and (?)-camphorquinone (1a and b), has been investigated using Aspergillus wentii as a biocatalyst. Compound 1a was converted to (?)-(2S)-exo-hydroxycamphor (2a), (?)-(2S)-endo-hydroxycamphor (3a), (?)-(3S)-exo-hydroxycamphor (4a), (?)-(3S)-endo-hydroxycamphor (5a), and (+)-camphoric acid (6a). Compound 1b was converted to (+)-(2R)-exo-hydroxycamphor (2b), (+)-(2R)-endo-hydroxycamphor (3b), (+)-(3R)-exo-hydroxycamphor (4b), (+)-(3R)-endo-hydroxycamphor (5b), and (?)-camphoric acid (6b). Compound 1a mainly produced 2a (65.0%) with stereoselectivity, whereas 1b afforded 3b (84.3%) with high stereoselectivity. These structures were confirmed by gas chromatography–mass spectrometry, infrared, ¹H nuclear magnetic resonance (NMR), and ¹³C NMR spectral data. The products illustrate the marked ability of A. wentii for enzymatic oxidation and ketone reduction.     

Synthesis and Biological Evaluation of 2′,3′-Dideoxy-3′-Fluororibofuranosyl Purine Nucleosides

Abstract

Synthesis of 9-(2,3-dideoxy-3-fluoro-β-D-ribofuranosyl)-2-chloroadenine (7b) and -2-chloro-6-methoxypurine (9b), as well as the α-D-anomer 7a of the former and its N isomer 10a is reported. Among the compounds synthesized, only the β-D-anomer 7b displays moderate cytotoxic activity.     

Furanofuran lignans from Vitex negundo seeds

A new furanofuran lignan, vitelignin A (1), together with eight known lignan derivatives, were isolated from the seeds of Vitex negundo. Their structures were identified as (+)-4-oxo-8-hydroxy-2,6-di(3,4-methylenedioxy)phenyl-3,7-dioxabicyclo[3.3.0]octane (1), 4-oxosesamin (2), (+)-sesamin (3), (+)-paulownin (4), 4-hydroxysesamin (5), 4,8-dihydroxysesamin (6), 4-oxopaulownin (7), (+)-2-(3-methoxy-4-hydroxyphenyl)-6-(3,4-methylenedioxy)phenyl-3,7-dioxabicyclo[3.3.0]octane (8), and (+)-pinoresinol (9), respectively, based on extensive NMR and MS spectroscopic studies. Compounds 1, 2, and 7 showed moderate antifungal activity in vitro.     

Dinucleoside Polyphosphate NAD Analogs as Potential NMN Adenylyltransferase Inhibitors. Synthesis and Biological Evaluation

Abstract

Two dinucleoside polyphosphate NAD analogs, P¹-(adenosine-5′)-P³-(nicotinamide riboside-5′)triphosphate (Np₃A, 1) and P¹-(adenosine-5′)-P⁴-(nicotinamide riboside-5′)tetraphosphate (Np₄A, 2), were synthesized and tested as inhibitors of both microbial and human recombinant NMN adenylyltransferase. Compounds 1 and 2 proved to be selective inhibitors of microbial enzymes.     

SYNTHESIS AND BIOLOGICAL EVALUATION OF SOME ACYCLIC α-(1H-PYRAZOLO[3,4-d]PYRIMIDIN-4-YL)THIOALKYLAMIDE NUCLEOSIDES

ABSTRACT

The chemical synthesis of some acyclic α-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)thioalkylamide nucleosides (10–12)a–c is described. The treatment of 1H-pyrazolo[3,4-d]pyrimidin-4-thione 1 with compounds 2a–c gave, regioselectively, ethyl α-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)thioalkylates 3a-c, respectively. These heterocycles were alkylated, separately, with alkylating agents 4, 5 and 6 to give, regioselectively, the N₁-acyclic nucleosides (7-9)a-c which were deprotected to afford the desired products (10-12)a-c. All synthetic compounds were characterized on the basis of their physical and spectroscopic properties. The products (10-12)a–c were evaluated for their inhibitory effects against the replication of HIV-1 (III_B), HIV-2 (ROD), various DNA viruses, a variety of tumor-cell lines and M. tuberculosis. No marked biological activity was found.     

真菌Talaromyces stipitatus WH4-2中的抗菌活性成分

【目的】对真菌菌株WH4-2进行鉴定并分离鉴定具有抗菌活性的天然产物。【方法】综合菌落形态和ITS全序列分析,鉴定菌株种属。以抗菌活性分析为导向对其中的活性组分进行分离纯化,波谱分析鉴定结构。采用微量稀释法对化合物进行活性复筛,得最小抑菌浓度MIC值。【结果】真菌菌株WH4-2鉴定为Talaromyces stipitatus。从其土豆发酵液中分离鉴定化合物1 (5S-arugosin K)、2 (5R-arugosin K)、3 (5S-arugosin M)、4 (5R-arugosin M)和5 (Chrysophanol),其中1–4为含异戊烯基的dibenzo[b,e]oxepinone类化合物,5为蒽醌类化合物。1–4对Staphylococcus aureus ATCC43300、ATCC33591,Enterococcus faecium ATCC35667和Bacillussubtilis ATCC6633具有抗菌活性。【结论】含异戊烯基的Dibenzo[b,e]oxepinone类化合物是真菌T. stipitatus中抗菌活性成分。     

SYNTHESIS AND BIOLOGICAL EVALUATION OF SOME 4-SUBSTITUTED 1-[1-(4-HYDROXYBUTYL)-1,2,3-TRIAZOL-(4 & 5)-YLMETHYL]-1H-PYRAZOLO-[3,4-d]PYRIMIDINES

The synthesis of 1-[1-(4-hydroxybutyl)-1,2,3-triazol-(4 and 5)-ylmethyl] -1H-pyrazolo[3,4-d]pyrimidines 11a,b, 12a,b and 13–17 as carboacyclic nucleosides is described. The compounds 8a,b were condensed, separately, with compound 7 via 1,3-dipolar cycloaddition reaction to afford, after separation and deprotection, 1,4-regioisomers 11a,b and 1,5-regioisomers 12a,b. The deprotected carboacyclic nucleosides 11a served as precursor for the preparation of 4-amino 13, 4-methylamino 14, 4-benzylamino 15, 4-methoxy 16 and 4-hydroxy 17 analogues. All deprotected carboacyclic nucleosides were evaluated for their inhibitory effects against the replication of HIV-1(III_B), HIV-2(ROD), various DNA viruses, a variety of tumor-cell lines and tuberculosis. No marked biological activity was found.     

Synthesis of 1-Hydroxy-10-methyl-pyrimido [1, 6-C][1, 3]oxazine and the Oxazepine Derivative,Structural Mimicry of Anti-Constrained Acyclic Thymidine

Abstract

A number of pyrimido[1, 6-c][1, 3]oxazine and -oxazepine derivatives, mimicry analogs of anti-constrained acyclic thymidine, have been prepared via treatment of lithiated 5, 6-dimethyl-2, 4-dimethoxypyrimidine with benzylchloromethyl ether or oxiran to furnish 2, 4-dimethoxy-6-(1-benzyloxyethyl)-S-methylpyrimidine (2) and 2, 4-dimethoxy-6-(1-hydroxypropyl)-5-methylpyrimidine (8), respectively. Debenzylation of 2 afforded 2, 4-dimethoxy-6-(1-hydroxyethyl)-5-methylpyrimidine (3). Chloromethylation of 3 and 8 with paraformaldehyde and gaseous hydrogen chloride produced reactive chloromethyl ether intermediates which were converted to the cyclized products 9-methyl-(1H, 2H, 4H, 7H)-pyrimido[1, 6-c][1, 3]-oxazine (5) and -oxazepine (9)-6, 8-dione, respectively. By using selenium dioxide, allylic oxidation of 5 and 9 afforded the target compounds, a racemic mixture of (±)1-hydroxy-9-methyl-(1H, 2H, 4H, 7H)-pyrimido[1, 6-c][1, 3]-oxazine (6) and -oxazepine (10)-6, 8-dione, respectively. Compounds 5, 6, 7, 9, and 10 were evaluated for activity against human immunodeficiency virus (HIV), herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV). All of these compounds were inactive.     

The Pharmacological effects of novel 5-fluoro-N-(9,10-dihydro-9,10-dioxoanthracen-8-yl)-1H-indole-2-carboxamide derivatives on plasma lipid profile of Triton-WR-1339-induced Wistar rats

A novel series of 5-fluoro-N-(9,10-dihydro-9,10-dioxoanthracen-8-yl)-1H-indole-2-carboxamides (3c–3g) were synthesized. The present study was undertaken to investigate the possible antihyperlipidemic effect of these novel compounds on hyperlipidemic rats. Hyperlipidemia was induced by a single intraperitoneal injection of Triton WR-1339 (300 mg/kg). The tested animals were divided into normal control (NCG), hyperlipidemic control (HCG), compounds 3c-, 3d-, 3e-, 3f-, 3g- and bezafibrate (BF)-treated groups. At a dose of 15 mg/kg, compounds 3c–3g and BF (100 mg/kg) significantly (p < 0.0001) reduced elevated plasma triglycerides levels after 12 and 24 h compared to the hyperlipidemic control group. However, only compounds 3e and 3g obviously showed a significant (p < 0.0001) reduction in plasma total cholesterol levels after 12 and 24 h. Moreover, high-density lipoprotein cholesterol levels were significantly increased in all treated groups. The current study demonstrates that 5-fluoro-N-(9,10-dihydro-9,10-dioxoanthracen-8-yl)-1H-indole-2-carboxamides (3c–3g) have a definite antihyperlipidemic potential and these beneficial activities may contribute to their cardioprotective and antiatherosclerotic role.     

Preparation of Optically Pure cis-2,4-Dimethyl-l-cyclohexanones,the Key Intermediates in Cycloheximide Synthesis,Using Microbial Resolution

Asymmetric hydrolysis of acetate (10) of (±)-t-2,t-4-dimethyl-r-l-cyclohexanol with Bacillus subtilis var. niger gave (?)-(lS,2S,4S)-2,4-dimethyl-l-cyclohexanol (6a) and (+)-(1R,2R,4R)-acetate (10b) with high optical purities. Optically pure (?) and (+)-alcohols (6a and 6b) were prepared via corresponding 3,5-dinitrobenzoates. Oxidation of alcohols (6a and 6b) with chromic acid gave optically pure (?)-(2S,4S) and (+)-(2R,4R)-2,4-dimethyl-l-cyclohexanones (2a and 2b), respectively.     

Stereospecific Synthesis and Anti-HIV Activity of (Z)2′- and (E)3′-Deoxy-2′(3′)-C-(chloromethylene) Pyrimidine Nucleosides

Abstract

Reaction of 1-[2,5(and 3,5)-di-O-trityl-β-D-erythro-pentofuran-3 (and 2)-ulosyl]uracil derivatives 5 and 6 with (chloromethyl)triphenylphosphorane resulted in the stereoselective formation of (E)-3′- and (Z)-2′-chloromethylene derivatives 7 (69%) and 8 (53%), respectively, deprotection of which gave 9 and 10. Transformation of the uracil nucleoside 7 into cytosine one followed by deprotection yielded 12. The latter was converted into the arabinoside 14. The fully deprotected chloromethylene nucleosides were tested for their activity against HIV-1 and HIV-2.     

Antifouling activity of sponge-derived polybrominated diphenyl ethers and synthetic analogues

The antifouling (AF) activity of 2-hydroxy-4-(3-hydroxy-5-methylphenoxy)- 6-methylbenozoic acid methyl ester (1), 3,5-dibromo-2-(2′,4′-dibromophenoxy)phenol (2); 3,4,5-tribromo-2-(2′,4′-dibromophenoxy)phenol (3), 3,4,5-tribromo-2-(2′-bromophenoxy)phenol (4), 3,5-dibromo-2(2′,4′-dibromophenoxy)phenol (5), 3,4,5,6-tetrabromo-2-(2′-bromophenoxy)phenol (6); 4-phenoxyphenol (7), 4-phenoxyaniline (9), 1-chloro-4-phenoxybenzene (10); 1-bromo-4-phenoxybenzene (13) was investigated against marine bacteria, a diatom, barnacle larvae and mussel juveniles. The naturally occurring compound 2 showed the strongest AF activity in all bioassays but lacked toxicity. It inhibited the growth of all tested bacterial strains (MIC = 0.02 – 1.52 μM) and its 50% effective concentrations (EC₅₀) were 0.24 μM (diatom test), 0.66 μM (mussel test) and 1.26 μM (barnacle test). Among the commercially available derivates, compound 7 was the most active in bacterial and diatom bioassays but its activity was lower than that of compound 2. Overall, the naturally occurring compounds showed stronger activity than the commercially available analogues and could be possible future non-toxic AF candidates.     

Ring-Opening of 3-β-D-Ribofuranosyl-3,7,8,9-Tetrahydropyrimido [1,2-i]Purin-8-ol and Preparation of 2-Thio- and 2-aza-Adenosine Derivatives

The adduct 3-β-D-ribofuranosyl-3,7,8,9-tetrahydropyrimido[1,2-i]purin-8-ol (2), obtained from adenosine and epichlorohydrin, underwent ring fission at basic conditions. The initial ring-opening took place at C2 of the pyrimidine unit resulting in 2-(5-amino-1-β-D-ribofuranosyl-imidazol-4-yl)-1,4,5,6-tetrahydropyrimidin-5-ol (3). Also the tetrahydropyrimidine ring of 3 could be opened resulting in 5-amino-1-(β-D-ribofuranosyl)-imidazole-4-(N-3-amino-2-hydroxyl-propyl)-carboxamide (4). In hot acid conditions, 2 was both deglycosylated and ring-opened yielding 2-(5-amino-imidazol-4-yl)-1,4,5,6-tetrahydropyrimidin-5-ol (7) as the final product. When reacting 3 with CS₂ or HNO₂ ring-closure took place and 3-β-D-ribofuranosyl-3,4,7,8,9-pentahydropyrimido[1,2-i]purin-8-ol-5-thione (5), and 3-β-D-ribofuranosyl-imidazo[4,5-e]-3,7,8,9-tetrahydropyrimido[1,2-c][1,2,3]triazine-8-ol (6), respectively, were obtained. Also, the pyrimidine ring of the epichlorohydrin adduct with adenine, 10-imino-5,6-dihydro-4H,10H-pyrimido[1,2,3-cd]purin-5-ol (10), underwent ring fission and the product was identified as 3-hydroxy-1,2,3,4-tetrahydroimidazo[1,5-a]pyrimidine-8-carboximidamide (11).     

Two new anti-plasmodial flavonoid glycosides from Duranta repens

The CHCl₃-soluble fraction of the whole plant of Duranta repens showed anti-plasmodial activity against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum, with IC₅₀ values of 8.5?±?0.9 and 10.2?±?1.5?μg/mL, respectively. From this fraction, two new flavonoid glycosides, 7-O-α-d-glucopyranosyl-3,4′-dihydroxy-3′-(4-hydroxy-3-methylbutyl)-5,6-dimethoxyflavone (1) and 7-O-α-d-glucopyranosyl(6′′′-p-hydroxcinnamoyl)-3,4′-dihydroxy-3′-(4-hydroxy-3-methylbutyl)-5,6-dimethoxyflavone (2), along with five known flavonoids, 3,7,4′-trihydroxy-3′-(4-hydroxy-3-methylbutyl)-5,6-dimethoxyflavone (3), 3,7-dihydroxy-3′-(4-hydroxy-3-methylbutyl)-5,6,4′-trimethoxyflavone (4), 5,7-dihydroxy-3′-(2-hydroxy-3-methyl-3-butenyl)-3,6,4′-trimethoxyflavone (5), 3,7-dihydroxy-3′-(2-hydroxy-3-methyl-3-buten-yl)-5,6,4′-trimethoxyflavone (6), and 7-O-α-d-glucopyranosyl-3,5-dihydroxy-3′-(4′′-acetoxy-3′′-methylbutyl)-6,4′-dimethoxyflavone (7), have been isolated as anti-plasmodial principles. Their structures were deduced by spectroscopic analysis including 1D and 2D NMR techniques. The compounds (1–7) showed potent anti-plasmodial activities against D6 and W2 strains of Plasmodium falciparum, with IC₅₀ values in the range of 5.2–13.5?μM and 5.9–13.1?μM, respectively.