Antimycobacterial activity: a facile three-component [3+2]-cycloaddition for the regioselective synthesis of highly functionalised dispiropyrrolidines

A series of twelve dispiropyrrolidines were synthesized using [3+2]-cycloaddition reactions. The synthesized compounds were screened for their antimycobacterial activity against M. tuberculosis H(37)Rv and INH resistant M. tuberculosis strains using agar dilution method, four of them showed good activity with MIC of less than 1 μM. Compound 4'-[5-(4-fluorophenyl)pyridin-3-yl]-1'-methyldispiro[indan-2,2' pyrrolidine-3',2″-indan]-1,3,1″-trione (4b) was found to be the most active with MIC of 0.1215 and 5.121 μM, respectively.     

The synthesis of some branched-chain-sugar nucleoside analogues.

1-(2,3-Epoxy-5-O-trityl-beta-D-lyxofuranosyl)uracil was treated with a number of carbon nucleophiles. Ethynyl lithium gave 3'-deoxy-3'-ethynyl-5'-O-trityl-ara-uridine, which was reduced to the corresponding 3'-ethenyl compound. Sodium cyanide gave 3'-cyano-3'-deoxy-5'-O-trityl-ara-uridine which upon alkaline hydrolysis gave the corresponding 3'-carboxamido compound. 1,3-Dithian-2-yl lithium gave 3'-deoxy-3'-(1,3-dithian-2-yl)-5'-O-trityl-ara-uridine. The trityl group was removed from each of these compounds by mild acidic hydrolysis. Treatment of 2 with 0.1M H2sO4 and mercury (II) acetate afforded 3'-acetyl-3'-deoxy-ara-uridine which upon reduction with NaBH4 gave 3'-deoxy-3'-(1-hydroxyethan-1-yl)-ara-uridine. Acetylation of 6 yielded 5'-O-acetyl-3'-acetyl-2',3'-didehydro-2',3'-dideoxyuridine which upon reduction with NaBH4 produced a mixture of 5'-O-acetyl-2',3'-didehydro-2',3'-dideoxy-3'-(1-hydroxyethan -1-yl)uridine and 1-(R)[5-(S)-acetoxymethyl-4-(1-hydroxyethan-1-yl)-tetrahydrofuran- 2-yl]- uracil. Reduction of 14 with Raney nickel followed by removal of the trityl group gave 3'-deoxy-3'-methyl-ara-uridine.     

A Combined Patch-Clamp and Electrorotation Study of the Voltage- and Frequency-Dependent Membrane Capacitance Caused by Structurally Dissimilar Lipophilic Anions

Interactions of structurally dissimilar anionic compounds with the plasma membrane of HEK293 cells were analyzed by patch clamp and electrorotation. The combined approach provides complementary information on the lipophilicity, preferential affinity of the anions to the inner/outer membrane leaflet, adsorption depth and transmembrane mobility. The anionic species studied here included the well-known lipophilic anions dipicrylamine (DPA⁻), tetraphenylborate (TPB⁻) and [W₂(CO)₁₀(S₂CH)]⁻, the putative lipophilic anion and three new heterocyclic W(CO)₅ derivatives. All tested anions partitioned strongly into the cell membrane, as indicated by the capacitance increase in patch-clamped cells. The capacitance increment exhibited a bell-shaped dependence on membrane voltage. The midpoint potentials of the maximum capacitance increment were negative, indicating the exclusion of lipophilic anions from the outer membrane leaflet. The adsorption depth of the large organic anions DPA⁻, TPB⁻ and increased and that of W(CO)₅ derivatives decreased with increasing concentration of mobile charges. In agreement with the patch-clamp data, electrorotation of cells treated with DPA⁻ and W(CO)₅ derivatives revealed a large dispersion of membrane capacitance in the kilohertz to megahertz range due to the translocation of mobile charges. In contrast, in the presence of TPB⁻ and no mobile charges could be detected by electrorotation, despite their strong membrane adsorption. Our data suggest that the presence of oxygen atoms in the outer molecular shell is an important factor for the fast translocation ability of lipophilic anions.     

Delivery of floxuridine derivatives to cancer cells by water-soluble organometallic cages

The self-assembly of 2,4,6-tris(pyridin-4-yl)-1,3,5-triazine (tpt) triangular panels with p-cymene (pPr(i)C(6)H(4)Me) ruthenium building blocks and 2,5-dioxydo-1,4-benzoquinonato (dobq) or 5,8-dioxydo-1,4-naphthoquinonato (donq) bridges, in the presence of a pyrenyl-nucleoside derivatives (pyreneR), affords the triangular prismatic host-guest compounds [(pyrene-R)?Ru(6)(pPr(i)C(6)H(4)Me)(6)(tpt)(2)(dobq)(3)](6+) ([(pyrene-R)?1](6+)) and [(pyrene-R)?Ru(6)(pPr(i)C(6)H(4)Me)(6)(tpt)(2)(donq)(3)](6+) ([(pyrene-R)?2](6+)), respectively. The inclusion of six monosubstitutedpyrenyl-nucleosides (pyrene-R1 = 5'-(1-pyrenyl butanoate)-2'-deoxyuridine, pyrene-R2 = 5-fluoro-5'-(1-pyrenyl butanoate)-2'-deoxyuridine, pyrene-R3 = 5'-{N-[1-oxo-4-(1-pyrenyl)butyl]-glycyl}-2'-deoxyuridine, pyrene-R4 = 5-fluoro-5'-{N-[1-oxo-4-(1-pyrenyl)butyl]-glycyl}-2'-deoxyuridine, pyrene-R5 = 5-fluoro-5'-{N-[1-oxo-4-(1-pyrenyl)butyl]-phenylalanyl}-2'-deoxyvuridine, pyrene-R6 = 5-fluoro-5'-{N-[1-oxo-4-(1-pyrenyl)butyl]-phenylalanyl}-2'-deoxyuridine) has been accomplished. The carceplex nature of [(pyrene-R)?1](6+) with the pyrenyl moiety firmly encapsulated in the hydrophobic cavity of the cage with the nucleoside groups pointing outward was confirmed by NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS), while the host-guest nature of [(pyrene-R)?2](6+) was studied in solution by NMR techniques. In contrast to the floxuridine compounds used in the clinic, the host-guest complexes are highly water-soluble. Consequently, the cytotoxicities of these water-soluble compounds have been established using human ovarian A2780 and A2780cisR cancer cells. All the host-guest systems are more cytotoxic than the empty cages alone [1][CF(3)SO(3)](6) (IC(50) = 23 μM) and [2][CF(3)SO(3)](6) (IC(50) = 10 μM), the most active compound [pyrene-R4?1][CF(3)SO(3)](6)being 2 orders of magnitude more cytotoxic (IC(50) = 0.3 μM) on these human ovarian cancer cell lines (A2780 and A2780cisR).     

Evaluation of substituted oxime ethers for growth regulatory activity against Spodoptera litura (F.)

Insect growth regulatory activity (IGR) of fifty-two substituted oxime ethers were evaluated against an important polyphagous lepidopteran crop pest, Spodoptera litura (F.). A number of compounds produced symptoms comparable to exogenously applied juvenile hormone. Maximum IGR activity was exhibited by 4'-(2,6,6-trimethyl-2-cyclohexen- -yl)-3'-buten-2'(E)-ketoxime-N-O-alkyl ether with an ED50 (morphological) of 40 microg g(-1) body weight, compared to 20 microg g(-1) of JH III. Two more compounds namely 4'-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3'-buten-2'(Z)-ketoxime-N-O-methyl propyl ether (ED50 192 microg g(-1)) and 4'-(2,6,6-trimethyl-1-cyclohexen-1-yl)-3'-buten-2'(E)-ketoxime-N-O-pentyl ether (ED50 380 microg g(-1)) showed considerable IGR activity, whereas 4'-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3'-buten-2'(E)-ketoxime-N-O-pentyl ether was found to be toxic to the larvae (ED50 268 microg g(-1)). Three compounds used in this study were also synergised by piperonyl butoxide (PBO). The synergistic ratios were found in the range of 1.33 to 4.605. The ovicidal activity of the oxime ethers is not significant.     

Evaluation of substituted oxime ethers for growth regulatory activity against Spodoptera litura (Lepidoptera: Noctuidae)

Insect growth regulator (IGR) activity of 52 substituted oxime ethers was evaluated against an important polyphagous lepidopteran pest, Spodoptera litura (F.) (Lepidoptera: Noctuidae). Several compounds produced symptoms comparable to exogenously applied juvenile hormone. Maximum ICR activity was exhibited by 4'-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3'-buten-2'(E)-ketoxime-N-O-alkyl ether with an ED50 (morphological) of 40 microg g(-1) body weight, compared with 20 microg g(-1) of juvenile hormone (JH) III. Two more compounds, namely, 4'-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3'-buten-2'(Z)-ketoxime-N-O-methyl propyl ether (ED50 of 192 microg g(-1)) and 4'-(2,6,6-trimethyl-1-cyclohexen-1-yl)-3'-buten-2'(E)-ketoxime-N-O-pentyl ether (ED50 of 380 microg g(-1)) showed considerable IGR activity, whereas 4'-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3'-buten-2'(E)-ketoxime-N-O-pentyl ether was found to be acutely toxic to larvae (ED50 of 268 microg g(-1)). Three compounds used in this study also were synergized by piperonyl butoxide. Synergistic ratios ranged from 1.330 to 4.605. No significant ovicidal activity was obtained.     

Studies towards synthesis of dinucleoside arylphosphonates with metal complexing properties

An efficient and stereospecific synthesis of dinucleoside 4'-(2,2':6',2'-terpyridyl)phosphonate 2 and 5-(2,2'-bipyridyl)phosphonate 3 via a palladium(0) cross coupling strategy has been developed.     

Copper complex-assisted DNA hybridization

2,2'-Bipyridine (bpy) or 1,10-phenanthroline (phen) metal-binding domains were covalently attached to oligonucleotides, and the influence of metal ions on the hybridization of the conjugates was investigated. Metal-binding domains were attached to oligonucleotides at 3'- and 5'-terminal positions, thus placing them in juxtaposed positions after hybridization to a common target strand. While the ligands alone had a positive effect (increased Tm) on hybrid stability, the duplex was further stabilized by the addition of copper(I) and/or copper(II) through the formation of a metal complex in which the two short sequences are linked through {Cu(bpy)2}, {Cu(phen)}, or {Cu(bpy)(phen)} domains. The increase in Tm, due to formation of the {Cu(bpy)2}, {Cu(phen)2}, {Cu(bpy)(phen)} motifs is reversed upon addition of EDTA, consistent with the stripping of copper from the ligands. The effect of metal complex formation on the duplex strength was shown to be highest if the two metal-coordinating ligand strands are placed as close to each other as possible.     

Expected distance between terminal nucleotides of RNA secondary structures

In "The ends of a large RNA molecule are necessarily close", Yoffe et al. (Nucleic Acids Res 39(1):292-299, 2011) used the programs RNAfold [resp. RNAsubopt] from Vienna RNA Package to calculate the distance between 5' and 3' ends of the minimum free energy secondary structure [resp. thermal equilibrium structures] of viral and random RNA sequences. Here, the 5'-3' distance is defined to be the length of the shortest path from 5' node to 3' node in the undirected graph, whose edge set consists of edges {i, i + 1} corresponding to covalent backbone bonds and of edges {i, j} corresponding to canonical base pairs. From repeated simulations and using a heuristic theoretical argument, Yoffe et al. conclude that the 5'-3' distance is less than a fixed constant, independent of RNA sequence length. In this paper, we provide a rigorous, mathematical framework to study the expected distance from 5' to 3' ends of an RNA sequence. We present recurrence relations that precisely define the expected distance from 5' to 3' ends of an RNA sequence, both for the Turner nearest neighbor energy model, as well as for a simple homopolymer model first defined by Stein and Waterman. We implement dynamic programming algorithms to compute (rather than approximate by repeated application of Vienna RNA Package) the expected distance between 5' and 3' ends of a given RNA sequence, with respect to the Turner energy model. Using methods of analytical combinatorics, that depend on complex analysis, we prove that the asymptotic expected 5'-3' distance of length n homopolymers is approximately equal to the constant 5.47211, while the asymptotic distance is 6.771096 if hairpins have a minimum of 3 unpaired bases and the probability that any two positions can form a base pair is 1/4. Finally, we analyze the 5'-3' distance for secondary structures from the STRAND database, and conclude that the 5'-3' distance is correlated with RNA sequence length.     

Polyazacyclophanes incorporating two pyridine units and a heteroaromatic pendant group as potential cleaving agents of mRNA 5'-cap structure

Four hexaazacyclophanes, 16a-d, incorporating two pyridine units and a (pyridin-2-yl)methyl or (quinolin-2-yl)methyl pendant group at one of the ring N-atoms have been prepared. The key step of the synthesis is an intermolecular cyclization of N,N-bis{[6-(tosyloxymethyl)pyridin-2-yl]methyl}-2-nitrobenzenesulfonamide (7) with either tert-butyl bis{2-[(2-nitrophenylsulfonyl)amino]ethyl}carbamate (2a) or tert-butyl bis{3-[(2-nitrophenylsulfonyl)amino]propyl}carbamate (2b) in the presence of anhydrous Cs(2)CO(3). Removal of the acid-labile tert-butoxycarbonyl protection then allows attachment of the pendant group by reductive alkylation to the exposed secondary amino group, and deprotection of the remaining aliphatic ring N-atoms completes the synthesis. The ability of the cyclophanes and their dinuclear Cu(2+) and Zn(2+) complexes to cleave the mRNA cap structure, m(7)G(5')pppG(5') (1), has been studied.     

Synthesis of 2-bromomethyl-3-hydroxy-2-hydroxymethyl-propyl pyrimidine and theophylline nucleosides under microwave irradiation. Evaluation of their activity against hepatitis B virus

Alkylation of 2-methylthiopyrimidin-4(1H)-one (1a) and its 5(6)-alkyl derivatives 1b-d as well as theophylline (7) with 2,2-bis(bromomethyl)-1,3-diacetoxypropane (2) under microwave irradiation gave the corresponding acyclonucleosides 1-[(3-acetoxy-2-acetoxymethyl-2-bromomethyl)prop-1-yl]-2-methyl-thio pyrmidin-4(1H)-ones 3a-d and 7-[(3-acetoxy-2-acetoxymethyl-2-bromomethyl)prop-1-yl]theophylline (8), which upon further irradiation gave the double-headed acyclonucleosides 1,1 '-[(2,2-diacetoxymethyl)-1,3-propylidene]-bis[(2-(methylthio)-pyrimidin-4(1H)-ones] 4a-c, and 7,7 '-[(2,2-diacetoxymethyl)-1,3-propylidene]-bis(theophylline) (9). The deacetylated derivatives were obtained by the action of sodium methoxide. The activity of deacetylated nucleosides against Hepatitis B virus was evaluated. Compound 5b showed moderate inhibition activity against HBV with mild cytotoxicity.     

Two types of calcium-dependent channels of potassium outward current in the somatic membrane of Helix pomatia neurons

Characteristics of delayed potassium outward current were investigated during voltage clamp experiments on nonidentified intracellularly perfused neurons isolated from the snailHelix pomatia. A calcium-dependent potassium curent displaying special properties was shown to exist, apart from the voltage-operated potassium currents dependent on intracellular calcium ions . This type of current increases with a rise in the extracellular concentration of calcium ions , is not blocked by intracellular application of 10 mM EGTA and 77 mM fluoride, and may be suppressed by adding 1.5 mM cobalt ions to the extracellular fluid. This current, unlike , only takes a few milliseconds to peak, after which it fades to a steady level, comparable with that of .A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 19, No. 2, pp. 185–191, March–April, 1987.     

Novel azolyl-(phenylmethyl)]aryl/heteroarylamines: potent CYP26 inhibitors and enhancers of all-trans retinoic acid activity in neuroblastoma cells

The synthesis and potent inhibitory activity of novel 4-[(imidazol-1-yl and triazol-1-yl)(phenyl)methyl]aryl-and heteroaryl amines versus a MCF-7 CYP26A1 cell assay is described. Biaryl imidazole ([4-(imidazol-1-yl-phenyl-methyl)-phenyl]-naphthalen-2-yl-amine (8), IC(50)=0.5 microM; [4-(imidazol-1-yl-phenyl-methyl)-phenyl]-indan-5-yl-amine (9), IC(50)=1.0 microM) and heteroaryl imidazole derivatives ((1H-benzoimidazol-2-yl)-{4-[(5H-imidazol-1-yl)-phenyl-methyl]-phenyl}-amine (15), IC(50)=2.5 microM; benzooxazol-2-yl-{4-[(5H-imidazol-1-yl)-phenyl-methyl]-phenyl}-amine (16), IC(50)=0.9 microM; benzothiazol-2-yl-{4-[(5H-imidazol-1-yl)-phenyl-methyl]-phenyl}-amine (17), IC(50)=1.5 microM) were the most potent CYP26 inhibitors. Using a CYP26A1 homology model differences in activity were investigated. Incubation of SH-SY5Y human neuroblastoma cells with the imidazole aryl derivative 8, and the imidazole heteroaryl derivatives 16 and 17 potentiated the atRA-induced expression of CYP26B1. These data suggest that further structure-function studies leading to clinical development are warranted.     

Inhibitory effect on NO production of phenolic compounds from Myristica fragrans

Three new phenolics: ((7S)-8'-(benzo[3',4']dioxol-1'-yl)-7-hydroxypropyl)benzene-2,4-diol (1), ((7S)-8'-(4'-hydroxy-3'-methoxyphenyl)-7-hydroxypropyl)benzene-2,4-diol (2) and ((8R,8'S)-7-(4-hydroxy-3-methoxyphenyl)-8'-methylbutan-8-yl)-3'-methoxybenzene-4',5'-diol (3), along with four known compounds (4-7) were isolated from the seeds of Myristica fragrans. Their chemical structures were established mainly by 1D and 2D NMR techniques and mass spectrometry. Their anti-inflammatory activity was evaluated against LPS-induced NO production in macrophage RAW264.7 cells.     

Gel-based oligonucleotide microarray approach to analyze protein-ssDNA binding specificity

Gel-based oligonucleotide microarray approach was developed for quantitative profiling of binding affinity of a protein to single-stranded DNA (ssDNA). To demonstrate additional capabilities of this method, we analyzed the binding specificity of ribonuclease (RNase) binase from Bacillus intermedius (EC 3.1.27.3) to ssDNA using generic hexamer oligodeoxyribonucleotide microchip. Single-stranded octamer oligonucleotides were immobilized within 3D hemispherical gel pads. The octanucleotides in individual pads 5'-{N}N(1)N(2)N(3)N(4)N(5)N(6){N}-3' consisted of a fixed hexamer motif N(1)N(2)N(3)N(4)N(5)N(6) in the middle and variable parts {N} at the ends, where {N} represent A, C, G and T in equal proportions. The chip has 4096 pads with a complete set of hexamer sequences. The affinity was determined by measuring dissociation of the RNase-ssDNA complexes with the temperature increasing from 0 degrees C to 50 degrees C in quasi-equilibrium conditions. RNase binase showed the highest sequence-specificity of binding to motifs 5'-NNG(A/T/C)GNN-3' with the order of preference: GAG > GTG > GCG. High specificity towards G(A/T/C)G triplets was also confirmed by measuring fluorescent anisotropy of complexes of binase with selected oligodeoxyribonucleotides in solution. The affinity of RNase binase to other 3-nt sequences was also ranked. These results demonstrate the applicability of the method and provide the ground for further investigations of nonenzymatic functions of RNases.     

Esr Spectra of Radicals of Single-Stranded and Double-Stranded DNA in Aqueous Solution. Implications for Oh-Induced Strand Breakage

In situ photolysis at 20^oC (argon plasma light source, $, $ 200 mm) of oxygen-free solutions containing 2mM H₂0₂ and heat-denatured, single-stranded (sS)DNA from calf-thymus resulted in the ESR spectra of the 6-hydroxy-5,6-dihydro-thymin-5-yl {1} and 5-methyleneuracil {3} radicals linked to the sugar-phosphate backbone. They were generated by reaction of OH radicals with DNA. By comparison of the decay characteristics of the ESR signals with rate constants from pulse-conductivity measurements [E. Bothe, G.A. Qureshi and D. Schulte-Frohlinde, Z. Naturforsch. 38c 1030, (1983)] the thymine-derived radicals {1} and {3} can be excluded as precursors of the fast, dominating component of strand breakage of ssDNA. In the absence of H₂0₂ from native, doubie-stranded (ds)DNA an ESR signal was obtained (singlet, g ～ 2.004, $1/2 ～ 0.8 mT) which was assigned to the deprotonated guanine radical cation, {G'(-H)} of a DNA subunit. It is assumed that by the UV irradiation the guanine radical cation, {G⁺}, is generated, either by monophotonic photoionisation or by electron transfer to pyrimidine bases. By rapid transfer of the bridging proton from {G⁺} to the hydrogen bonded cytosine {G'(-H)} is formed. When photolysis of dsDNA was carried out in the presence of H₂0₂, reaction of photolytically generated OH resulted in peroxyl radicals and purine radicals. The oxygen for formation of the peroxyl radicals is probably produced by reaction of {G' (-H)} with H₂0₂. Photolysis of N₂0-saturated solutions containing dsDNA or ssDNA provided another possibility of generation of OH radicals. Under those conditions the OH-induced radicals {1} and {3} were obtained not only from ssDNA but also from dsDNA.     

Studies of peptide antibiotics. XLIV. Syntheses and biological activities of gramicidin S analogs containing delta-hydroxy-L-norvaline or glycine

The antibiotic gramicidin S (GS) has the structure of cyclo (-L-Val1-L-Orn2-L-Leu3-D-Phe4-L-Pro5-L-Val1'-L-Orn2'-L-Leu3'-D-Phe4'-L-Pro5'-) and is basic in character. Five GS analogs including [Gly1,1']-GS and the neutral [L-Hnv2,2']-GS (Hnv represents delta-hydroxynorvaline) were synthesized by the solid-phase method to evaluate the role of L-Val1,1' and L-Orn2,2' residues in GS. The hybrid analogs [( Gly1]-GS and [L-Hnv2]-GS) and [D-Tyr4,4']-GS showed high antibacterial activities, whereas [Gly1,1']-GS and [L-Hnv2,2']-GS possessed no activity. Inhibitory effects by these analogs for the adsorption of 14C-labeled GS on cells of bacteria sensitive to GS were determined. The structure-activity relationship of GS is discussed on the basis of the results on these GS analogs.     

Phosphorothioate analogues of (2'-5')(A)4: agonist and antagonist activities in intact cells

Metabolically stable phosphorothioate tetramer analogues of (2'-5')(A)n with Rp and/or Sp chirality in the 2'-5'-phosphodiester linkages constitute a new class of antiviral agents since they mimic the effects of interferons. Three of the diastereomeric 5'-monophosphates (i.e., pRpRpRp, pSpRpRp, and pRpSpSp) bind to and activate RNase L from extracts of HeLa cells. However, the pSpSpSp (2'-5')-(A)4-phosphorothioate is unique in that it binds to, but cannot activate, RNase L to cleave rRNA. When microinjected into the cytoplasm of HeLa cells followed by virus infection, the pRpRpRp, pSpRpRp, and pRpSpSp (2'-5')(A)4-phosphorothioates demonstrate antiviral activity, as does (2'-5')(A)4ox-red, an active (2'-5')(A)n analogue. When microinjected simultaneously with (2'-5')(A)nox-red, an active the pSpSpSp (2'-5')(A)4-phosphorothioate inhibits activation of RNase L in HeLa cells, thereby blocking direct protection of vesicular stomatitis virus. The agonist and antagonist properties of pRpRpRp and pSpSpSp, respectively, are transient probably as a consequence of the hydrolysis of the 5'-monophosphate and formation of the less active (2'-5')(A)4-phosphorothioate cores. The possible use of these (2'-5')(A)4-phosphorothioates as tools for dissecting the biological significance of the (2'-5')(A)n system or in antiviral chemotherapy is discussed.     

Geranyl chalcone derivatives with antifungal and radical scavenging properties from the leaves of Artocarpus nobilis

Antifungal activity guided fractionation of the n-butanol extract from the methanol extract of the leaves of Artocarpus nobilis furnished 2',4',4-trihydroxy-3'-geranylchalcone (1), 2 ',4',4-trihydroxy-3'-[6-hydroxy-3,7-dimethyl-2(E),7-octadienyl]chalcone (2), 2',4',4-trihydroxy-3'-[2-hydroxy-7-methyl-3-methylene-6-octaenyl]chalcone (3), 2',3,4,4'-tetrahydroxy-3'-geranylchalcone (4), 2',3,4,4'-tetrahydroxy-3'-[6-hydroxy-3,7-dimethyl-2(E),7-octadienyl]chalcone (5). The chalcones 3 and 5 are new natural products whereas 1 and 2 are reported first time from the family Moraceae. All these compounds showed good fungicidal activity against Cladosporium cladosporioides and high radical scavenging activity towards the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical in TLC bio-autography method.     

Geranyl flavonoids from the leaves of Artocarpus altilis

Five geranyl dihydrochalcones, 1-(2,4-dihydroxyphenyl)-3-{4-hydroxy-6,6,9-trimethyl-6a,7,8,10a-tetrahydro-6H-dibenzo[b,d]pyran-5-yl}-1-propanone (2), 1-(2,4-dihydroxyphenyl)-3-[3,4-dihydro-3,8-dihydroxy-2-methyl-2-(4-methyl-3-pentenyl)-2H-1-benzopyran-5-yl]-1-propanone (4), 1-(2,4-dihydroxyphenyl)-3-[8-hydroxy-2-methyl-2-(3,4-epoxy-4-methyl-1-pentenyl)-2H-1-benzopyran-5-yl]-1-propanone (5), 1-(2,4-dihydroxyphenyl)-3-[8-hydroxy-2-methyl-2-(4-hydroxy-4-methyl-2-pentenyl)-2H-1-benzopyran-5-yl]-1-propanone (8), and 2-[6-hydroxy-3,7-dimethylocta-2(E),7-dienyl]-2',3,4,4'-tetrahydroxydihydrochalcone (9), along with four known geranyl flavonoids (1, 3, 6, 7), were isolated from the leaves of Artocarpus altilis. Their structures were established by spectroscopic means and by comparison with the literature values. Compounds 2, 4, and 9 exhibited moderate cytotoxicity against SPC-A-1, SW-480, and SMMC-7721 human cancer cells.