Effects of diterpene esters of tigliane,daphnane, ingenane,and lathyrane types on pink bollworm,Pectinophora gossypiella saunders (Lepidoptera: Gelechiidae)

Twenty esters, representing the biogenetically related tigliane, daphnane, ingenane, and lathyrane series of diterpenes, were screened for growth-inhibitory and insecticidal effects on newly hatched larvae of the North American cotton pest,Pectinophora gossypiella (pink bollworm). Among the tigliane derivatives tested, only 12-O-tetradecanoylphorbol-13-acetate and 12-O-(2-methyl)butyrylphorbol-13-decanoate, of seven phorbol diesters isolated from croton oil by a new procedure involving droplet countercurrent chromatography, were active againstP.gossypiella as both growth inhibitors and insecticides. The effects of the former compound were not significantly diminished by acetylation of its C-20 primary hydroxy group. Three other croton oil phorbol diester constituents, as well as daphnetoxin and daphnetoxin-5,20-diacetate, exhibited activity as growth inhibitors, but not as insecticidal agents, at the doses used. None of the ingenane or lathyrane derivatives investigated was active in either respect. 12-0-Tetradecanoylphorbol-13-acetate was found to cause 100% mortality on second-stadium larvae ofCulex pipiens at 0.6 ppm, but exhibited less significant effects onOncopeltus fasciatus (second-stadium nymphs) andTribolium confusion (adults) when applied at higher doses.     

Reaction of α-tocopherol with alkyl and alkylperoxyl radicals of methyl linoleate

α-Tocopherol was reacted with alkyl and alkylperoxyl radicals at 37°C in bulk phase. The lipid-free radicals were generated by the reaction of methyl linoleate with the free radical initiator, 2,2′-azobis(2,4-dimethylvaleronitrile) (AMVN) under air-insufficient conditions. The products were isolated by high-performance liquid chromatography. Their structures were identified as 2-(α-tocopheroxy)-2,4-dimethylvaleronitrile (1), a mixture of methyl 9-(8a-peroxy-α-tocopherone)-10(E),12(Z)-octadecadienoate and methyl 13-(8a-peroxy-α-tocopherone)-9(Z),11(E)-octadecadienoate (2), methyl 9-(α-tocopheroxy)-10(E),12(Z)-octadecadienoate (3a), methyl 13-(α-tocopheroxy)-9(Z),11(E)-octadecadienoate (3b), α-tocopherol spirodiene dimer (4) and α-tocopherol trimer (5). When methyl linoleate containing α-tocopherol was oxidized with AMVN under airsufficient conditions, the main products were 8a-alkyl-peroxy-α-tocopherones (2). In addition to these compounds, 6-O-alkyl-α-tocopherols (1, 3a and 3b) were formed when the reaction was carried out under air-insufficient conditions. The results indicate that α-tocopherol can react with both alkyl and alkylperoxyl radicals during the autoxidation of polyunsaturated lipids.     

Potential bile acid metabolites. 24. An efficient synthesis of carboxyl-linked glucosides and their chemical properties

A facile and efficient synthesis of the carboxyl-linked glucosides of bile acids is described. Direct esterification of unprotected bile acids with 2,3,4,6-tetra-O-benzyl-d-glucopyranose in pyridine in the presence of 2-chloro-1,3,5-trinitrobenzene as a coupling agent afforded a mixture of the α- and β-anomers (ca. 1∶3) of the 1-O-acyl-d-glucoside benzyl ethers of bile acids, which was separated effectively on a C₁₈ reversedphase chromatography column (isolated yields of α- and β-anomers are 4–9% and 12–19%, respectively). Subsequent hydrogenolysis of the α- and β-acyl glucoside benzyl ethers on a 10% Pd−C catalyst in acetic acid/methanol/EtOAc (1∶2∶2, by vol) at 35°C under atmospheric pressure gave the corresponding free esters in good yields (79–89%). Chemical specificities such as facile hydrolysis and transesterification of the acyl glucosides in various solvents were also discussed.     

Reaction of lipids containing hydroxy groups with trimethylsulfonium hydroxide: Formation ofO-methyl derivatives

Base-catalyzed transesterification of acyl lipids with trimethylsulfonium hydroxide (TMSH) is an easy and convenient method for the preparation of fatty acid methyl esters (FAME) for gas chromatography (GC) analyses. We have found, however, that lipids containing hydroxy groups are partially converted to the correspondingO-methyl ether derivatives which may interfere with FAME in GC separations. For example, long-chain alcohols are found to be converted to alkyl methyl ethers,rac-1-O-alkylglycerols to the corresponding 2-O-and 3-O-monomethyl ethers, as well as 2,3-di-O-methyl ethers, hydroxy fatty acids to methoxy FAME, and cholesterol to cholesteryl 3β-methyl ether. From our results, it is obvious that TMSH derivatization method is not recommended without limitation for lipids containing hydroxy groups; it may be, however, of some diagnostic value for the analysis of such lipids by GC/mass spectrometry.     

O-alkyl diolO-,S- andSe-phosphoroamidates of DL-α-tocopherol and their dimethylaminoalkyl derivatives as diester and triester models of phospholipids

Hexamethyltriamide of phosphorous acid, activated by addition of iodine at an optimal molar ratio of 1.05∶0.05, was used as a phosphorylating reagent to synthesize 1-hexadecyloxyethyl-2-O-, 1-hexadecyloxypropyl-3-O-, and 1-hexadecyloxybutyl-4-O-(DL-α-tocopheryl-6-O)-(N,N-dimethylamido)selenophosphate,-thiophosphate and-phosphate derivatives, and some of their 2-dimethyl-aminoethyl-1-O-, and 3-dimethylaminopropyl-1-O-triester analogues in a “one-pot procedure” in overall yields of 69–87%. Activation of the reaction with an equimolar mixture of imidazole and carbon disulfide at the triester formation step permits selective phosphorylation at room temperature. The compounds synthesized represent new diester and triester models containing alkyl ether diolphospholipid structures.     

New glyceroglycolipid and ceramide from <Emphasis Type="Italic">Premna microphylla</Emphasis>

Iwo new compounds (1,2) were isolated from the ethanolic extract of the leaves of Premna microphylla, together with five known compounds. The structures of compounds 1 and 2 were elucidated as (2S,3S,4R,11E)-2-[(2R)-2-hydroxytetracosanoylamino]-11-octadecene-1,3,4-triol (1) and 1-O(9Z,12Z, 15Z-octadecatrienoyl)-3-O-[β-d-galactopyranosyl-(1→6)-O-β-d-galactopyranosyl-(1→6)-α-d-galactopyranosyl] glycerol (2) by means of spectroscopic and chemical methods.     

Antioxidant activities of major components of γ-oryzanol from rice bran using a linoleic acid model

The change in hydroperoxides of linoleic acid incubated with constant micro air flow at 37°C was used to evaluate the antioxidant activities of three major components of γ-oryzanol from rice bran (cycloartenyl ferulate, 24-methylene cycloartanyl ferulate, and campesteryl ferulate) compared with α-tocopherol and ferulic acid. The four hydroperoxide isomers of linoleic acid, 9-hydroperoxy-10-trans, 12-cis-octadecadienoic acid [9HPODE(t,c)], 9-hydroperoxy-10-trans, 12-trans-octadecadienoic acid, 13-hydroperoxy-9-cis, 11-trans-octadecadienoic acid [13HPODE(c,t)], and 13-hydroperoxy-9-trans, 11-trans-octadecadienoic acid, were measured using normal-phase high-performance liquid chromatography with an ultraviolet detector. The three components of γ-oryzanol evidenced significant antioxidant activity when they were mixed with linoleic acid in a molar ratio of 1∶100 and 1∶250 but not in a molar ratio of 1∶500 (P<0.05). α-Tocopherol and ferulic acid also demonstrated significant antioxidant activity at all three molar ratios (P<0.05). The highest molar ratio (1∶100) of α-tocopherol, however, caused greater levels of 9HPODE(t,c) and 13HPODE(c,t) than the other two less concentrated treatments.     

Lipase-catalyzed monoesterification of 1-O-hexadecylglycerol in organic solvents

A simple method is presented to esterify 1-O-hexadecyl-rac-glycerol using lipases in different organic solvents. The following fatty acids were used: C_14∶0, C_16∶0, C_18∶0, C_18∶1, and C_18∶2. Monoesterification was achieved by using a limiting amount of the fatty acid. Both the 1-O-hexadecyl-3-O-acylglycerol and the 2-O-acylglycerol were obtained in a total yield of 75% and a ratio of 7∶1 in dichloromethane after 3 d. Chromatographic data for the monoesters, useful for the identification of the natural products, are given (gas-liquid chromatography, thin-layer chromatography, reverse-phase thin-layer chromatography). The structure was confirmed by a chemical synthesis of 1-O-hexadecyl-2-O-hexadecanoylglycerol. The 3-O-glyceride was also formed by acyl migration, as the minor component. The monoesters were separated by column chromatography and characterized by ¹H and ¹³C nuclear magnetic resonance spectra.     

Inhibition of malonaldehyde formation by antioxidants from ω3 polyunsaturated fatty acids

The inhibitory effect of α-tocopherol, β-carotene, 2″-O-glycosyl isovitexin (2″-O-GIV), and butylated hydroxytoluene (BHT) on malonaldehyde (MA) formation from ω3 polyunsaturated fatty acids (PUFA) was determined by gas chromatography. The levels of MA formed from 1 mg each of octadecatetraenoic acid (ODTA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) upon oxidation with Fenton's reagent were 29.8±1.5, 17.2±1.5, and 22.0±0.7 nmol, respectively. BHT was most effective toward protecting all three ω3 PUFA, whereas β-carotene did not exhibit any inhibitory effect. 2″-O-GIV inhibited MA formation from EPA and DHA by 56 and 43%, respectively, showing the second greatest inhibitory activity after BHT. α-Tocopherol inhibited MA formation from ODTA and DHA by 67 and 28%, respectively, but it did not show any activity toward EPA oxidation. The naturally occurring antioxidant, 2″-O-GIV, may be useful to prevent oxidation of ω3 PUFA.     

Autoxidation of linoleic acid and behavior of its hydroperoxides with and without tocopherols

The autoxidation of linoleic acid dispersed in an aqueous media and the effect of α-, γ- and δ-tocopherols were studied. The quantitative analysis of the hydroperoxide isomers (13-cis,trans; 13-trans,trans; 9-trans,cis; 9-trans,trans) by direct high-performance liquid chromatography exhibited a prooxidant activity of α-tocopherol at high concentration (3.8% by weight of linoleic acid). On the other hand, α-tocopherol at lower concentrations (0.38 and 0.038%) and γ- and δ-tocopherols at high concentration (3.8%) were antioxidant. Furthermore, the addition of tocopherols modified the distribution of the geometrical isomers. The formation of thetrans,trans hydroperoxide isomers was completely inhibited by the highest concentration of the three tocopherols independently of their antioxidant or prooxidant activity and only delayed by the lower concentrations of α-tocopherol. The addition of tocopherols to hydroperoxide isomers reduced the decomposition rate of these isomers in the order α-tocopherol < γ-tocopherol < δ-tocopherol for thecis,trans hydroperoxide isomer and α-tocopherol ≪ γ-tocopherol ⋍ δ-tocopherol for thetrans,trans hydroperoxide isomer. With these hydroperoxides, as during linoleic acid autoxidation, α-tocopherol was completely oxidized whatever its initial concentration, while γ-tocopherol underwent partial oxidation and δ-tocopherol was practically unchanged.     

Identification of two novel dihydroxysterols fromPavlova

Pavlova gyrans andP. lutheri were cultured, and the dihydroxysterols were isolated from the free sterol and the polar sterol fractions. Four dihydroxysterols were detected in amounts greater than 1% of total sterol by gas chromatography and were analyzed by gas chromatography/mass spectrometry. The two principal sterols were isolated by chromatography on alumina followed by hydrophobic Sephadex column chromatography. The two sterols appeared to differ by having either a methyl or an ethyl group at C−24; they were termed “methylpavlovol” and “ethylpavlovol.” Analysis by 400 MHz nuclear magnetic resonance showed that methylpavlovol is 4α,24β-dimethylcholestan-3β,4β-diol and ethylpavlovol is 4α-methyl,24β-ethylcholestan-3β,4β-diol. The 4α-methyl,4β-hydroxy configuration has not been observed previously in a natural sterol. Dihydroxysterols make up approximately one-third of the total sterols in thesePavlova species. Neither the biosynthetic origin of these dihydroxysterols nor their role in the biochemistry ofPavlova is known.     

Further studies on sphingolipids in wheat grain

The principal molecular species of sphingolipids in wheat grain were confirmed to beN-2′-hydroxylignoceroyl-4-hydroxysphinganine for ceramide, and 1-O-β-glucosyl-, 1-O-[β-mannosyl(1→4)-O-β-glucosyl]-, 1-O-[β-mannosyl(1→4)-O-β-mannosyl(1→4)-O-β-glucosyl]-and 1-O[β-mannosyl(1→4)-O-β-mannosyl(1→4)-O-β-mannosyl(1→4)-O-β-glucosyl]-N-2′-hydroxypalmitoyl (or hydroxyarachidoyl)-cis-8-sphingenine for mono-, di-, tri- and tetraglycosylceramide, respectively. A novel glycolipid, cellobiosylceramide, was found as the minor diglycosylceramide; the major species was characterized to be 1-O-[β-glucosyl(1→4)-O-β-glucosyl]-N-2′-hydroxypalmitoyl (or hydroxyarachidoyl)-cis-8-sphingenine. It was observed in these sphingolipids that the dihydroxy bases were combined mainly with C₁₆ and C₂₀ acids, whereas the trihydroxy bases combined mostly with acids of chain length of 20 or more.     

A Feeding Stimulant for Manduca sexta from Solanum surattenses

The acceptance of Solanum surattenses as a host plant for the larvae of Manduca sexta was explained by the presence of feeding stimulants in foliage. Bioassay-guided fractionation of plant extracts resulted in the isolation of a highly active compound (1), which was identified as a furostan derivative {26-O-β-d-glucopyranosyl-(25R)-furosta-5-ene-3-β-yl-O-α-l-rhamnopyranosyl-(1″-2′)-O-α-l-rhamnopyranosyl-(1′″-3″)-O-β-d-glucopyranoside}. This compound has the same steroidal core substructure as that in a stimulant (indioside D) previously identified from potato foliage. However, the sugar substituents attached to the core are different.     

Chromatographic separation of the stereoisomers of α-tocopherol

The diastereoisomers of2-ambo-α-tocopherol were completely separated as TMS ethers by gas chromatography on a 115 m × 0.25 mm glass capillary column coated with SP2340, at a column temperature of 195 C. In the same way,all-rac-α-tocopherol was separated into four peaks, corresponding to the four racemates present, and having the same retention ratios as the four diastereoisomers of 4′-ambo-8′-ambo-α-tocopherol (produced by the hydrogenation of natural α-tocotrienol). Retention data and relative peak areas for the diastereoisomers of the synthesized α-tocopherols and several commercial products were determined. Limited data on the isomers of other tocopherols also are reported.     

New Nortriterpenoid and Ceramides From Stems and Leaves of Cultivated <Emphasis Type="Italic">Triumfetta cordifolia</Emphasis> A Rich (Tiliaceae)

To highlight the role of plants in traditional healing, the leaves and the stems of cultivated Triumfetta cordifolia were phytochemically studied yielding a new nor-ursane type (1), a new ceramide (2) and a new piperidinic ceramide derivative (3) named, respectively, 2α,19α-dihydroxy-3-oxo-23-nor-urs-12-en-28-oic acid, (2R)-2-hydroxy-N-[(2S,3S,4R,26E)-1,3,4-trihydroxy-26-triaconten-2-yl] tetradecanamide and (2R,8Z)-2-hydroxy-{(2S,3R,5R,6S)-3,5-dihydroxy-6-[(1E,5Z)-hexadeca-1,5-dienyl]-2-(β-d-glucopyranosyloxy)methyl piperidine-1-yl} tetracos-8-enamide (3). These were obtained together with lupeol (4), stigmasterol (5), 3-O-β-d-glucopyranoside of β-sitosterol (6), tormentic acid (7) from stems and heptadecanoic acid (8), β-carotene (9), oleanolic acid (10), and 24-hydroxytormentic acid (11) from leaves. The structures were determined on the basis of NMR data (¹H-, ¹³C-, 2D-NMR analyses), mass spectrometry and confirmed by chemical transformations as well as comparison of spectral data with those reported in the literature. The FRAP method was used to evaluate the antioxidant activity of fractions collected from flash chromatography and isolated compounds. Among the fractions, four reduced Fe^III-TPTZ to Fe^II-TPTZ while isolated pure compounds showed no activity.     

Oxidation products of cyanidin 3-O-β-d-glucoside with a free radical initiator

Recently, we have reported that anthocyanins show strong antioxidative activity, but no attention has been paid to anthocyanins from the viewpoint of the reaction mechanism of alkylperoxyl radicals; therefore, we investigated the reaction products of antioxidative anthocyanins (cyanidin 3-O-β-d-glucoside). Cyanidin 3-O-β-d-glucoside was reacted with 2,2′-azobis(2,4-dimet hylvaleronitrile) to generate the alkylperoxyl radicals, and the reaction products were isolated by high-performance liquid chromatography. The products were identified as 4,6-dihydroxy-2-O-β-d-glucosyl-3-oxo-2,3-dihydrobenzofuran and protocatechuic acid. Based on reaction products, the antioxidative mechanism of cyanidin 3-O-β-d-glucoside may be different from that of α-tocopherol; cyanidin 3-O-β-d-glucoside would produce another radical scavenger, as it would break down the structure and scavenge the radicals.     

Fungal Biotransformation of 2′-Methylflavanone and 2′-Methylflavone as a Method to Obtain Glycosylated Derivatives

Methylated flavonoids are promising pharmaceutical agents due to their improved metabolic stability and increased activity compared to unmethylated forms. The biotransformation in cultures of entomopathogenic filamentous fungi is a valuable method to obtain glycosylated flavones and flavanones with increased aqueous solubility and bioavailability. In the present study, we combined chemical synthesis and biotransformation to obtain methylated and glycosylated flavonoid derivatives. In the first step, we synthesized 2′-methylflavanone and 2′-methylflavone. Afterwards, both compounds were biotransformed in the cultures of two strains of entomopathogenic filamentous fungi Beauveria bassiana KCH J1.5 and Isaria fumosorosea KCH J2. We determined the structures of biotransformation products based on NMR spectroscopy. Biotransformations of 2′-methyflavanone in the culture of B. bassiana KCH J1.5 resulted in three glycosylated flavanones: 2′-methylflavanone 6-O-β-d-(4″-O-methyl)-glucopyranoside, 3′-hydroxy-2′-methylflavanone 6-O-β-d-(4″-O-methyl)-glucopyranoside, and 2-(2′-methylphenyl)-chromane 4-O-β-d-(4″-O-methyl)-glucopyranoside, whereas in the culture of I. fumosorosea KCH J2, two other products were obtained: 2′-methylflavanone 3′-O-β-d-(4″-O-methyl)-glucopyranoside and 2-methylbenzoic acid 4-O-β-d-(4′-O-methyl)-glucopyranoside. 2′-Methylflavone was effectively biotransformed only by I. fumosorosea KCH J2 into three derivatives: 2′-methylflavone 3′-O-β-d-(4″-O-methyl)-glucopyranoside, 2′-methylflavone 4′-O-β-d-(4″-O-methyl)-glucopyranoside, and 2′-methylflavone 5′-O-β-d-(4″-O-methyl)-glucopyranoside. All obtained glycosylated flavonoids have not been described in the literature until now and need further research on their biological activity and pharmacological efficacy as potential drugs.     

Isolation and structure of a new galactolipid from oat seeds

Seeds of oat (Avena sativa L.) were recently shown to contain significant quantities of a new hydroxy acid, (15R)-hydroxy-(9Z)-(12Z)-octadecadienoic acid (trivial name, avenoleic acid). In the present work, avenoleate was found to be mainly (63%) localized in the glycolipid fraction of oat seed lipids. Fractionation of the glycolipids by thin-layer chromatography and reversed-phase high-performance liquid chromatography revealed the presence of a main molecular species which accounted for 20% of the total avenoleate content of oat seeds. Structural studies by chemical methods and mass spectrometry demonstrated that the avenoleate-containing glycolipid was a galactolipid assembled of one molecule of avenoleic acid, two molecules of linoleic acid, two molecules of D-galactose, and one molecule of glycerol. Degradation of the new galactolipid by chemical and enzymatic methods demonstrated the localization of acyl chains, i.e., linoleate at sn-1 and linoleoylavenoleate at sn-2. Nuclear magnetic resonance spectroscopy gave independent support for this structure and also demonstrated that the two galactoses formed an α-d-galactopyranosyl-1-6-β-d-galactopyranosyl moiety which was bound to the sn-3 position. Based on these experiments, the new galactolipid could be formulated as 1-[(9′Z),(12′Z)-octadecadienoyl]-2-[(15″R)-{9″'Z), (12″'Z)-octadecadienoyloxy}-(9″Z),(12″Z)-octadecadienoyl]-3-(α-d-galactopyranosyl-1-6-β-d-galactopyranosyl)-glycerol. Quantitatively, the amount of the avenoleate-containing galactolipid was of the same order of magnitude as those of individual molecular species of digalactosyldiacylglycerol containing nonoxygenated acyl chains. The content of the new galactolipid in oat seeds was 0.5–0.6 mg per g of seed.     

Reaction of α-tocopherol in heated bulk phase in the presence of methyl linoleate (13S)-hydroperoxide or methyl linoleate

α-Tocopherol and methyl (9Z, 11E)-(S)-13-hydroperoxy-9, 11-octadecadienoate (13-MeLOOH) were allowed to stand at 100°C in bulk phase. The products were isolated and identified as methyl 13-hydroxyoctadecadienoate (1), stereoisomers of methyl 9,11,13-octadecatrienoate (2), methyl 13-oxo-9, 11-octadecadienoate (3), epoxy dimers of methyl linoleate with an ether bond (4), a mixture of methyl (E)-12, 13-epoxy-9-(α-tocopheroxy)-10-octadecenoates and methyl (E)-12, 13-epoxy-9-(α-tocopheroxy)-11-(α-tocopheroxy)-9-octadecenoates (5), a mixture of methyl 9-(α-tocopheroxy)-10,12-octadecadienoates and methyl 13-(α-tocopheroxy)-9, 11-octadecadienoates (6), α-tocopherol spirodiene dimer (7), and α-tocopherol trimer (8). α-Tocopherol and 13-MeLOOH were dissolved in methyl myristate, and the thermal decomposition rate and the distributions of reaction products formed from α-tocopherol and 13-MeLOOH were analyzed. α-Tocopherol disappeared during the first 20 min, and the main products of α-tocopherol were 5 and 6 with the accumulation of 1–4 which were the products of 13-MeLOOH. The results indicate that the alkyl and alkoxyl radicals from the thermal decomposition of 13-MeLOOH could be trapped by α-tocopherol to produce 5 and 6. The reaction products of α-tocopherol during the thermal oxidation of methyl linoleate were compounds 6 and 7. Since the radical flux during the autoxidation might be low, the excess α-tocopheroxyl radical reacted with each other to form 7.     

Synthesis and <Emphasis Type="Italic">in vitro</Emphasis> cytotoxic activity of N-, F-, and S-ether derivatives of podophyllotoxin fatty acid adducts

This paper represents the first synthesis, spectroscopic characterization, and antitumor evaluation of F-, N-, and S-containing C₄α-FA derivatives of podophyllotoxin. In a synthetic strategy, a FA unit of 4-O-podophyllotoxinyl 12-hydroxyoctadec-Z-9-enoate 2, a derivative of podophyllotoxin, was functionalized at the C−12 position by incorporating the F atom and N-containing moieties. The FA olefin (Z, C−9/C−10) of 2 was hydrogenated to produce a derivative possessing a hydroxy function (C−12) on a saturated C₁₈ FA chain. In another synthetic strategy, two S-ethers of podophyllotoxin (C₄α) were synthesized from a terminal unsaturated FA analog, 4-O-podophyllotoxinyl undec-10-enoate. Syntheses were achieved through effective synthetic procedures; ¹H NMR, ¹³C NMR, IR, and high-resolution mass data proved excellent tools to characterize these derivatives. In vitro antitumor activity was investigated against a panel of five human neoplastic cell lines, SK-MEL (malignant, melanoma), KB (epidermal carcinoma, oral), BT-549 (ductal carcinoma, breast), SK-OV-3 (ovary carcinoma), and HL-60 (human leukemia). Keeping in view the severe lack of tumor selectivity of podophyllotoxin over normal cells, we assayed new analogs against noncancerous mammalian VERO (African green monkey kidney fibroblast) cell lines to gauge their extent of toxicity. Several of these compounds showed excellent moderation of antitumor activity. In general, we found excellent growth inhibition against the human leukemia cell line (HL-60), particularly for the analogs containing S-ethers and carbamates. None of the compounds were toxic to normal cell lines.