Optical Configuration Analysis of Hydroxy Fatty Acids in Bacterial Lipids by Chiral Column High-Performance Liquid Chromatography

Through the adoption of a chiral stationary phase in high-performance liquid chromatography and a simple derivatization method for hydroxy fatty acids, it became easy to separate and identify the optical isomers of 2- and 3-hydroxy fatty acids composing several kinds of microbial lipids. The 2- and 3-hydroxy fatty acids were converted with dinitrophenyl isocyanate to their 3, 5-dinitrophenyl urethane derivatives (DU-derivatives), which were analyzable by HPLC using a chiral column. By varying the composition of an eluent, separation of the DU-derivatives of hydroxy fatty acids differing in optical configuration, chain length and position of hydroxyl group was achieved. The general elution orders of these DU-derivatives were determined with authentic 2- and 3-hydroxy fatty acids. Small amounts (~300 μg) of ornithine-containing lipids isolated from the Serratia marcescens strains were examined by this method to identify 3-hydroxy fatty acids of the lipids as D isomers.     

3-Alkyl-2-phenylbenzo[b]thiophenes: nonsteroidal estrogen antagonists with mammary tumor inhibiting activity.

A number of 2-(4-hydroxyphenyl)benzo[b]thiophenes with a hydroxy group in position 5 or 6 and a short alkyl group at C-3 were synthesized and studied for their estrogen receptor affinities. Relative binding affinities (RBA) for the calf uterine estrogen receptor ranged from 3 to 60 (17β-estradiol = 100). The highest RBA values were found with ethyl derivatives [3 (5-OH): 60; 7 (6-OH): 28]. In accord with their receptor affinity, all benzothiophenes exhibited endocrine activity in the immature mouse uterine weight test. At doses of 0.25–7.0 mg/kg body weight, they showed partial estrogen antagonism and usually weak estrogenic effects. All compounds entered tests with hormone-sensitive human MCF-7 breast cancer cells. At concentrations of 1μM and higher, most of the derivatives displayed significant inhibition of cell growth. These results prompted us to test them in vivo for cytostatic activity using hormone-dependent MXT mouse mammary tumors. The 5-hydroxy derivatives 3 and 4 strongly inhibited the growth of these tumors. After 4 weeks of treatment with 3 × 4.2 mg/kg of compound 3, the average tumor weight was reduced by 83% vs control (tamoxifen at equimolar dose: 74%). The 6-hydroxy derivative 7 required higher doses (25 mg/kg) to give rise to the same effect. At the end of therapy, no increase of uterine weight due to an estrogenic effect was observed. We assume therefore that the antineoplastic activity of these compounds in this tumor model is due mainly to their estrogen antagonism.     

Hydrolysis of lignocellulosic feedstock by novel cellulases originating from Pseudomonas sp. CL3 for fermentative hydrogen production

A newly isolated indigenous bacterium Pseudomonas sp. CL3 was able to produce novel cellulases consisting of endo-β-1,4-d-glucanase (80 and 100 kDa), exo-β-1,4-d-glucanase (55 kDa) and β-1,4-d-glucosidase (65 kDa) characterized by enzyme assay and zymography analysis. In addition, the CL3 strain also produced xylanase with a molecular weight of 20 kDa. The optimal temperature for enzyme activity was 50, 45, 45 and 55 °C for endo-β-1,4-d-glucanase, exo-β-1,4-d-glucanase, β-1,4-d-glucosidase and xylanase, respectively. All the enzymes displayed optimal activity at pH 6.0. The cellulases/xylanase could hydrolyze cellulosic materials very effectively and were thus used to hydrolyze natural agricultural waste (i.e., bagasse) for clean energy (H₂) production by Clostridiumpasteurianum CH4 using separate hydrolysis and fermentation process. The maximum hydrogen production rate and cumulative hydrogen production were 35 ml/L/h and 1420 ml/L, respectively, with a hydrogen yield of around 0.96 mol H₂/mol glucose.     

Synthesis and bioactivity studies on new 4-(3-(4-Substitutedphenyl)-3a,4-dihydro-3H-indeno[1,2-c]pyrazol-2-yl) benzenesulfonamides

A series of new 4-(3-(4-substitutedphenyl)-3a,4-dihydro-3H-indeno[1,2-c]pyrazol-2-yl) benzenesulfonamides (7–12) was synthesized starting from 2-(4-substitutedbenzylidene)-2,3-dihydro-1H-inden-1-one (1–6) and 4-hydrazinobenzenesulfonamide. The substituted benzaldehydes from which the key intermediate was prepared by introducing 2- or 4-substituents such as fluorine, hydroxy, methoxy, or the 3,4,5-trimethoxy moieties. The compounds were tested for their cytotoxicity, tumor-specificity and potential as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The 3,4,5-trimethoxy and the 4-hydroxy derivatives showed interesting cytotoxic activities, which may be crucial for further anti-tumor activity studies, whereas some of these sulfonamides strongly inhibited both human (h) cytosolic isoforms hCA I and II.     

An Anti-plasmin Inhibitor,Eckol, Isolated from the Brown Alga Ecklonia kurome Okamura

The biological activities of eckol, a novel phlorotannin with a dibenzo-β-dioxine skeleton, were examined. Eckol inhibited the antiplasmin activity of a₂-plasmin inhibitor very efficiently (IC₅₀; 1.6 μg/ml) as well as those of α₂-macroglobulin and -antitrypsin. However, its inhibitory effect on the antithrombin III-heparin complex was very weak. Eckol also showed inhibitory activity on thrombin (IC₅₀; 12 μg/ml), but not on plasmin. Its inhibitory activity was reduced in whole human plasma, but at concentrations of above 200 μg/ml it enhanced urokinase-induced fibrinolysis in human plasma. Studies on the inhibitory spectra of several derivatives of eckol showed that the dibenzo-l,4-dioxane skeleton was necessary for inhibition of plasmin inhibitor. These observations suggest that eckol or its derivatives may be useful clinically for potentiating thrombolytic activity.     

Investigation of cytochrome P450 1A2 and 3A inhibitory properties of Danshen tincture

Danshen (Salvia miltiorrhiza Bunge) as a famous Traditional Chinese medicine is widely used in the treatment of cardiovascular and cerebrovascular diseases in the world. Danshen tincture (DT), extracted from Danshen root with a mixture of water and alcohol, is a commonly used preparation method for human consumption. The aim of this study was to investigate the effects of DT on the cytochrome P450 (CYP) 1A2 and 3A activities by human and rat liver microsomes. Effects of DT were assessed with use of Danshen ethanolic extract (DEE) and selective substrates, markers of CYP activities. DEE (0.5-10 μg/ml) competitively inhibited human and rat liver microsomal CYP1A2 activity with inhibition constant (K(i)) values at 3.40 and 5.16 μg/ml, respectively. At the same time, DEE (2.5-20 μg/ml) not only noncompetitively inhibited human liver microsomal CYP3A4/5 activity with a K(i) of 11.9 μg/ml, but also competitively inhibited rat liver microsomal CYP3A1/2 activity with a K(i) of 52.1 μg/ml. The data indicate that DEE inhibited the metabolism of CYP1A2 and 3A substrates in human and rat liver in vitro with different mode of inhibition. This study may be helpful for clinical application of Danshen tincture.     

Substrate stereochemistry of the enoyl-CoA hydratase reaction.

1. A specimen of stereospecifically 2-tritiated 3-hydroxybutyric acid was prepared by hydroboration of ethyl crotonate. It was assumed that the hydroboration reaction took a syn course and hence that (2R,3S) plus (2S,3R)-3-hydroxy[2 minus 3H1]butyric acid was formed after oxidation and hydrolysis. 2. 3RS-3-Hydroxy[2 minus 3H2]butyric acid, symmetrically tritiated at C-2, was prepared by isotopic exchange of ethyl acetoacetate in tritiated water, followed by reduction and hydrolysis. 3. The 3R-enantiomers of the acids listed under paragraphs (1) and (2) were destroyed enzymically by use of 3R-specific 3-hydroxybutyrate dehydrogenase and the residual 3S-enantiomers were isolated. 4. The resulting specimens of 2R,3S-3-hydroxy[2 minus 3H1]butyric acid and 3S-3hydroxy[2 minus 3H2]-butyric acid were converted chemically to the acyl-CoA derivatives. These were incubated with enoyl-CoA hydratase. 5. In the presence of the enoyl-CoA hydratase symmetrically labelled 3S-3-hydroxy[2 minus 3H2]BUTYRYL-CoA lost nearly 50% of its tritium label; 2R,3S-3hydroxy [2-3-H1]butyryl-CoA lost about 78%. 6. It was concluded that the elimination of the elements of water from 3-hydroxybutyryl-CoA on the hydratase occurs stereospecifically with syn geometry.     

Rifamycin derivatives: specific inhibitors of nucleic acid polymerases

Rifampicin and three rifamycin SV derivatives with different lipophilic side chains were tested as inhibitors of a number of purified enzymes including the α and αβ forms of RNA-directed DNA polymerase of avian myeloblastosis virus (AMV). $\text{AF}\text{ABDMP}$ (2,5-dimethyl-4-N-benzyl demethyl rifampicin), $\text{AF}\text{013}$ (O-n-octyloxime of 3-formyl rifamycin SV) and C-27 (rifamycin SV with a dicyclohexylalkyl substituted piperidyl ring at the 3-position) at concentrations less than 20 to 40 μg/ml completely inhibited the RNA- and DNA-directed DNA polymerase and RNase H activities of both AMV enzymes. Rifampicin was inactive at 100 μg/ml. When used against a variety of non-polymerizing enzymes such as alkaline phosphatase, glutamate-oxaloacetate transaminase, DNase I, and RNase A, these derivatives were inactive at drug concentrations between 100 and 200 μg/ml. Polynucleotide phosphorylase was inhibited slightly by all three derivatives. These results support the idea that rifamycin SV derivatives with appropriate 3-substituted side-chains are specific inhibitors of nucleic acid polymerizing enzymes.     

3-Alkyl-2-phenylbenzo[b]thiophenes: Nonsteroidal estrogen antagonists with mammary tumor inhibiting activity

A number of 2-(4-hydroxyphenyl)benzo[b]thiophenes with a hydroxy group in position 5 or 6 and a short alkyl group at C-3 were synthesized and studied for their estrogen receptor affinities. Relative binding affinities (RBA) for the calf uterine estrogen receptor ranged from 3 to 60 (17β-estradiol = 100). The highest RBA values were found with ethyl derivatives [3 (5-OH): 60; 7 (6-OH): 28]. In accord with their receptor affinity, all benzothiophenes exhibited endocrine activity in the immature mouse uterine weight test. At doses of 0.25–7.0 mg/kg body weight, they showed partial estrogen antagonism and usually weak estrogenic effects. All compounds entered tests with hormone-sensitive human MCF-7 breast cancer cells. At concentrations of 1μM and higher, most of the derivatives displayed significant inhibition of cell growth. These results prompted us to test them in vivo for cytostatic activity using hormone-dependent MXT mouse mammary tumors. The 5-hydroxy derivatives 3 and 4 strongly inhibited the growth of these tumors. After 4 weeks of treatment with 3 × 4.2 mg/kg of compound 3, the average tumor weight was reduced by 83% vs control (tamoxifen at equimolar dose: 74%). The 6-hydroxy derivative 7 required higher doses (25 mg/kg) to give rise to the same effect. At the end of therapy, no increase of uterine weight due to an estrogenic effect was observed. We assume therefore that the antineoplastic activity of these compounds in this tumor model is due mainly to their estrogen antagonism.     

Discovery of novel 5-(ethyl or hydroxymethyl) analogs of 2'-'up' fluoro (or hydroxyl) pyrimidine nucleosides as a new class of Mycobacterium tuberculosis, Mycobacterium bovis and Mycobacterium avium inhibitors

Discovery of novel antimycobacterial compounds that work on distinctive targets and by diverse mechanisms of action is urgently required for the treatment of mycobacterial infections due to the emerging global health threat of tuberculosis. We have identified a new class of 5-ethyl or hydroxy (or methoxy) methyl-substituted pyrimidine nucleosides as potent inhibitors of Mycobacterium bovis, Mycobacterium tuberculosis (H37Ra, H37Rv) and Mycobacterium avium. A series of 2'-'up' fluoro (or hydroxy) nucleosides (1, 2, 4-6, 9, 10, 13, 16, 18, 21, 24) was synthesized and evaluated for antimycobacterial activity. Among 2'-fluorinated compounds, 1-(3-bromo-2,3-dideoxy-2-fluoro-β-d-arabinofuranosyl)-5-ethyluracil (13) exhibited promising activity against M. bovis and Mtb alone, and showed synergism when combined with isoniazid. The most active compound emerging from these studies, 1-(β-d-arabinofuranosyl)-4-thio-5-hydroxymethyluracil (21) inhibited Mtb (H37Ra) (MIC(50)=0.5 μg/mL) and M. bovis (MIC(50)=0.5 μg/mL) at low concentrations, and was ten times more potent against Mtb (H37Ra) than cycloserine (MIC(50)=5.0 μg/mL), a second line drug. It also showed an additive effect when combined with isoniazid. Compound 21 retained sensitivity against a rifampicin-resistant (H37Rv) strain of Mtb (MIC(50)=1 μg/mL) at concentrations similar to that for a rifampicin-sensitive (H37Rv) strain, suggesting that it has no cross-resistance to a first-line anti-TB drug. In addition, the replication of M. avium was also inhibited by 21 (MIC(50)=10 μg/mL). No cellular toxicity of 13 or 21 was observed up to the highest concentration tested (CC(50)>100 μg/mL). These observations offer promise for a new drug treatment regimen to augment and complement the current chemotherapy of TB.     

Effects of plumbagin on development of the parasitic nematodes Haemonchus contortus and Ascaris suum

1. Plumbagin (5-hydroxy,2-methyl-l,4-napthoquinone) inhibited the motility and survival of Haemonchus contonus first-stage larvae (L1) with an ed₅₀ of 1 μg/ml, but was less effective in preventing the development of H. contortus to infective third-stage larvae in a faecal slurry assay.2. Of the structural analogs tested, plumbagin was the most potent in preventing development of L1 followed in decreasing order of potency by 1,4-napthoquinone, 5-hydroxy-1,4-napthoquinone (juglone) and 1,2-napthoquinone.3. Plumbagin had a biphasic effect on development of the fourth-stage Ascaris suum larvae that caused an increase in growth at low concentrations but was lethal at higher doses.4. Plumbagin and 1,2-napthoquinone partially inhibited embryonation of A. suum eggs.     

Molecular docking analysis of selected pyrimidine derivatives with human cyclin-dependent kinase 2

A series of pyrimidine were synthesized, characterized and evaluated for their antioxidant properties using the human cyclin-dependent kinase-2 protein model. Data shows that the pyrimidine derivatives (compound ID 4G) with para fluoro groups substitution at phenyl ring attached to the 4th position (IC50: 98.5µg/ml), compound 4B bearing hydroxy group at para position of phenyl ring (IC50: 117.8 µg/ml) have significant antioxidant activity. Docking data infer that compounds 4c, 4a, 4h and 4b possess binding energy (-7.9, -7.7, -7.5 and -7.4 kcal.mol-1) with 1HCK (PDB ID) receptor.     

Studies on platelet lipoxygenase specificity towards icosapolyenoic and docosapolyenoic acids

Two docosapolyenoic acids (22:5(n-3) and 22:5(n-6)) were isolated from the liver of normal and 18:3(n-3)-deficient trout, respectively. They were prepared by combined thin-layer chromatography (TLC) and reversed-phase high performance liquid chromatography (HPLC). Their purity, checked by capillary gas liquid chromatography, was greater than 95%. Each fatty acid was oxygenated into monohydroxy derivatives by human platelets. The hydroxy compounds were purified by TLC and HPLC and then derivatized for gas chromatography-mass spectrometry analysis. Whereas 22:5(n-6) was only converted into 14-OH-22:5, three hydroxy derivatives (11, 13 and 14) were obtained from 22:5(n-3). However, 13-hydroxy was not formed in the presence of aspirin, indicating that platelet lipoxygenase catalyses the formation of both 11- and 14-hydroxy derivatives from 22:5(n-3), as described previously, from 22:6(n-3). Further studies showed that 22:4(n-6) and 20:5(n-3) were only converted into 14- and 12-hydroxy derivatives. We conclude then that, besides the well-known n-9 oxygenation, lipoxygenase of human platelets is able to catalyse an n-12 oxygenation on docosapolyenoic acids of the n-3 family.     

Effects of safrole and isosafrole pretreatment on N- and ring-hydroxylation of 2-acetamidofluorene by the rat and hamster

1. The effects of safrole and isosafrole pretreatment on both N- and ring-hydroxylation of 2-acetamidofluorene were studied in male rats and hamsters. 2. Isosafrole (100mg/day per kg body wt.) pretreatment of rats for 3 days did not have any effect on urinary excretion of hydroxy metabolites of 2-acetamidofluorene. However, similar pretreatment with safrole produced increased urinary excretion of N-, 3- and 5-hydroxy derivatives. 3. Similar treatment with these two chemicals for 3 days increased ring-hydroxylation activity by rat liver microsomal material. Increases in N-hydroxylation were much less than those in ring-hydroxylation. Isosafrole was twice as effective as safrole. 4. Increases in hydroxylating activity due to safrole or isosafrole treatment were inhibited by simultaneous administration of ethionine. Similarly, ethionine inhibition was almost completely reversed by the simultaneous administration of methionine. 5. Safrole or isosafrole (0.1mm and 1mm) inhibited 7-hydroxylation activity by liver microsomal material from control rats. At 1mm these two chemicals inhibited both 5- and 7-hydroxylation activity by liver microsomal material from 3-methylcholanthrene-pretreated rats. 3-Hydroxylation activity was not inhibited by 1mm concentrations of these two chemicals. 6. A single injection of safrole (50100 or 200mg/kg body wt.) 24h before assay had no appreciable effect on either N- or ring-hydroxylation activity by hamster liver microsomal material. However, isosafrole (200mg/kg body wt.) treatment inhibited N-, 3- and 5-hydroxylation activities by hamster liver microsomal material; it had no effect on 7-hydroxylation activity.     

Study of hyaluronan synthase inhibitor, 4-methylumbelliferone derivatives on human pancreatic cancer cell (KP1-NL)

The structure of 4-methylumbelliferone (MU) consists of coumarin with 4-methyl group and 7-hydroxy group. MU inhibits HA synthesis and pericellular HA matrix formation. In this study, we used 10 MU derivatives which have hydroxy groups and methyl groups at various positions of coumarin to investigate a more effective HA inhibitor than MU. First, human pancreatic cancer cell (KP1-NL) growth assay was analyzed by Alamar Blue to determine the non-toxic concentration of MU derivatives, and the inhibitory effect on HA synthesis in the cell cultures was analyzed by HA measuring kit. Next, cell surfaces of cancer cells were analyzed by particle-exclusion assay. In conclusion, both hydroxy and methyl groups are necessary for HA inhibition by MU, and two hydroxy groups inhibited HA synthesis more strongly than MU.     

The platelet-activating factor receptor antagonist L-659,989 inhibits phospholipase D activity

The platelet-activating factor (PAF) receptor antagonist L-659,989 [(±)-trans-2-(3-methoxy-5-methylsulfonyl-4-propoxyphenyl)-5-(3,4,5-trimethoxyphenyl)tetrahydrofuran)] has been reported to be a specific inhibitor of the PAF receptor and as such, it is widely used for assessment of PAF receptor mediated biological effects. We report here that L-659,989 may not be as specific as previously reported because it is also a potent inhibitor of phospholipase D activity. At concentrations of 30 μg/ml, L-659,989 inhibited basal and agonist-stimulated phospholipase D activity by about 55% and 70–100% respectively, through a mechanism that may involve the generation of intracellular ceramides. Another PAF receptor antagonist, WEB-2086, did not affect phospholipase D activity at concentrations up to 50 μg/ml. Either of these inhibitors when present at 20 μg/ml are reported to fully block the effects of PAF. Furthermore, L-659,989 directly inhibited the activity of bacterial PLD in vitro. These results indicate that caution is required in the interpretation of results derived from the use of L-659,989.     

Peptides with antimicrobial and anti-inflammatory activities that have therapeutic potential for treatment of acne vulgaris

The pathogenesis of acne vulgaris is multifactorial involving infection of the pilosebaceous unit with Propionibacterium acnes and a cytokine-mediated inflammatory response. Five frog skin-derived antimicrobial peptides ([D4k]ascaphin-8, [G4K]XT-7, [T5k]temporin-DRa, brevinin-2GU, and B2RP-ERa), chosen for their low hemolytic activity against human erythrocytes, were assessed for their effects on the growth of clinical isolates of P. acnes and on the release of pro-inflammatory and anti-inflammatory cytokines from peripheral blood mononuclear (PBM) cells. All peptides inhibited the growth of P. acnes with the highest potency exhibited by [D4k]ascaphin-8 (minimum inhibitory concentration, MIC=3-12.5 μM). Release of TNF-α from concanavalin A (ConA)-stimulated PBM cells was significantly reduced by [D4k]ascaphin-8, [G4K]XT-7, brevinin-2GU, and B2RP-ERa (1 and 20 μg/ml) and by [T5k]temporin-DRa (20 μg/ml). Release of IFN-γ from unstimulated PBM cells was significantly reduced by [D4k]ascaphin-8 and brevinin-2GU (1 and 20 μg/ml). No peptide showed significant effects on Il-17 release. Release of the anti-inflammatory cytokines TGF-β, IL-4, and IL-10 from both unstimulated and ConA-treated PBM cells was significantly increased by [T5k]temporin-DRa and B2RP-ERa (1 and 20μg/ml). The potent activities of [D4k]ascaphin-8 and [T5k]temporin-DRa in inhibiting the growth of P. acnes and the release of pro-inflammatory cytokines, and in stimulating the release of anti-inflammatory cytokines suggest a possible therapeutic role in the treatment of acne vulgaris.     

Synthesis and Inhibitory Activity Against Phosphatidylinositol 4-Kinase of Echiguanine Analogs

Abstract

N-Substituted-2-amino-4(3H)-7H-oxopyrrolo[2,3-d]pyrimidine-5-carboxamides and their ribofuranosyl and 2′,3′-dideoxyribofuranosyl derivatives were prepared as membrane permeable echiguanine analogs and tested for their ability to inhibit phosphatidylinositol (PI) 4-kinase. The ethylamide 5 and the corresponding ribofuranosyl compound 11 inhibited PI 4-kinase with IC₅₀ values of 0.02 and 2.4 μg/ml, respectively.     

Action of two juvenile hormone antagonists on lepidopteran epidermis

The juvenile hormone antagonist ETB (ethyl-4-2(t-butylcarbonyloxy)-butoxybenzoate) caused formation of precocious larval-pupal intermediates after the 4th (penultimate)-larval instar of the tobacco hornworm, Manduca sexta, when 50 μg were applied to any 3rd stage larvae or to 4th stage larvae within 12 hr after ecdysis. This dose was most effective within 12 hr after ecdysis to the 3rd stage. In the black mutant larval assay for juvenile hormone, ETB had activity, 0.75 μg per larva giving half-maximal score. In vitro ETB acted as a juvenile hormone to prevent the ecdysteroid-induced change in commitment at concentrations above 0.1 μg/ml with an ED₅₀ at 2.8 μg/ml and as a partial juvenile hormone antagonist to 0.1 μg/ml juvenile hormone I at concentrations between 10^?3 and 10^?2 μg/ml. By contrast, EMD (ethyl-E-3-methyl-2-dodecenoate) had little juvenile hormone-like activity in vitro up to its limits of solubility (100 μg/ml) and exhibited sporadic partial juvenile hormone antagonistic activity in vitro at concentrations between 1 and 100 μg/ml. Since these concentrations were 10–1000 times that of juvenile hormone I in the medium, EMD apparently is not an efficient competitor.     

Antimicrobial and Cytotoxic Activity of Extracts of Ferula heuffelii Griseb. ex Heuff. and Its Metabolites

The antimicrobial and cytotoxic activities of isolates (CHCl₃ and MeOH extracts and selected metabolites) obtained from the underground parts of the Balkan endemic plant Ferula heuffelii Griseb . ex Heuff . were assessed. The CHCl₃ and MeOH extracts exhibited moderate antimicrobial activity, being more pronounced against Gram‐positive than Gram‐negative bacteria, especially against Staphylococcus aureus (MIC=12.5 μg/ml for both extracts) and Micrococcus luteus (MIC=50 and 12.5 μg/ml, resp.). Among the tested metabolites, (6E)‐1‐(2,4‐dihydroxyphenyl)‐3,7,11‐trimethyl‐3‐vinyldodeca‐6,10‐dien‐1‐one ( 2 ) and (2S*,3R*)‐2‐[(3E)‐4,8‐dimethylnona‐3,7‐dien‐1‐yl]‐2,3‐dihydro‐7‐hydroxy‐2,3‐dimethylfuro[3,2‐c]coumarin ( 4 ) demonstrated the best antimicrobial activity. Compounds 2 and 4 both strongly inhibited the growth of M. luteus (MIC=11.2 and 5.2 μM , resp.) and Staphylococcus epidermidis (MIC=22.5 and 10.5 μM , resp.) and compound 2 additionally also the growth of Bacillus subtilis (MIC=11.2 μM ). The cytotoxic activity of the isolates was tested against three human cancer cell lines, viz., cervical adenocarcinoma (HeLa), chronic myelogenous leukemia (K562), and breast cancer (MCF‐7) cells. The CHCl₃ extract exhibited strong cytotoxic activity against all cell lines (IC₅₀<11.0 μg/ml). All compounds strongly inhibited the growth of the K562 and HeLa cell lines. Compound 4 exhibited also a strong activity against the MCF‐7 cell line, comparable to that of cisplatin (IC₅₀=22.32±1.32 vs. 18.67±0.75μM ).