Synthesis and in vitro antiplasmodial activity of quinoline-ferrocene esters

New 4-aminoquinoline-derived esters containing the redox-active ferrocene group brought in by either ferrocenyformic or 4-ferrocenylbutanoic acids were synthesized and tested in vitro for their antiplasmodial activity. The results revealed that only esters derived from ferrocenylformic acid were active against both chloroquine (CQ)-resistant Dd2 and CQ-sensitive D10 strains of Plasmodium falciparum. However, none of these showed higher actvity than CQ against the sensitive strain. Ester 16, which possesses a butyl branch in the structure, was the most active of all. With an IC50 of 0.13 mM on the resistant strain, this ester possessed 2.5-fold higher activity than CQ (IC50 = 0.34 mM). All tested esters showed good selectivity towards P. falciparum with indexes higher than 60.     

The novel L- and D-amino acid derivatives of hydroxyurea and hydantoins: synthesis, X-ray crystal structure study, and cytostatic and antiviral activity evaluations

The novel L- and D-amino acid derivatives of hydroxyurea 5a-o were prepared by aminolysis of N-(1-benzotriazolecarbonyl)amino acid amides 4a-o with hydroxylamine. The hydantoin derivatives 6a-e,m,p were synthesized by base-catalyzed cyclization of amides 4, common precursors for 5 and 6. X-ray crystal structure analysis shows that the C5 atom in 6e possesses the S configuration, which is consistent with the configuration of the starting reagent, l-leucine. Among L-amino acid derivatives of hydroxyurea, 5h and 5i inhibited specifically murine leukemia and human T-lymphocytes (IC(50) = 10-19 microM) and showed selectivity with respect to normal human fibroblasts (WI 38). d-Amino acid derivatives of hydroxyurea 5m and 5o inhibited the growth of all tumor cell lines (IC(50) = 4.8-83.9 microM), but not the growth of normal fibroblasts (WI 38; IC(50) > 100 microM). Results on antiviral evaluations showed that N-(1-benzotriazolecarbonyl)amino acid amide 4m and hydantoin 6m had marked activity against the Davis strain of CMV (4m, EC(50) = 3.2 microg/mL; 6m, EC(50) = 4.0 microg/mL). However, these compounds showed also rather expressed cytotoxicity (4m, CC(50) = 43.4 microg/mL; 6m, CC(50) = 12.5 microg/mL(-1)).     

Synthesis, X-ray crystal structure study, and cytostatic and antiviral evaluation of the novel cycloalkyl-N-aryl-hydroxamic acids

In vitro evaluation of the novel cycloalkyl-N-(4-chlorophenyl)-hydroxamic acids (2a-g) demonstrated that 2b,d,e exhibited rather marked inhibitory activity (IC50 = 7-10 microM) against pancreatic carcinoma, 2b-d against colon carcinoma, 2d against laryngeal carcinoma, and 2b,d against breast carcinoma. 2e showed the most pronounced anti-cytomegalovirus activity (EC50 = 1.5 and 0.8 microg mL(-1)) only at > or = 5-fold lower than the cytotoxic concentration. 2d and 2f showed modest, albeit selective, activity against cytomegalovirus (2d, EC50 = 7.3-8.9 microg mL(-1), selectivity index 7-10; 2f, EC50 = 7-13 microg mL(-1), selectivity index 10).     

Jacaranone: A cytotoxic constituent from<Emphasis Type="Italic">senecio ambiguus</Emphasis> subsp.<Emphasis Type="Italic">ambiguus</Emphasis> (Biv.) DC. Against renal adenocarcinoma achn and prostate carcinoma LNCaP cells

Senecio ambiguus subsp. ambiguus (Biv.) DC. extracts were able to inhibit the in vitro proliferation of renal cell adenocarcinoma ACHN and hormone dependent prostate carcinoma LNCaP. The potential cytotoxic property of the plant was revealed by the methanolic extract action against LNCaP (IC50 of 5.51 microg/mL) and ACHN (IC50 of 38.95 microg/mL). The most potent cytotoxic activity (IC50 of 5.34 microg/mL against the prostate carcinoma cell line) was exerted by the dichloromethane extract. Through bioassay-guided fractionation of the dichloromethane extract jacaranone was isolated as the major active constituent. This quinoid showed a very strong activity against ACHN and LNcaP with IC50 of 4.32 and 7.39 microg/mL, respectively. Its structure was established by GC/MS and NMR analysis. The n-hexane extract showed an interesting inhibition on the proliferation of tumor cell lines an IC50 value of 5.23 microg/mL against LNCaP. Three compounds identified in the n-hexane extract such as nerolidol, a-humulene and g-tocopherol were found to be active aginst LNCAP with IC50 values ranged from 11.24 to 15.56 microg/mL.     

Antiamoebic activity of iridoids from Morinda morindoides leaves

An aqueous decoction (dried extract), an 80 % methanolic extract from Morinda morindoides (Rubiaceae) leaves, and five iridoids isolated from the 80 % methanolic extract were evaluated in vitro for their activity against Entamoeba histolytica and their cytotoxicity. The aqueous decoction and the 80 % methanolic extract exhibited a promising antiamoebic activity with IC (50) values of 3.1 +/- 1.7 and 1.7 +/- 0.6 microg/mL, respectively. All tested iridoids displayed antiamoebic activity, the most active being epoxygaertneroside (IC (50): 1.3 +/- 0.4 microg/mL) and methoxygaertneroside (IC (50): 2.3 +/- 0.7 microg/mL) followed by gaertneroside, acetylgaertneroside and gaertneric acid with IC (50) values of 4.3 +/- 1.8, 5.4 +/- 1.4 and 7.1 +/- 1.4 microg/mL, respectively. Synergistic effects between the iridoids tested, or with other constituents, may explain the high activity of the extracts. All extracts and iridoids were devoid of any cytotoxic effect against MT-4 cells at the highest test concentration of 250 microg/mL. These findings support at least in part the traditional use of Morinda morindoides leaves for the treatment of amoebiasis in the Democratic Republic of Congo.     

Biological Activities of the Chemical Constituents of<Emphasis Type="Italic">Erythrina stricta</Emphasis> and<Emphasis Type="Italic">Erythrina subumbrans</Emphasis>

Phytochemical investigation of the hexane and CH2Cl2 extracts of Erythrina stricta roots and E. subumbrans stems led to the isolation of six pterocarpans, one flavanone, one isoflavone, two alkaloids, five triterpenes, six steroids and alkyl trans-ferulates. The structures of all known compounds were determined on the basis of spectroscopic evidence. Sophoradiol (15), a mixture of stigmast-4-en-3-one (19) and stigmasta-4,22-dien-3-one (20), lupeol (21), cycloeucalenol (22), a mixture of 3beta-hydroxystigmast-5-en-7-one (23) and 3beta-hydroxystigmast-5,22-dien-7-one (24) and melilotigenin C (25) were first isolated from the genus Erythrina. The isolated compounds were evaluated for antiplasmodial activity, antimycobacterial activity and cytotoxicity. Among the tested compounds, 5-hydroxysophoranone (8) exhibited the highest antiplasmodial activity against Plasmodium falciparum (IC50 2.5 microg/mL). Compound 8, erystagallin A (5), erycristagallin (7) and erysubin F (10) showed the same level of antimycobacterial activity against Mycobacterium tuberculosis (MIC 12.5 microg/mL). For cytotoxicity, erybraedin A (2) showed the highest activity against the NCI-H187 and BC cells (IC50 2.1 and 2.9 microg/mL, respectively), whereas 10 exhibited the highest activity against the KB cells (IC50 4.5 microg/mL).     

Two new abietane diterpenoids from Salvia yunnanensis

Two new abietane diterpenoids, yunnannin A and danshenol C, were isolated from Salvia yunnanensis together with ten known diterpenoids, danshenol A, przewalskin, tanshinone IIA, tanshinone I, crypotanshinone, 1,2-dihydrotanshinone, tanshinlactone, 5,6-dehydrosugiol, 12-hydroxy-6,7-seco-8,11,3-abietatriene-6,7-dial and phytol. Their structures were established based on spectroscopic data, chemical reactions and comparison with literature data. Compounds were tested for their antitumor activity in T-24, QGY, K562, Me180 and BIU87 cell lines. Compound showed inhibited growth of K562 (IC50=0.53 microg/mL), T-24 (IC50=7.94 microg/mL), QGY (IC50=4.65 microg/mL) and Me180 (IC50=6.89 microg/mL) cell lines while compound was inactive. Compound showed moderate inhibitory activity on QGY (IC50=16.75 microg/mL) and Me180 (IC50=5.84 microg/mL) cells.     

In-vitro antiproliferative effects on human tumour cell lines of extracts and jacaranone from Senecio leucanthemifolius Poiret

We have studied the cytotoxic activity of extracts and jacaranone from Senecio leucanthemifolius Poiret. Extracts from S. leucanthemifolius were able to inhibit the in-vitro proliferation of a series of human tumour cell lines. The dichloromethane extract demonstrated effective cytotoxic activity with an IC50 of 20.1 microg mL(-1) on the large cell carcinoma cell line COR-L23. The ethyl acetate extract showed an IC50 value of 5.0 microg mL(-1) and the butanol extract an IC50 value of 6.4 microg mL(-1) on the same cell line. A major active constituent of the dichloromethane extract was shown to be jacaranone, which was demonstrated to have a very strong activity against all of the tumour cell lines with IC50 values between 2.86 and 3.85 microg mL(-1), although it did not account for all the activity observed. Constituents of S. leucanthemifolius extracts were identified by GC/MS analysis and NMR.     

Three new asterosaponins from the starfish Culcita novaeguineae and their bioactivity

Bioassay-guided fractionation of the active n-BuOH extract of the starfish Culcita novaeguineae resulted in the isolation of three new sulfated steroidal glycosides (asterosaponins) 1, 2 and 3, as active compounds causing morphological abnormality of Pyricularia oryzae mycelia. Compounds 1-3 possess the same pentasaccharide moiety, beta-D-fucopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-(1-->4)-[beta-D-quinovopyranosyl-(1-->2)]-beta-D-xylopyranosyl-(1-->3)-beta-D-quinovopyranosyl, linked to C-6 of 3beta-sulfated steroidal aglycones and differ from each other in the side chains. Their structures were elucidated by extensive spectral studies and chemical evidences. Saponins 1 and 3 showed significant cytotoxicity against two cancer cell lines (IC50 values for 1:3.57 microg/mL [K-562], 2.55 microg/mL [BEL-7402]; for 3:3.75 microg/mL [K-562], 1.89 microg/mL [BEL-7402]), as well as hemolytic activity to rabbit erythrocytes (ED50 values: 16 and 31 microg/mL, respectively), while 2 was inactive in these bioassays.     

Antiproliferative, antioxidant, and antimutagenic activities of flavonoid-enriched extracts from (Tunisian) Rhamnus alaternus L.: combination with the phytochemical composition

A pronounced antiproliferative effect on human leukemia K562 cells was shown with flavonoid-enriched extracts from Rhamnus alaternus roots and leaves, with, respectively, IC(50) values of 165 and 210.73 microg/mL. High DPPH radical-scavenging activity (7.21 and 18.84 microg/mL, respectively) and antioxidative effects using the xanthine oxidase assay (IC(50) values of 83.33 and 103.96 microg/mL, respectively) were detected in the presence of the two tested extracts. Although no mutagenic effect was observed when using the Salmonella typhimurium assay system with TA1535 and TA100 strains, the two tested extracts exhibited a high-level protection toward the direct mutagen, sodium azide-induced response.     

Synthesis and antimalarial activity of new isotebuquine analogues

Amodiaquine (AQ) and tebuquine are 4-aminoquinoline antimalarials with Mannich base side chain and are highly effective against chloroquine (CQ)-resistant strains of Plasmodium falciparum. Clinical use of AQ has been severely restricted due to hepatoxicity and agranulocytosis side effects associated with its long term use. Lysosomal accumulation and bioactivation to generate reactive quinoneimine metabolite are implicated to be the cause of the observed AQ toxicities. To avoid the quinoneimine formation and thus the toxicity, a series of isotebuquine analogues and their Nomega-oxides with hydroxy group meta to the amino rather than in para position of the aniline moiety were prepared. The new Mannich bases are highly active against both CQ-sensitive (D6) and -resistant (W2 and TM91C235) clones of P. falciparum with IC50 in the range of 0.3-120 ng/mL. New compounds are1000-fold less toxic (IC50 = 0.7-6 microg/mL) to mouse macrophage cell line than to parasite cell lines. Mono-Mannich bases are more active than bis-Mannich bases. Mono-Mannich base 1a (IC50 = 0.3 ng/mL) is 20-fold more active than the corresponding trifluoromethyl analogue 1b. No appreciable difference in either toxicity or efficacy were observed between the new Mannich bases (m-hydroxyaniline derivatives) 1a or 2a and the corresponding p-hydroxyaniline derivatives.     

Synthesis and in vitro-anticancer and antimicrobial evaluation of some novel quinoxalines derived from 3-phenylquinoxaline-2(1H)-thione

Two novel series derived from 3-phenylquinoxaline-2(1H)-thione 2 and 2-(hydrazinocarbonylmethylthio)-3-phenylquinoxaline 6 have been synthesized. Eight out of twenty six new compounds were selected at the National Cancer Institute for evaluation of their in vitro-anticancer activity. Among them, compounds 3b, 3c, 4b, and 4c displayed moderate to strong growth inhibition activity against most of the tested sub-panel tumor cell lines with GI(50) 10(-5) to 10(-6 )molar concentrations. Compound 4b exhibited a significant value of percent tumor growth inhibition against breast cancer at concentration < 10(-8) M. Compound 4c showed moderate selectivity towards leukemia cell lines with GI(50) of 1.8 to 3.8 microM (selectivity ratio = 5.7). Preliminary antimicrobial testing revealed that compounds 7a, 7b, 8a, 11a, and 11b were as active as ampicillin against B. subtilis (MIC = 12.5 microg/mL). Compounds 7b and 8a were also nearly as active as ampicillin against E. coli (MIC = 12.5 microg/mL). In addition, compounds 4a, 7b, 10b, and 11a were as active as ampicillin against P. aerugenosa (MIC = 50 microg/mL). However, compounds 7b, 8a, and 10b showed mild activity against C. albicans (MIC = 50 microg/mL). The values of minimum bactericidal concentrations indicated that compounds 4a and 7b were bactericidal against B. subtilis and P. aerugenosa, respectively, while compound 10b was bactericidal against both organisms. However, compound 11a was bactericidal against E. coli, P. aerugenosa, and S. aureus.     

Antiplasmodial activity of lignans and extracts from Pycnanthus angolensis

The dichloromethane, methanol and aqueous ethanol extracts of the stem bark of Pycnanthus angolensis were evaluated for their in vitro activity against the 3D7 Plasmodium falciparum strain. The CH (2)Cl (2) extract was the most active showing an IC (50) = 1.6 microg/mL. From this extract, a new dibenzylbutane lignan, threo-4,4'-dihydroxy-3-methoxylignan ( 1) named pycnantolol, together with the known lignans (-)-dihydroguaiaretic acid ( 2), heliobuphthalmin ( 3), talaumidin ( 4), hinokinin ( 5), the labdane-type diterpene ozic acid ( 6), and the steroids stigmast-4-en-6beta-ol-3-one ( 7), beta-sitosterol ( 8) and stigmasterol ( 9) were isolated. Their structures were established on the basis of physical and spectroscopic methods, including 2 D NMR experiments (COSY, HMQC, HMBC and NOESY). The antimalarial activity of compounds 1 - 7 was evaluated against 3D7 and Dd2 P. falciparum strains. Despite the significant activity displayed by the crude CH (2)Cl (2) extract, the isolated compounds showed weaker antiplasmodial activity. The lowest IC (50) value was obtained for talaumidin ( 4) (IC (50) = 20.7 microg/mL against the Dd2-chloroquine resistant P. falciparum strain).     

Platelet aggregation and anti-inflammatory effects of garden pea, Desi chickpea and Kabuli chickpea

Inflammation is the natural body defense mechanism for the removal of injurious agents, necrosed cells and tissues from the body. This study was aimed to evaluate the anti-inflammatory and platelet aggregation effects of three medicinal plants of Pakistan. Methanolic extract of garden pea inhibited arachidonic acid (AA)-induced platelet aggregation (IC50 = 35 microg/mL) and platelet activating factor (PAF)-induced platelet aggregation (IC50 = 38 microg/mL) in a dose dependent fashion. Methanolic extract of Desi chickpea inhibited arachidonic acid (AA) induced platelet aggregation (IC50 value = AA = 46 microg/mL) in dose dependent fashion while was found not active against PAF-induced platelet aggregation. Methanolic extract of Kabuli chickpea was found not active against both arachidonic acid (AA)-induced platelet aggregation and PAF-induced platelet aggregation. The best potential to inhibit in vitro COX-2 activity showed garden pea (Pisum sativum: the synthesis of PGE2 reduced by 92% in comparison with untreated control wells) followed by Desi chickpea (Cicer arietinum var; 87% inhibition) and Kabuli chickpea extracts (Cicer arietinum var: 65% inhibition). All extracts were tested at concentration 20 microg/mL. in COX-2 assay. The results indicate that if the same were happening in vito, Garden pea, Desi chickpea and Kabuli chickpea could be useful as natural antithrombotic anti-inflammatory materials.     

Mycological and electron microscopic study of Solanum chrysotrichum saponin SC-2 antifungal activity on Candida species of medical significance

Solanum chrysotrichum is utilized in traditional Mexican medicine for the treatment of mycotic skin infections. Several microbiological studies have provided evidence of its antifungal activity against dermatophytes and yeasts. S. chrysotrichum saponins have been identified as a group of compounds with antifungal activity and saponin SC-2 has demonstrated to be the most active. Previous clinical studies have shown the therapeutic effectiveness of S. chrysotrichum-derived saponin-standardized herbal products in the treatment of Tinea pedis and Pityriasis capitis. There is no previous evidence of the activity of these saponins against Candida non-albicans species, or fluconazole- and ketoconazole-resistant Candida strains. The present study reports the biological activity of the SC-2 saponin (inhibitory concentration [IC (50)] and minimum fungicide concentration [MFC]), against 12 Candida strains of clinical significance ( C. albicans, five strains; C. glabrata and C. parapsilosis, two; C. krusei, C. lusitaniae and C. tropicalis, one), including some fluconazole (Fluco)- and ketoconazole (Keto)-resistant clinical isolates. In addition, SC-2-associated microstructural alterations were reported in four of the above-mentioned Candida species. Seven strains had IC (50) of 200 microg/mL for SC-2, 400 microg/mL was found in four strains, and 800 microg/mL for a sole C. glabrata strain. Susceptibility to SC-2 saponin was as follows: C. albicans = C. lusitaniae > C. krusei > C. glabrata. The MFC was 800 microg/mL for the majority of strains (nine), 400 microg/mL for C. albicans (two strains) and C. lusitaniae. The ultrastructural Candida changes originated by SC-2 included the following: 1) damage on cytoplasmic membrane and organelles; 2) changes in cell wall morphology and density, with separation of cytoplasmatic membrane from cell wall and disintegration of the latter; and 3) total degradation of cellular components and death. Changes were manifested from 6 h of incubation, reaching their maximum effect at 48 h. In conclusion, the saponin SC-2 possesses fungicide and fungistatic activity on different Candida albicans and non- albicans species (including some azole-resistant strains) with IC (50) values of 200 microg/mL (in Fluco-susceptible strains) and of 400 - 800 mug/mL (in Fluco-resistant strains). Additionally, we observed by transmission electron microscopy (TEM) that saponin SC-2 causes severe changes in all fungal cell membranes, and to a lesser degree on the cell wall.     

Synthesis and in vitro studies of novel pyrimidinyl peptidomimetics as potential antimalarial therapeutic agents

A class of new pyrimidinyl peptidomimetic agents (compounds 1-6) were synthesized, and their in vitro antimalarial activities against Plasmodium falciparum were evaluated. The core structure of the new agents consists of a substituted 5-aminopyrimidone ring and a Michael acceptor side chain methyl 2-hydroxymethyl-but-2-enoate. The synthesis of 1-6 featured a Baylis-Hillman reaction of various aldehydes with methyl acrylate catalyzed by 1,4-diazabicyclo[2.2.2]octane (DABCO) and a S(N)2' Mitsunobu reaction under the conditions of diethyl azadicarboxylate (DEAD), triphenylphosphine (Ph(3)P), and various acids. The new compounds exhibited potent in vitro growth inhibitory activity (IC (50) = 10-30 ng/mL) against both chloroquine sensitive (D-6) and chloroquine resistant (W-2) Plasmodium falciparum clones. Compound 6 (IC(50) = 6-8 ng/mL) is the most active compound of the class, the antimalarial efficacy of which is comparable to that of chloroquine. In general, this class of compound exhibited weak to moderate in vitro cytotoxicity against neuronal and macrophage cells with IC (50) in the range of 1-16 microg/mL and showed less toxicity in a colon cell line. Preliminary results indicated that compounds 3 and 6 are active against P. berghei, prolonged the life span of parasite-bearing mice from 6 days for untreated control to 16-24 days for drug-treated animals.     

Petasites hybridus extracts in vitro inhibit COX-2 and PGE2 release by direct interaction with the enzyme and by preventing p42/44 MAP kinase activation in rat primary microglial cells

Rhizomes of butterbur, Petasites hybridus L. (Asteraceae), have been used since ancient times for the treatment of inflammatory diseases. In the present study, the effects of lipophilic extracts from rhizomes of Petasites hybridus on the formation and release of prostaglandin E2 were investigated. The extracts had different contents of petasin and isopetasin: A: 2.1 % and 0.4 %, B: 0.2 % and 0.1 %, C: 12.1 % and 6.1 % and D: 21.9 % and 9.4 %, respectively. Direct inhibition of cyclooxygenase (COX) -1 and -2 isoenzymes and inhibition of the expression of COX-2 and p42/44 MAP kinase in rat primary microglial cells were tested. All extracts were found to be only weak direct inhibitors of COX-1 (IC50> 400 microg/mL). However, most extracts revealed a strong inhibitory activity against the inducible isoform COX-2 ( A: IC50=30.4 microg/mL; B: IC50=60.6 microg/mL; C: IC50=22.6 microg/mL; D: IC50=20.0 microg/mL). This activity was not correlated to the content of petasin and isopetasin. Pure petasin and isopetasin neither inhibited COX-1 nor COX-2 (IC50 > 400 microM for both compounds and enzymes). Petasites extracts dose-dependently inhibited LPS-induced and thus COX-2-mediated PGE2 release in primary rat microglial cells (A: IC50= 2.4 microg/mL; C: IC50=5.8 microg/mL and D: IC50=4.6 microg/mL). Also this effect was independent from the petasin and isopetasin content. COX-2 synthesis in microglia was totally blocked with 5 microg/mL of C whereas COX-1 synthesis was not influenced. C and D did not affect the LPS-induced activation of p38 MAPK and IkappaBalpha, but they prevented the LPS-induced activation of p42/44 MAPK. Therefore, these Petasites hybridus extracts can be regarded as natural selective inhibitors of COX-2 and its expression, an effect which is independent from the petasin content.     

Antiplasmodial activity of Uvaria klaineana

Crude extracts of Uvaria klaineana Engler and Diels (Annonaceae) stems showed in vitro activity against chloroquine-resistant K1 strain of Plasmodium falciparum. The most active extract was the basic dichloromethane extract containing crude alkaloids (IC50 = 3.55 microg/mL). The bioassay-guided fractionation of this extract led to the isolation of the major alkaloid crotsparine (1) which showed an antiplasmodial activity against the chloroquine-sensitive Thai strain of P. falciparum and the chloroquine-resistant K1 and FcB1 strains of P. falciparum. Two minor alkaloids were also identified as crotonosine (2) and zenkerine (3). Their structures were elucidated using 2D-NMR techniques.     

Antileishmanial and antibacterial activity of a new pyrazole derivative designated 4-[2-(1-(ethylamino)-2-methyl- propyl)phenyl]-3-(4-methyphenyl)-1-phenylpyrazole

Here, we report for the first time the synthesis and the antileishmanial activity of a new pyrazole derivative, namely 4-[2-(1-(ethylamino)-2-methylpropyl)phenyl]-3-(4-methyphenyl)-1-phenylpyrazole). Micromolar concentrations of this compound were found to inhibit the in vitro multiplication of Leishmania tropica, Leishmania major, and Leishmania infantum, three species causing different forms of leishmaniasis. Furthermore, the 50% inhibitory concentration (IC50) values for the compound are only slightly higher than those of amphotericin B, one of the most active antileishmanial agents used as a satisfactory substitute in cases not responding to pentostam. The IC50 values after 48 h for L. tropica, L. major, and L. infantum promastigote growth were 0.48 microg/mL, 0.63 microg/mL and 0.40 microg/mL, respectively for the compound, while they were 0.23 microg/mL, 0.29 microg/mL and 0.24 microg/mL, respectively for amphotericin B. We also tested this compound for its antibacterial activity against several bacteria. The strongest antibacterial activity was observed against Entrococcus feacalis and Staphylococcus aureus with a minimal inhibitory concentration (MIC) of 60 microg/mL.     

Inhibitory activities of prenylated flavonoids from Sophora flavescens against aldose reductase and generation of advanced glycation endproducts

Important targets for the prevention and treatment of diabetic complications include aldose reductase (AR) inhibitors (ARIs) and inhibitors of advanced glycation endproduct (AGE) formation. Here we evaluate the inhibitory activities of prenylated flavonoids isolated from Sophora flavescens, a traditional herbal medicine, on rat lens AR (RLAR), human recombinant AR (HRAR) and AGE formation. Among the tested compounds, two prenylated chalcones--desmethylanhydroicaritin (1) and 8-lavandulylkaempferol (2)--along with five prenylated flavanones--kurarinol (8), kurarinone (9), (2S)-2'-methoxykurarinone (10), (2S)-3beta,7,4'-trihydroxy-5-methoxy-8-(gamma,gamma-dimethylally)-flavanone (11), and kushenol E (13) were potent inhibitors of RLAR, with IC50 values of 0.95, 3.80, 2.13, 2.99, 3.77, 3.63 and 7.74 microM, respectively, compared with quercetin (IC50 7.73 microM). In the HRAR assay, most of the prenylated flavonoids tested showed marked inhibitory activity compared with quercetin (IC50 2.54 microM). In particular, all tested prenylated flavonols, such as desmethylanhydroicaritin (1, IC50 0.45 microM), 8-lavandulylkaempferol (2, IC50 0.79 microM) and kushenol C (3, IC50 0.85 microM), as well as a prenylated chalcone, kuraridin (5, IC50 0.27 microM), and a prenylated flavanone, (2S)-7,4'-dihydroxy-5-methoxy-8-(gamma,gamma-dimethylally)-flavanone (12, IC50 0.37 microM), showed significant inhibitory activities compared with the potent AR inhibitor epalrestat (IC50 0.28 microM). Interestingly, prenylated flavonoids 1 (IC50 104.3 microg mL(-1)), 2 (IC50 132.1 microg mL(-1)), 3 (IC50 84.6 microg mL(-1)) and 11 (IC50 261.0 microg mL(-1)), which harbour a 3-hydroxyl group, also possessed good inhibitory activity toward AGE formation compared with the positive control aminoguanidine (IC50 115.7 microg mL(-1)). Thus, S. flavescens and its prenylated flavonoids inhibit the processes that underlie diabetic complications and related diseases and may therefore have therapeutic benefit.