Activity of extracts and isolated naphthoquinones from Kigelia pinnata against Plasmodium falciparum

Four naphthoquinoids from Kigelia pinnata rootbark were assessed in vitro against chloroquine-sensitive (T9-96) and -resistant (K1) Plasmodium falciparum strains and for cytotoxicity using KB cells. 2-(1-Hydroxyethyl)naphtho[2,3-b]furan-4,9-dione possessed good activity against both strains [IC(50) values 627 nM (K1), 718 nM (T9-96)]. Isopinnatal, kigelinol, and isokigelinol exhibited lower activity against both strains.     

Antiprotozoal activity of aporphine alkaloids isolated from Unonopsis buchtienii (Annonaceae)

On a preliminary screening, substantial leishmanicidal activity was observed for the petroleum ether and alkaloidal extracts of the stem bark of Unonopsis buchtienii, the alkaloids and sterols isolated from these were studied. Of the alkaloids, liriodenine exhibited the highest activity against Leishmania major and L donovani (IC100 = 3.12 micrograms/mL). On the other hand, O-methylmoschatoline and the petroleum ether extract without alkaloids showed an interesting in vitro activity against Trypanosoma brucei with an IC100 of 6.25 micrograms/mL. The highest cytotoxic activities were found with the petroleum ether extracts without alkaloids and with all alkaloids isolated (IC50 < 9 micrograms/mL for Vero cell line).     

Cytotoxic activity of amooranin and its derivatives

Amooranin, 25-hydroxy-3-oxoolean-12-en-28-oic acid, is a triterpene acid isolated from Amoora rohituka stem bark. The cytotoxic effects of amooranin and its derivatives were studied. Amooranin and its methyl ester showed greater cytotoxicity against MCF-7 and HeLa cells derived from tumour tissues with a 50% inhibitory concentration (IC(50)) of 1.8-3.4 microg/mL, compared with Chang liver cells from normal tissue with an IC(50) of 6.2-6.4 microg/mL, but amooranin exhibited no activity on HEp-2 and L-929 cells. However, its monoacetate derivative showed no inhibitory activity at 1-10 microg/mL dose levels. Of the cytotoxic isolates, the methyl ester derivative was inactive in in vivo evaluations in the Ehrlich ascites tumour cells at 50 and 100 mg/kg/day, demonstrating T/C values of 106% and 114%, respectively.     

Evaluation of the in vitro antimalarial activity of Picralima nitida extracts.

Extracts of Picralima nitida seeds, fruit rind, and stem bark have been investigated in vitro for antimalarial activity. The extracts showed remarkable inhibitory activity against drug resistant clones of Plasmodium falciparum at doses of 1.23-32 micrograms/ml. The dichloromethane extract of the fruit rind was the most active of the crude extracts, with IC50 values of 1.61 micrograms/ml for the Indochina (W-2), clone and 2.41 micrograms/ml for the Sierra Leone (D-6), clone. An alkaloid fraction obtained from the methanol extract of the stem bark gave an IC50 value of 2.00 micrograms/ml and 1.23 micrograms/ml in the W-2 and D-6 clones, respectively. The result supports the continued ethnomedical exploration of the plant as a potential antimalarial drug.     

Indiosides G-K: steroidal glycosides with cytotoxic and anti-inflammatory activities from Solanum violaceum

Five new steroidal glycosides (1-5) and nine known compounds were isolated from Solanum violaceum. Indiosides G (1) and H (2) are spirostene saponins with an iso-type F ring, indioside I (3) is a spirostane saponin, and indiosides J (4) and K (5) are unusual furostanol saponins with a deformed F ring. These structures represent rare naturally occurring steroidal skeletons. The structures of the new compounds were elucidated using 1D and 2D spectroscopic techniques and acid hydrolysis. Compounds 2, 3, and 7-9 exhibited cytotoxic activity against six human cancer cell lines (HepG2, Hep3B, A549, Ca9-22, MDA-MB-231, and MCF-7) with IC(50) values of 1.83-8.04 μg/mL. Steroidal saponins 3, 8, and 9 showed inhibitory effects on superoxide anion generation with IC(50) values of 2.84 ± 0.18, 0.62 ± 0.03, and 1.62 ± 0.59 μg/mL, respectively. Saponins 8 and 9 also inhibited elastase release with IC(50) values of 111.05 ± 7.37 and 4.04 ± 0.51 μg/mL, respectively. Structure-activity relationship correlations of these compounds with respect to cytotoxic and anti-inflammatory effects are discussed.     

Cytotoxic 3,20-epoxy-ent-kaurane diterpenoids from Isodon eriocalyx var. laxiflora

Four new ent-kaurane diterpenoids, laxiflorins J-M (1-4), along with maoecrystal A (5) and maoecrystal P (6), were isolated from the leaves of Isodon eriocalyx var. laxiflora. Their structures were determined by spectroscopic analyses. All the compounds were assayed for their cytotoxic effects on human tumor K562, A549, and T24 cell lines. Compounds 1 and 6 showed significant inhibitory effects on human tumor K562 and T24 cells, with IC(50) values less than 0.5 microg/mL. Compound 3 also demonstrated cytotoxic activities against all three types of human tumor cells, with IC(50) values in the range of 1-25 microg/mL.     

Evaluation of antiprotozoal and plasmodial enoyl-ACP reductase inhibition potential of turkish medicinal plants

A total of 58 extracts of different polarity were prepared from various organs of 16 species of Turkish plants and screened for their antitrypanosomal, antileishmanial and antiplasmodial activities. No significant activity was observed against Trypanosoma cruzi, whereas many extracts showed appreciable trypanocidal potential against T. brucei rhodesiense, with the CHCl(3)-soluble portion of Phlomis kurdica being the most active (IC(50) 2.7 microg[sol ]mL). Almost all extracts, particularly the CHCl(3) phases, exhibited growth inhibition activity against Leishmania donovani amastigotes. The CHCl(3)-solubles of Putoria calabrica roots (IC(50) 1.9 microg[sol ]mL), Wendlandia ligustroides leaves (IC(50) 2.1 microg[sol ]mL) and Rhododendron luteum leaves (IC(50) 2.3 microg[sol ]mL) displayed the highest leishmanicidal potential. The majority of the extracts also possessed antiplasmodial activity against the multi-drug resistant K1 Plasmodium falciparum strain. The most potent antiplasmodial activity was observed with the CHCl(3) extracts of Phlomis kurdica (IC(50) 1.5 microg[sol ]mL), P. leucophracta (IC(50) 1.6 microg[sol ]mL), Scrophularia cryptophila (IC(50) 1.8 microg[sol ]mL), Morina persica (IC(50) 1.9 microg[sol ]mL) and the aqueous root extract of Asperula nitida subsp. subcapitellata (IC(50) 1.6 microg[sol ]mL). Twenty-one extracts with significant antimalarial activity (IC(50) < 5 microg[sol ]mL) were also tested for their ability to inhibit the purified enoyl-ACP reductase (FabI), a crucial enzyme in the fatty acid biosynthesis of P. falciparum. The CHCl(3) extract of Rhododendron ungernii leaves (IC(50) 10 microg[sol ]mL) and the H(2)O-soluble portion of Rhododendron smirnovii leaves (IC(50) 0.4 microg[sol ]mL) strongly inhibited the FabI enzyme. The preliminary data indicate that some (poly)phenolic compounds are responsible for the FabI inhibition potential of these extracts. The presented work reports for the first time the antiprotozoal activity of nine different genera as well as a target specific antimalarial screening for the identification of P. falciparum FabI inhibitors from medicinal plant extracts.     

Cyclic peroxides derived from the marine sponge Plakortis simplex

Two new cyclic peroxides, 2 and 3, were isolated from a sample of the Norwegian sponge Plakortis simplex. Their structures including relative stereochemistry were elucidated by interpretation of MS and NMR data. Compound 3 exhibited moderate in vitro activity against six solid human tumor cell lines with IC50 values in the range 7-15 microg/mL.     

Cytotoxic dihydroagarofuranoid sesquiterpenes from the stem of Microtropis fokienensis

Four dihydroagarofuran sesquiterpene polyesters (1-4) have been isolated from the stem of Microtropis fokienensis. The structures of these new compounds were determined through spectroscopic analyses. Compound 1, 2, 3, and 4 exhibited cytotoxicities (IC(50) values < 0.1 microg/mL) against P-388 and HT-29 cell lines in vitro.     

Cytotoxic and antioxidant activities of alkylated benzoquinones from Maesa lanceolata

The natural and semi-synthetic analogs of substituted 1,4-benzoquinones were evaluated for in vitro cytotoxic and antioxidant activities. Maesanin, dihydromaesanin, maesanin dimethyl ether and isomeric mixtures of 3-[(Z)-10'-pentadecenyl]-benzoquinone derivatives exhibited cytotoxic activity against HL-60 cell line (IC50 values 4.5, 2.2, 0.43 and 2.8 microg/mL, respectively), while it was found to be inactive against ROS (Reactive Oxygen Species) generation in HL-60. In contrast, the isomeric acylated benzoquinones with shorter alkyl substituents, namely, 2-acetoxy-5-hydoxy-6-methyl-3-tridecyl-1,4-benzoquinone and 2-hydoxy-5-acetoxy-6-methyl-3-tridecyl-1,4-benzoquinone showed most prominent antioxidant and antiproliferative effect on HL-60 (IC50 values 6.2 and 2.2 microg/mL, respectively), as well as cytotoxicities against SK-MEL, KB, BT-549 and SK-OV-3 carcinomas (IC50 values <1.1-4.2 microg/mL). All benzoquinones were found to be inactive against cell aggregation and cell adhesion assays, thus showing no effect on immune responses and inflammation.     

Antiplasmodial triterpenes from twigs of Gardenia saxatilis

Ten triterpenes (1-10) were isolated and identified from the twigs of Gardenia saxatilis (Rubiaceae) and were subjected to antiplasmodial evaluation against the parasite Plasmodium falciparum. The first six compounds, lupenone (1), lupeol (2), betulinic acid (3), oleanolic acid (4), ursolic acid (5), and winchic acid (27-O-feruloyloxybetulinic acid) (6) were inactive in the assay. The other four compounds, messagenic acid A (7) and messagenic acid B (8), the 27-O-p-(Z)- and 27-O-p-(E)-coumarate esters of betulinic acid, and a mixture of uncarinic acid E (27-O-p-(E)-coumaroyloxyoleanolic acid) (9) and 27-O-p-(E)-coumaroyloxyursolic acid (10) exhibited antiplasmodial activity, with the IC50 values of 1.5, 3.8 and 2.9 microg/ml, respectively. The results indicated that the p-coumarate moieties at the 27-position, both the cis and trans isomers, contributed to antiplasmodial activity. Introduction of a methoxyl group to the 3-position of the p-coumarate moiety to give a ferulate moiety resulted in loss of activity.     

Antimalarial activity and cytotoxicity of Evodia fatraina stem bark extracts

Stem bark extracts of Evodia fatraina (Rutaceae) were tested for antimalarial activity in vitro on Plasmodium falciparum using an isotopic semi-microtest and in vivo on Plasmodium berghei in mice. Ethyl acetate extract showed moderate antimalarial activity in vitro (IC50 = 8.5 micrograms ml-1). However, ethanolic extract exhibited significant potency in vivo (65% suppression of parasitaemia). Moreover, low toxicity against HeLa cells and L 929 fibroblasts was observed with ethanolic extract (IC50 = 95 micrograms ml-1 and 60 micrograms ml-1, respectively).     

Three new peroxides from the sponge Plakinastrella species.

Two new five-membered-ring peroxide acids, plakinic acid F (3) and epiplakinic acid F (4), and a new peroxide-lactone, plakortolide F (5), were isolated from a sponge of the genus Plakinastrella collected from Felicite Island, Seychelles. The structures were elucidated through spectral analysis. The free acids 3 and 4 exhibit moderate antifungal activity against Candida albicans with minimum inhibitory concentrations of 25 micrograms/mL (SDB) and 3.1 micrograms/mL (RPMI) for 3, and 25 micrograms/mL (SDB) and 6.25 micrograms/mL (RPMI) for 4, respectively. Both also showed moderate in vitro inhibition of Aspergillus fumigatus with IC90's of 25 micrograms/mL.     

Neocrotocembranal from Croton oblongifolius.

A new cembranoid diterpene, neocrotocembranal (3), was isolated from the stem bark of Croton oblongifolius. Its structure was established on the basis of spectroscopic analysis. This compound inhibited platelet aggregation induced by thrombin, with an IC50 value of 47.21 microg/mL, and exhibited cytotoxicity against P-388 cells in vitro, with an IC(50) value of 6.48 microg/mL.     

Marinoquinolines A-F, pyrroloquinolines from Ohtaekwangia kribbensis (Bacteroidetes)

Marinoquinoline A (1) was isolated from the gliding bacterium Ohtaekwangia kribbensis together with the novel marinoquinolines B-F (2-6). Their structures were elucidated from NMR and HRESIMS data. The pyrroloquinolines showed weak antibacterial and antifungal activities and moderate cytotoxicity against four growing mammalian cell lines with IC(50) values ranging from 0.3 to 8.0 μg/mL. In a screening against tropical parasites marinoquinolines A-F (1-6) showed activity against Plasmodium falciparum K1 with IC(50) values between 1.7 and 15 μM.     

Antimalarial, antiviral, and antitoxoplasmosis norsesterterpene peroxide acids from the Red Sea sponge Diacarnus erythraeanus

A new norsesterterpene acid, named muqubilone (1), along with the known sigmosceptrellin-B and muqubilin were isolated from the Red Sea sponge Diacarnus erythraeanus. The structure determination of 1 was based primarily on 1D and 2D NMR analyses. Sigmosceptrellin-B exhibits significant in vitro antimalarial activity against Plasmodium falciparum (D6 and W2 clones) with IC(50) values of 1200 and 3400 ng/mL, respectively. Muqubilin and 1 show in vitro antiviral activity against herpes simplex type 1 (HSV-1) with ED(50) values of 7.5 and 30 microg/mL, respectively. Muqubilin and sigmosceptrellin-B display potent in vitro activity against Toxoplasma gondii at a concentration of 0.1 microM without significant toxicity.     

Dehydrozingerone, chalcone, and isoeugenol analogues as in vitro anticancer agents

Twenty-eight compounds related to dehydrozingerone (1), isoeugenol (3), and 2-hydroxychalcone (4) were synthesized and evaluated in vitro against human tumor cell replication. Except for isoeugenol analogues 27-35, most compounds exhibited moderate or strong cytotoxic activity against KB, KB-VCR (a multidrug-resistant derivative), and A549 cell lines. In particular, chalcone 15 showed significant cytotoxic activity against the A549 cell line with an IC50 value of 0.6 microg/mL. Furthermore, dehydrozingerone analogue 11 and chalcones 16 and 17 showed significant and similar cytotoxic activity against both KB (IC50 values of 2.0, 1.0, and 2.0 microg/mL, respectively) and KB-VCR (IC50 values of 1.9, 1.0, and 2.0 microg/mL, respectively) cells, suggesting that they are not substrates for the P-glycoprotein drug efflux pump.     

New bioactive prenylflavonoids and dibenzocycloheptene derivative from roots of Dendrolobium lanceolatum

Two new flavanones (1 and 2), a new flavan (3), and a new rare dibenzocycloheptene derivative (4) together with a known flavan, 4'-hydroxy-2' ',2' 'dimethyl-pyranoflavan (5), were isolated from the roots of Dendrolobium lanceolatum. Their structures were established on the basis of spectral evidence, and an X-ray analysis was performed to confirm the structure of 4. Compounds 1-3 exhibited antimalarial activity with IC50 values of 2.6, 3.3, and 3.1 microg/mL, respectively. Compounds 1-5 showed moderate antimycobacterial activity with MIC values of 6.3, 12.5, 25, 25, and 50 microg/mL, respectively. In addition, 1 showed strong cytotoxicity against cancer cell lines KB, BC, and NCI-H187 with IC50 values of 1.2, 1.6, and 0.6 microg/mL, respectively, while 2 showed moderate cytotoxicity against the NCI-H187 cell line with an IC50 value of 8.1 microg/ mL.     

Potent antiviral potamogetonyde and potamogetonol, new furanoid labdane diterpenes from Potamogeton malaianus

New furanoid labdane diterpenes, potamogetonyde (3) and potamogetonol (4), together with two known compounds, potamogetonin (1) and 15,16-epoxy-12-oxo-8(17),13(16),14-labdatrien-20,19-olide (2), were isolated from the CH(2)Cl(2) extract of Potamogeton malaianus. The chemical structures of 1-4 were elucidated by the analyses of their spectral data, mainly by 1D and 2D NMR techniques. Potamogetonyde (3) and potamogetonol (4) exhibited potent antiviral (HSV-1) activity with respective IC(50) values of 8 and 3 microg/mL. Compounds 1-4 possessed cytotoxicity toward insect cells (fall armyworm and mosquito larvae, IC(50) of 11-72 microg/mL). Furanoid diterpenes 3 and 4 also exhibited cytotoxicity against the Vero cell line with respective IC(50)'s of 31 and 28 microg/mL, while 1 and 2 were inactive at 50 microg/mL. Compounds 1-4 were inactive (at 20 microg/mL) against KB and BC cell lines and showed only weak antimycobacterial activity against Mycobacterium tuberculosis H37Ra with minimum inhibitory concentrations of 50-100 microg/mL.     

Bioactive carbazole alkaloids from Clausena wallichii roots

Four new carbazole alkaloids, clausenawallines C-F (1-4), along with 18 known compounds (5-22) were isolated from the roots of Clausena wallichii. Compounds 3, 9, and 22 exhibited significant antibacterial activity against methicillin-resistant Staphylococcus aureus SK1 (MRSA SK1) and Staph. aureus TISTR 1466 with MIC values in the range 4-16 μg/mL, whereas compound 4 showed the highest cytotoxicity against oral cavity cancer (KB) and small-cell lung cancer (NCI-H187) with IC(50) values of 10.2 and 4.5 μM, respectively.