In Vivo, In Vitro and In Silico Anticancer Activity of Ilama Leaves: An Edible and Medicinal Plant in Mexico.

Ilama leaves are an important source of secondary metabolites with promising anticancer properties. Cancer is a disease that affects a great number of people worldwide. This work aimed to investigate the in vivo, in vitro and in silico anticancer properties of three acyclic terpenoids (geranylgeraniol, phytol and farnesyl acetate) isolated from petroleum ether extract of ilama leaves. Their cytotoxic activity against U-937 cells was assessed using flow cytometry to determine the type of cell death and production of reactive oxygen species (ROS). Also, a morphological analysis of the lymph nodes and a molecular docking study using three proteins related with cancer as targets, namely, Bcl-2, Mcl-1 and VEGFR-2, were performed. The flow cytometry and histomorphological analysis revealed that geranylgeraniol, phytol and farnesyl acetate induced the death of U-937 cells by late apoptosis and necrosis. Geranylgeraniol and phytol induced a significant increase in ROS production. The molecular docking studies showed that geranylgeraniol had more affinity for Bcl-2 and VEGFR-2. In the case of farnesyl acetate, it showed the best affinity for Mcl-1. This study provides information that supports the anticancer potential of geranylgeraniol, phytol and farnesyl acetate as compounds for the treatment of cancer, particularly with the potential to treat non-Hodgkin's lymphoma.

Advances in the Properties of Incomptine A: Cytotoxic Activity and Downregulation of Hexokinase II in Breast Cancer Cell Lines.

Breast cancer treatments are limited by the cancer subtype and its selectivity towards tumor cells, hence the importance of finding compounds that increase the survival of healthy cells and target any subtype. Incomptine A (IA) is a sesquiterpene lactone with demonstrated cytotoxic activity. In this study, through in vitro assays, it was observed that IA has similar cytotoxic activity between the subtypes triple negative, HER2+, and luminal A of the breast cancer cell lines. IA cytotoxic activity is higher in cancer than in nontumorigenic cells, and its selectivity index for cancer cells is more than that of the drug doxorubicin. Molecular docking and its in silico comparison with the 2-Deoxyglucose inhibitor suggest that IA could bind to Hexokinase II (HKII), decreasing its expression. Since we did not find changes in the expression of the glycolytic pathway, we suppose that IA could affect the antiapoptotic function of HKII in cancer cells. The IA-HKII union would activate the voltage-gated anion channel 1 (VDAC1), resuming apoptosis. Therefore, we suggest that IA could be used against almost any subtype and that its cytotoxic effect could be due to the reactivation of apoptosis in breast cancer cells.

Expanding the Study of the Cytotoxicity of Incomptines A and B against Leukemia Cells.

Heliangolide-type sesquiterpene lactones (HTSLs) are phytocompounds with several pharmacological activities including cytotoxic and antitumor activity. Both bioactivities are related to an α-methylene-γ-lactone moiety and an ester group on carbon C-8 in the sesquiterpene lactone (SL) structure. Two HTSLs, incomptines A (AI) and B (IB) isolated from Decachaeta incompta, were evaluated for their cytotoxic activity on three leukemia cell lines: HL-60, K-562, and REH cells. Both compounds were subjected to a molecular docking study using target proteins associated with cancer such as topoisomerase IIα, topoisomerase IIß, dihydrofolate reductase, methylenetetrahydrofolate dehydrogenase, and Bcl-2-related protein A1. Results show that IA and IB exhibit cytotoxic activity against all cell lines used. The CC50 value of IA was 2-4-fold less than etoposide and methotrexate, two anticancer drugs used as positive controls. The cytotoxic activity of IB was close to that of etoposide and methotrexate. The molecular docking analysis showed that IA and IB have important interaction on all targets used. These findings suggest that IA and IB may serve as scaffolds for the development of new treatments for different types of leukemia.

Understanding the Antilymphoma Activity of Annona macroprophyllata Donn and Its Acyclic Terpenoids: In Vivo, In Vitro, and In Silico Studies.

Annona macroprophyllata Donn (A. macroprophyllata) is used in traditional Mexican medicine for the treatment of cancer, diabetes, inflammation, and pain. In this work, we evaluated the antitumor activity of three acyclic terpenoids obtained from A. macroprophyllata to assess their potential as antilymphoma agents. We identified the terpenoids farnesyl acetate (FA), phytol (PT) and geranylgeraniol (Gg) using gas chromatography-mass spectroscopy (GC-MS) and spectroscopic (1H, and 13C NMR) methods applied to petroleum ether extract of leaves from A. macroprophyllata (PEAm). We investigated antitumor potential in Balb/c mice inoculated with U-937 cells by assessing brine shrimp lethality (BSL), and cytotoxic activity in these cells. In addition, to assess the potential toxicity of PEAm, FA, PT and Gg in humans, we tested their acute oral toxicity in mice. Our results showed that the three terpenoids exhibited considerable antilymphoma and cytotoxic activity. In terms of lethality, we determined a median lethal dose (LD50) for thirteen isolated products of PEAm. Gg, PT and AF all exhibited a higher lethality with values of 1.41 ± 0.42, 3.03 ± 0.33 and 5.82 ± 0.58 µg mL-1, respectively. To assess cytotoxic activity against U-937 cells, we calculated the mean cytotoxic concentration (CC50) and found that FA and PT were closer in respect to the control drug methotrexate (MTX, 0.243 ± 0.007 µM). In terms of antilymphoma activity, we found that FA, PT and Gg considerably inhibited lymph node growth, with median effective doses (ED50) of 5.89 ± 0.39, 6.71 ± 0.31 and 7.22 ± 0.51 mg kg-1 in females and 5.09 ± 0.66, 5.83 ± 0.50 and 6.98 ± 0.57mg kg -1 in males, respectively. Regarding acute oral toxicity, we classified all three terpenoids as category IV, indicating a high safety margin for human administration. Finally, in a molecular docking study of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, we found binding of terpenoids to some amino acids of the catalytic site, suggesting an effect upon activity with a resulting decrease in the synthesis of intermediates involved in the prenylation of proteins involved in cancer progression. Our findings suggest that the acyclic terpenoids FA, PT, and Gg may serve as scaffolds for the development of new treatments for non-Hodgkin's lymphoma.

Incomptine A Induces Apoptosis, ROS Production and a Differential Protein Expression on Non-Hodgkin's Lymphoma Cells.

Sesquiterpene lactones are of pharmaceutical interest due their cytotoxic and antitumor properties, which are commonly found within plants of several genera from the Asteraceae family such as the Decachaeta genus. From Decachaeta incompta four heliangolide, namely incomptines A-D have been isolated. In this study, cytotoxic properties of incomptine A (IA) were evaluated on four lymphoma cancer cell lines: U-937, Farage, SU-DHL-2, and REC-1. The type of cell death induced by IA and its effects on U-937 cells were analyzed based on its capability to induce apoptosis and produce reactive oxygen species (ROS) through flow cytometry with 4',6-diamidino-2-phenylindole staining, dual annexin V/DAPI staining, and dichlorofluorescein 2',7'-diacetate, respectively. A differential protein expression analysis study was carried out by isobaric tags for relative and absolute quantitation (iTRAQ) through UPLC-MS/MS. Results reveal that IA exhibited cytotoxic activity against the cell line U-937 (CC50 of 0.12 ± 0.02 µM) and the incubation of these cells in presence of IA significantly increased apoptotic population and intracellular ROS levels. In the proteomic approach 1548 proteins were differentially expressed, out of which 587 exhibited a fold-change ≥ 1.5 and 961 a fold-change ≤ 0.67. Most of these differentially regulated proteins are involved in apoptosis, oxidative stress, glycolytic metabolism, or cytoskeleton structuration.

Antihyperglycemic and Antilipidemic Properties of a Tea Infusion of the Leaves from Annona cherimola Miller on Streptozocin-Induced Type 2 Diabetic Mice.

The antihyperglycemic and antilipidemic effects of the tea infusion extracts of leaves from Annona cherimola Miller (IELAc-0.5, IELAc-1.5, and IELAc-3.0) were evaluated on normoglycemic (NG) and streptozocin-induced diabetic (STID) mice. In the acute test, IELAc-1.5 at 300 mg/kg bodyweight (bw) exhibited antihyperglycemic activity on STID mice since the first hour of treatment. Then, its antidiabetic potential was analyzed in a subchronic evaluation. IELAc-1.5 was able to reduce the blood glucose level, glycated hemoglobin (HbA1c), cholesterol (CHO), and triglycerides (TG); high-density lipoprotein (HDL) showed an increase at the end of treatment. IELAc-1.5 did not modify the urine profile at the end of the evaluation, and neither toxicity nor macroscopic organ damage were observed in acute and subchronic assays. In addition, a major flavonol glycoside present in the tea infusion extracts was identified using high-performance liquid chromatography with diode array detection (HPLC-DAD). The analysis of the tea infusion extracts by HPLC revealed that rutin was the major component. This study supports the use of tea infusions from Annona cherimola for the treatment of diabetes and suggests that rutin could be responsible, at least in part, for their antidiabetic properties.

Antihyperglycemic and Lipid Profile Effects of Salvia amarissima Ortega on Streptozocin-Induced Type 2 Diabetic Mice.

Salvia amarissima Ortega was evaluated to determinate its antihyperglycemic and lipid profile properties. Petroleum ether extract of fresh aerial parts of S. amarissima (PEfAPSa) and a secondary fraction (F6Sa) were evaluated to determine their antihyperglycemic activity in streptozo-cin-induced diabetic (STID) mice, in oral tolerance tests of sucrose, starch, and glucose (OSTT, OStTT, and OGTT, respectively), in terms of glycated hemoglobin (HbA1c), triglycerides (TG), and high-density lipoprotein (HDL). In acute assays at doses of 50 mg/kg body weight (b.w.), PEfAPSa and F6Sa showed a reduction in hyperglycemia in STID mice, at the first and fifth hour after of treatment, respectively, and were comparable with acarbose. In the sub-chronic test, PEfAPSa and F6Sa showed a reduction of glycemia since the first week, and the effect was greater than that of the acarbose control group. In relation to HbA1c, the treatments prevented the increase in HbA1c. In the case of TG and HDL, PEfAPSa and F6Sa showed a reduction in TG and an HDL increase from the second week. OSTT and OStTT showed that PEfAPSa and F6Sa significantly lowered the postprandial peak at 1 h after loading but only in sucrose or starch such as acarbose. The results suggest that S. amarissima activity may be mediated by the inhibition of disaccharide hydrolysis, which may be associated with an α-glucosidase inhibitory effect.

Antilymphoma Effect of Incomptine A: In Vivo, In Silico, and Toxicological Studies.

Incomptine A (IA) is a sesquiterpene lactone isolated from Decachaeta incompta that induces apoptosis, reactive oxygen species production, and a differential protein expression on the U-937 (diffuse histiocytic lymphoma) cell line. In this work, the antitumor potential of IA was investigated on Balb/c mice inoculated with U-937 cells and through the brine shrimp lethality (BSL) test. Furthermore, IA was subjected to molecular docking study using as targets proteins associated with processes of cancer as apoptosis, oxidative stress, and glycolytic metabolism. In addition to determining the potential toxicity of IA in human, its acute toxicity was performed in mice. Results reveals that IA showed high antilymphoma activity and BSL with an EC50 of 2.4 mg/kg and LC50 16.7 µg/mL, respectively. The molecular docking study revealed that IA has strong interaction on all targets used. In the acute oral toxicity, IA had a LD50 of 149 mg/kg. The results showed that the activities of IA including antilymphoma activity, BSL, acute toxicity, and in silico interactions were close to the methotrexate, an anticancer drug used as positive control. These findings suggest that IA may serve as a candidate for the development of a new drug to combat lymphoma.

Antitumor Potential of Annona muricata Linn. An Edible and Medicinal Plant in Mexico: In Vitro, In Vivo, and Toxicological Studies.

Annona muricata (Am) is a plant used in traditional Mexican medicine to treat cancer. In this study, ethanol extracts of Am collected in Acapulco and Tecpan from Guerrero state were evaluated orally on Balb/c mice inoculated with 4T1 cells, for cytotoxic activity (CA) on 4T1 cells, in brine shrimp lethality assay (BSLA), and for acute oral toxicity in mice. In addition, ethanol extracts were subjected to high-performance liquid chromatography (HPLC) with diode array detection. Results showed that the extracts collected in December in Acapulco (AcDe) and Tecpan (TeDe) exhibited the most significant antitumor and cytotoxic activity. In the BSLA, the most important effect was observed in the extracts from Acapulco and Tecpan collected in June (AcJu) and August (TeAg), respectively. The samples from Acapulco (AcJu, and AcAg) and Tecpan (TeJu and TeAg) showed the highest toxicity. The analysis of the extracts, AcDe and TeDe, by HPLC revealed that flavonoids, rutin, narcissin, and nicotinflorin were the major components. These findings suggest that extracts from Am collected in Acapulco and Tecpan in the month of December may be an important source to obtain flavonoid glycosides with anticancer potential specifically against breast cancer. This also supports the use of Am to treat cancer in Mexican traditional medicine.

Linearolactone and Kaempferol Disrupt the Actin Cytoskeleton in Entamoeba histolytica: Inhibition of Amoebic Liver Abscess Development.

Linearolactone (1) and kaempferol (2) have amebicidal activity in in vitro studies. The type of cell death induced by 1 and 2 and their effects on the virulence of E. histolytica were analyzed by transmission and confocal electron microscopy, reactive oxygen species (ROS) production, and apoptosis, detected by flow cytometry with dichlorofluorescein 2',7'-diacetate and annexin-V binding, respectively, and confirmed by TUNEL. The interaction of 1 and 2 with actin was analyzed by docking, and the in vivo amoebicidal activity was established with the Mesocricetus auratus model; amebic liver abscess (ALA) development was evaluated by magnetic resonance (MR) and validated post mortem. In vitro, compounds 1 and 2 caused chromatin condensation, intracellular ROS, and loss of actin structures. Coupling analysis showed that they bind to the allosteric and catalytic sites of actin with binding energies of -11.30 and -8.45 kcal/mol, respectively. Treatments with 1 and 2 induced a decrease in ALA formation without toxic effects on the liver and kidney. Thus, compound 1, but not 2, was able to induce apoptosis-like effects in E. histolytica trophozoites by intracellular production of ROS that affected the actin cytoskeleton structuration. In vivo, compound 1 was more active than compound 2 to reduce the development of ALA.

Ultrastructural and proapoptotic-like effects of kaempferol in Giardia duodenalis trophozoites and bioinformatics prediction of its potential protein target.

BACKGROUND: Kaempferol (KPF) is a flavonoid with antiparasitic activity including experimental giardiasis which mechanism of action is unknown. OBJECTIVE: To analyse the cytotoxic effects of KPF on Giardia duodenalis trophozoites and to identify a likely parasite target of this compound. METHODS: We used inhibitory concentrations of KPF (IC25, IC50 and IC100) and albendazole (ABZ) as reference drug. The ultrastructure of the trophozoites was analysed by transmission electron microscopy (TEM) whilst apoptosis/necrosis, production of reactive oxygen species (ROS) and cell cycle progression were assessed by flow cytometry (FCM) and confocal laser microscopy (CLM). Ligand-protein docking analyses were carried out using KPF structure from a drug library and crystal structure of a G. duodenalis aldose reductase (GdAldRed) homolog. RESULTS: KPF provoked appearance of perinuclear and periplasmic spaces devoid of cytosolic content and multilamellar structures. KPF induced proapoptotic death associated with partial arrest in the S phase without ROS production. Bioinformatics approaches predicted that GdAldRed is a viable KPF target (ΔG = -7.09 kCal/mol), exhibiting 92% structural identity and a similar coupling pattern as its human homolog. CONCLUSIONS: KPF exerted a proapoptotic effect on G. duodenalis trophozoites involving partial interruption of DNA synthesis without oxidative stress or structure damage to chromatin and cytoskeletal structures. GdAldRed is a likely target underlying its antigiardial activity.

Antihyperglycemic Effects of Annona diversifolia Safford and Its Acyclic Terpenoids: α-Glucosidase and Selective SGLT1 Inhibitiors.

Annona diversifolia Safford and two acyclic terpenoids were evaluated to determine their antihyperglycemic activity as potential α-glucosidase and selective SGLT-1 inhibitiors. Ethanolic extract (EEAd), chloroformic (CHCl3Fr), ethyl acetate (EtOAcFr), aqueous residual (AcRFr), secondary 5 (Fr5) fractions, farnesal (1), and farnesol (2) were evaluated on normoglycemic and streptozocin-induced diabetic mice. EEAd, CHCl3Fr, Fr5, (1) and (2) showed antihyperglycemic activity. The potential as α-glucosidase inhibitors of products was evaluated with oral sucrose and lactose tolerance (OSTT and OLTT, respectively) and intestinal sucrose hydrolysis (ISH) tests; the potential as SGLT-1 inhibitors was evaluated using oral glucose tolerance (OGTT), intestinal glucose absorption (IGA), and urinary glucose excretion (UGE) tests. In OSTT and OLTT, all treatments showed significant activity at two and four hours. In ISH, half maximal effective concentrations (CE50) of 565, 662 and 590 µg/mL, 682 and 802 µM were calculated, respectively. In OGTT, all treatments showed significant activity at two hours. In IGA, CE50 values of 1059, 783 and 539 µg/mL, 1211 and 327 µM were calculated, respectively. In UGE Fr5, (1) and (2) showed significant reduction of the glucose excreted compared with canagliflozin. These results suggest that the antihyperglycemic activity is mediated by α-glucosidase and selective SGLT-1 inhibition.

Structure and Absolute Configuration of Abietane Diterpenoids from Salvia clinopodioides: Antioxidant, Antiprotozoal, and Antipropulsive Activities.

The aerial parts of Salvia clinopodioides afforded abietanes 1a, 2a, and 3 (clinopodiolides A-C), two of which possess an unusual lactol moiety at C-19-C-20, together with an icetexane named clinopodiolide D (4a). Their structures were established by spectroscopic means, mainly 1H and 13C NMR, including 1D and 2D homo- and heteronuclear experiments. The antioxidant, antiprotozoal, and antidiarrheal effects of the isolates were evaluated. Compounds 2a and 3 showed better effects than α-tocopherol in the inhibition of lipid peroxidation with IC50 (µM) = 5.9 ± 0.1 and 2.7 ± 0.2, respectively, and moderate activity in the DPPH assay. All tested compounds showed moderate antiamoebic and antigiardial activity, as well as a good antipropulsive effect.

Structure-Activity Relationship Study of Acyclic Terpenes in Blood Glucose Levels: Potential α-Glucosidase and Sodium Glucose Cotransporter (SGLT-1) Inhibitors.

Twelve terpenoids were evaluated in the treatment of type 2 diabetes mellitus: seven monoterpenes (geranyl acetate (1), geranic acid (2), citral (3), geraniol (4), methyl geranate (5), nerol (6), and citronellic acid (7)), three sesquiterpenes (farnesal (8), farnesol (9), and farnesyl acetate (10)), one diterpene (geranylgeraniol (11)), and one triterpene (squalene (12)) were selected to carry out a study on normoglycemic and streptozotocin-induced diabetic mice. Among these, 2, 3, 7, 8, 9, and 10 showed antihyperglycemic activity in streptozotocin-induced diabetic mice. They were then selected for evaluation in oral sucrose and lactose tolerance tests (OSTT and OLTT) as well as in an oral glucose tolerance test (OGTT). In the OSTT and OLTT, compounds 3, 7, 8, 9, and 10 showed a reduction in postprandial glucose peaks 2 h after a sucrose or lactose load (comparable to acarbose). In the case of the OGTT, 2, 7, 8, 9, and 10 showed a reduction in postprandial glucose peaks 2 h after a glucose load (comparable to canagliflozin). Our results suggest that the control of postprandial hyperglycemia may be mediated by the inhibition of disaccharide digestion, such as sucrose and lactose, and the regulation of the absorption of glucose. The first case could be associated with an ∝ -glucosidase inhibitory effect and the second with an inhibition of the sodium-glucose type 1 (SGLT-1) cotransporter. Finally, five acyclic terpenes may be candidates for the development and search for new α-glucosidase and SGLT-1 cotransporter inhibitors.

Further Thymol Derivatives from Ageratina cylindrica.

From the leaves of Ageratina cylindrica, in addition to the described [(2S)-2-{4-formyl-5-hydroxy-2-[(2-methylpropanoyl)oxy]phenyl}oxiran-2-yl]methyl benzoate (cylindrinol A, 8), seven new thymol derivatives were isolated and named cylindrinols B - H (1 - 7). The structures of these compounds were established as (2-{4-(hydroxymethyl)-2-[(2-methylpropanoyl)oxy]phenyl}oxiran-2-yl)methyl benzoate (1), (2-{4-formyl-2-[(2-methylpropanoyl)oxy]phenyl}oxiran-2-yl)methyl benzoate (2), (2-{4-[(acetyloxy)methyl]-2-[(2-methylpropanoyl)oxy]phenyl}oxiran-2-yl)methyl benzoate (3), [2-(2-[(2-methylpropanoyl)oxy]-4-{[(2-methylpropanoyl)oxy]methyl}phenyl)oxiran-2-yl]methyl benzoate (4), [2-(5-hydroxy-2-[(2-methylpropanoyl)oxy]-4-{[(2-methylpropanoyl)oxy]methyl}phenyl)oxiran-2-yl]methyl benzoate (5), 2-{4-(hydroxymethyl)-2-[(2-methylpropanoyl)oxy]phenyl}prop-2-en-1-yl benzoate (6), and 2-hydroxy-2-[2-hydroxy-4-(hydroxymethyl)-phenyl]-3-[(2-methylpropanoyl)oxy]propyl benzoate (7), by spectroscopic means. Compounds 1 showed moderate antiprotozoal activity on both protozoa. Compounds 4 and 5 showed selectivity on Giardia lamblia trophozoites. All isolated compounds were less active than two antiprotozoal drugs, metronidazole and emetine, used as positive controls. Compound 5 exhibited a high inhibitory effect on hyperpropulsive movement of the small intestine in rats; its effect was best than loperamide, antidiarrheal drug used as a positive control.

Antidiarrheal Thymol Derivatives from Ageratina glabrata. Structure and Absolute Configuration of 10-Benzoyloxy-8,9-epoxy-6-hydroxythymol Isobutyrate.

Chemical investigation of the leaves from Ageratina glabrata yielded four new thymol derivatives, namely: 10-benzoyloxy-8,9-dehydro-6-hydroxythymol isobutyrate (4), 10-benzoyloxy-8,9-dehydrothymol (5), 10-benzoyloxythymol (6) and 10-benzoyloxy-6,8-dihydroxy-9-isobutyryl-oxythymol (7). In addition, (8S)-10-benzoyloxy-8,9-epoxy-6-hydroxythymol isobutyrate (1), together with other two already known thymol derivatives identified as 10-benzoyloxy-8,9-epoxy-6-methoxythymol isobutyrate (2) and 10-benzoyloxy-8,9-epoxythymol isobutyrate (3) were also obtained. In this paper, we report the structures and complete assignments of the ¹H and (13)C-NMR data of compounds 1-7, and the absolute configuration for compound 1, unambiguously established by single crystal X-ray diffraction, and evaluation of the Flack parameter. The in vitro antiprotozoal assay showed that compound 1 and its derivative 1a were the most potent antiamoebic and antigiardial compounds. Both compounds showed selectivity and good antiamoebic activity comparable to emetine and metronidazole, respectively, two antiprotozoal drugs used as positive controls. In relation to anti-propulsive effect, compound 1 and 1a showed inhibitory activity, with activities comparable to quercetin and compound 9, two natural antipropulsive compounds used as positive controls. These data suggest that compound 1 may play an important role in antidiarrheal properties of Ageratina glabrata.

ent-Kaurene Glycosides from Ageratina cylindrica.

The aqueous extract of the leaves of Ageratina cylindrica afforded six new ent-kaurenoic acid glycosides together with the known diterpenoid paniculoside V, the flavonoid astragalin, chlorogenic acid, and L-chiro-inositol. The structures were elucidated mainly by NMR and MS methods, and the absolute configuration was established by vibrational circular dichroism spectroscopy. The new compounds showed moderate antiprotozoal activity against Entamoeba histolytica and Giardia lamblia trophozoites.

Antiamoebic and Antigiardial Activity of Clerodane Diterpenes from Mexican Salvia Species Used for the Treatment of Diarrhea.

Terpenoids from Salvia species have been identified to possess biological properties as antiprotozoal agents. Here, we evaluated the antiamoebic and antigiardial activities of 14 known clerodane and modified clerodane-type diterpenes isolated from five Mexican Salvia species against Entamoeba histolytica and Giardia lamblia, and analyzed the effects of the functionalities in decalin ring or in the whole clerodane framework to visualize the structural requirements necessary to produce an antiprotozoal activity. Among these, linearolactone was the most active clerodane diterpene against both protozoa with IC50 values of 22.9 µM for E. histolytica and of 28.2 µM in the case of G. lamblia. In this context it may be a lead compound for the development of novel therapeutic agent for the treatment of diarrhea and dysentery. The remaining diterpenes assayed showed moderate to weak activity against both protozoa. These findings give support to the use of Salvia species in the traditional medicine from México for the treatment of diarrhea.

Antiprotozoal activity of 8-acyl and 8-alkyl incomptine A analogs.

The activities of 11 C-8-O-acyl and alkyl analogs of the antiprotozoal sesquiterpene lactone, incomptine A (1) against Entamoeba histolytica and Giardia lamblia, were determined. Here, the effects of different lengths and amounts of branching of the acyl and alkyl groups on the antiprotozoal activity of the synthesized incomptine A-analogs are reported.

Synthesis of 3-tetrazolylmethyl-4H-chromen-4-ones via Ugi-azide and biological evaluation against Entamoeba histolytica, Giardia lamblia and Trichomona vaginalis.

The synthesis of novel 3-tetrazolylmethyl-4H-chromen-4-ones via an Ugi-azide multicomponent reaction and their biological evaluation against Entamoeba histolytica, Giardia lamblia and Trichomona vaginalis are described. Reported yields are moderate to good and biological results show that these compounds could be considered as candidates to anti-parasitic drugs, especially against G. lamblia.