piperidines and cassine

In previous studies, Cassia spectabilis DC leaf has shown a good antiplasmodial activity. Therefore, this study is a follow-up study of the extract of leaf of C. spectabilis DC on its in vitro and in vivo antiplasmodial activity and mechanism as an antimalarial.. The extract was fractionated, sub-fractionated and isolated to obtain the purified compound. In vitro antiplasmodial activity test against Plasmodium falciparum to find out the active compound. In vivo test against P. berghei ANKA-infected mice was conducted to determine prophylactic activity and antiplasmodial activity either alone or in combination with artesunate. The inhibition of heme detoxification test as one of the antimalarial mechanisms was carried out using the Basilico method.. C. spectabilis DC leaf possessed potent antiplasmodial activity and may offer a potential agent for effective and affordable antimalarial phytomedicine.

Topics: Animals; Antimalarials; Artesunate; Cassia; Chloroquine; Heme; Ketones; Malaria; Male; Mice, Inbred BALB C; Phytotherapy; Piperidines; Plant Extracts; Plant Leaves; Plasmodium berghei; Plasmodium falciparum

Cancer is one of the most critical problems of public health in the world and one of the main challenges for medicine in this century. Unfortunately, most patients are diagnosed at advanced stage, when the treatment options are palliative. Consequently, the search for novel therapeutic options is imperative. In the context, the plants represent an important source for discovering of novel compounds with pharmacological potential including antineoplastic agents. Herein, we aimed to investigate in vitro antiproliferative and cytotoxic potentials of an alkaloid mixture derived from Senna spectabilis, (−)-cassine (1) and (−)-spectaline (2). These alkaloids reduced cell viability in a concentration-dependent manner of six tumor cell lines. From initial screening, HepG2 cells were selected for further investigations. We show that alkaloids 1/2 have an important antiproliferative activity on HepG2 cells due to their ability in inducing cell cycle arrest in G1/S transition. This effect was associated to ERK inactivation and down-regulation of cyclin D1 expression. In addition, we evidenced a disruption of the microfilaments and microtubules in a consequence of the treatment. Taken together, the data showed by the first time that alkaloids 1/2 strongly inhibit cell proliferation of hepatocellular carcinoma cells. Therefore, they represent promise antitumor compounds against liver cancer and should be considered for further anticancer in vivo studies.

Topics: Antineoplastic Agents; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cyclin D1; Down-Regulation; Extracellular Signal-Regulated MAP Kinases; Flowers; Humans; Ketones; Piperidines; Senna Plant

In this work, we present the in vitro schistosomicidal activity evaluation of the most active dichloromethane fraction (FDm) (ED50=83.5μg/mL) and of a mixture of the major alkaloids ((-)-cassine/(-)-spectaline, C/E) (ED50=37.4μg/mL) from the flowers of Senna spectabilis against adult worms and cercariae. We also demonstrate other toxic effects including paralysis of the adult worms, inhibition of the secretory activity, tegument lesions and cercaricidal activity. In the association test of Praziquantel (PZQ)-C/E, we observed up to 80% mortality of Schistosoma mansoni in comparison to PZQ monotherapy. Due to the diversity of the toxic effects, the schistosomicidal activity of C/E is likely a result of a multitarget mechanism involving the tegument, secretory system and neuromotor action.

Topics: Alkaloids; Animals; Fabaceae; Female; Flowers; Ketones; Male; Motor Activity; Piperidines; Plant Extracts; Schistosoma mansoni; Schistosomicides; Stereoisomerism

Senna spectabilis (sin. Cassia excelsa, C. spectabilis) is an endemic tree of South America and Africa, very common in Brazil, where it is known as "canafistula-de-besouro" and "cassia-do-nordeste". In folk medicine, this plant is indicated for the treatment of constipation, insomnia, anxiety, epilepsy, malaria, dysentery and headache. Phytopharmacological studies have also confirmed anticonvulsive, sedative, anti-malarial, antimicrobial and cytotoxic properties of many parts of S. spectabilis. In this communication, we present a comparative study of the leishmanicidal activity of the crude ethanolic extract, its fractions and also the two major alkaloidal metabolites (-)-cassine/(-)-spectaline, trying to establish a relationship between the presence of piperidine alkaloidal constituents and leishmanicidal activity. The growth inhibitory effect of promastigote forms of Leishmania major was determined for the crude extract, fractions of the flowers of S. spectabilis and a mixture of (-)-cassine/(-)-spectaline in comparison to pentamidine used as standard drug. The cytotoxic effects were assessed on macrophage strain J774 by lactate dehydrogenase assay. Fractions dichloromethane (FL-DCM) and n-butanol (FL-Bu) and a mixture of (-)-cassine/(-)-spectaline (∼7:3) exhibited significant activity against the parasite Leishmania major (IC50 values of 0.6±0.1 μg/ml, 1.6±0.9 μg/ml and 24.9±1.4 μg/ml, respectively), without toxic effects on murine macrophages. Due to the promising results elicited, further studies in vivo need to be performed to confirm the therapeutic potential of Senna spectabilis.

Topics: Antiparasitic Agents; Flowers; Ketones; Leishmania major; Leishmaniasis; Life Cycle Stages; Medicine, Traditional; Pentamidine; Piperidines; Plant Extracts; Senna Plant

Medicinal plants represent an important opportunity to rural communities in Africa, as a source of affordable medicine and as a source of income. Increased patient awareness about safe usage is important as well as more training with regards to traditional medicine. The aim of this study was to evaluate the ethnomedicinal prowess of some indigenous South African plants commonly used in Eastern Cape Province of South Africa for the treatment of skin and respiratory tract infections, HIV and their toxicity potential.. Cassine transvaalensis, Vangueria infausta, Croton gratissimus and Vitex ferruginea were tested for antibacterial activities against Staphylococcus aureus and Staphylococcus epidermidis using Kirby-Bauer disk diffusion and minimum inhibition concentration (MIC). Cytotoxic and anti-HIV-1 activities of plants were tested using MTT Assay (3- (Dimethylthiozole-2-yl-2,5-diphenyltetrazolium bromide)) and anti- HIV-1iib assay. In search of bioactive lead compounds, Cassine transvaalensis which was found to be the most active plant extract against the two Staphylocoous bacteria was subjected to various chromatographic. Thin layer chromatography, Column chromatography and Nuclear Magnetic Resonance (NMR), (1H-1H, 13C-13C, in DMSO_d6, Bruker 600 MHz) were used to isolate and characterize 3-Oxo-28-hydroxylbetuli-20(29)-ene and 3,28-dihydroxylbetuli-20(29)-ene bioactive compounds from C. transvaalensis.. The four plants studied exhibited bioactive properties against the test isolates. The zones of inhibition ranged between 16 mm to 31 mm for multi-drug resistant staphylococci species. MIC values varied between 0.6 and 0.02 μg/ml. C. gratissimus and C. transvaalensis exhibited the abilities to inhibit HIV-1iib. Two bioactive compounds were isolated from C. transvaalensis.. Data from this study reveals the use of these plant by traditional healers in the Eastern Cape. Furthermore, C. transvaalensis and C. gratissimus were found to be more active as against HIV-1iib. While C. transvaalensis was most active against the two Staphylococcus bacteria.

Topics: Anti-Bacterial Agents; Anti-HIV Agents; Celastraceae; Chromatography, Thin Layer; Croton; HIV Infections; HIV-1; Humans; Ketones; Medicine, African Traditional; Microbial Sensitivity Tests; Piperidines; Plant Extracts; Plants, Medicinal; Rubiaceae; South Africa; Staphylococcal Infections; Staphylococcus; Vitex; Wound Healing

Natural products have been revealed as relevant sources of therapeutic agents including those for the management of pain states. In this study, the anti-nociceptive and anti-inflammatory effects of (-)-cassine, isolated from Senna spectabilis were evaluated using pharmacological, behavioural and biochemical approaches. Oral treatment with (-)-cassine (3-30 mg/kg) reduced carrageenan-induced mechanical and thermal nociception associated with the suppression of myeloperoxidase activity in the mouse paw. Moreover, (-)-cassine (1-10 μg/site) prevented mechanical hyperalgesia induced by carrageenan when given through the intraplantar (i.pl.), spinal and intracerebroventricular routes. Additionally, oral treatment with (-)-cassine (3-60 mg/kg) prevented the mechanical hyperalgesia elicited by intraplantar injection of prostaglandin E(2), complete Freund's adjuvant, interleukin-1β, interleukin-6 and keratinocyte-derived chemokine. Furthermore, (-)-cassine inhibited the mechanical nociceptive response induced by ligation of the sciatic nerve and also significantly reduced the levels of cytokines/chemokines in paw tissue following i.pl. injection of carrageenan. In addition, the anti-nociceptive and anti-inflammatory actions of (-)-cassine were associated with its ability to interact with both TRPV1 and TRPA1 receptors and by inhibiting the upregulation of cyclooxigenase-2 as well as inhibiting the phosphorylation of MAPK/ERK and the transcription factor NF-κB. It is important to highlight that oral treatment with (-)-cassine did not produce any effects related to temperature, locomotor activity or catalepsy. Altogether, the present data demonstrate that (-)-cassine has systemic, spinal and supraspinal anti-nociceptive properties when assessed in inflammatory and neuropathic pain models. These effects are associated with its ability to block several signalling pathways associated with inflammatory and nociceptive responses. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.

Topics: Animals; Behavior, Animal; Carrageenan; Freund's Adjuvant; Hyperalgesia; Inflammation; Ketones; Male; Mice; Neuralgia; Pain Measurement; Pain Threshold; Piperidines

The depressant and anticonvulsant activities of iso-6-cassine (ISO) from Senna spectabilis (0.5, 1.0 and 1.5mg/kg) injected by oral route in mice caused a significant decrease in the motor activity of animals when compared with the control group, up to 30 days after the administration and at dose of 1.5mg/kg, it reduced the remaining time of animals on Rota-rod apparatus. Additionally, ISO at doses tested was also capable to promote an increase of latency for development of convulsions induced by pentylenetetrazole and picrotoxin. These results suggest possible depressant and anticonvulsant activities in mice that need further investigation.

Topics: Animals; Behavior, Animal; Central Nervous System; Dose-Response Relationship, Drug; Ketones; Male; Mice; Motor Activity; Pentylenetetrazole; Phytotherapy; Picrotoxin; Piperidines; Plant Extracts; Plant Leaves; Seizures; Senna Plant

Topics: Alkaloids; Alkylation; Amides; Anisomycin; Combinatorial Chemistry Techniques; Ketones; Lactams; Molecular Structure; Oxidation-Reduction; Piperidines; Pyrrolidines; Stereoisomerism

Methanol extracts of leaves, roots and bark of Senna racemosa (Mill.) H.S. Irwin & Barneby (syn. Cassia racemosa Mill.) were tested for antiprotozooal activity against Giardia intestinalis and Entamoeba histolytica. All of the tested extracts showed good activity against both protozoa species. Extracts from stem bark and leaves were most active, with an IC(50) of 2.10 microg/mL for Giardia intestinalis and 3.87 microg/mL for Entamoeba histolytica. Of the previously isolated compounds from Senna racemosa, the piperidine alkaloid cassine had greater activity against Giardia intestinalis with an IC(50) of 3.28 microg/mL and chrysophanol, a 1,8-dihydroxy-anthraquinone, was the most active agent against Entamoeba histolytica, with an IC(50) of 6.21 microg/mL.

Topics: Animals; Anthraquinones; Antiprotozoal Agents; Entamoeba histolytica; Giardia lamblia; Ketones; Metronidazole; Piperidines; Plant Bark; Plant Extracts; Plant Leaves; Plant Stems; Senna Plant

l-Rhamnose is transformed to (-)-Cassine via a remarkable four step one pot reaction. The Horner-Wadsworth-Emmons [3 + 2]-1,3-dipolar cycloaddition reaction cascade is the pivotal step in this reaction sequence and makes the synthesis highly efficient.

Topics: Cassia; Ketones; Molecular Structure; Piperidines; Stereoisomerism

The PdCl(2)-catalyzed cyclization of amino allylic alcohol 16 gave the cyclized product 17a with excellent diastereoselectivity. The versatility of compound 17a as the building block for synthesizing cis-2,6-disubstituted piperidine alkaloids has been demonstrated by a total synthesis of (-)-cassine (1). [reaction--see text]

Topics: Alkaloids; Cassia; Ketones; Molecular Structure; Piperidines

The leaves of Senna racemosa yielded the piperidine alkaloid cassine and an inositol methyl ether. Antimicrobial screening of the compounds revealed antibacterial activity of cassine with minimum inhibitory concentrations of 2.5 mg/ml for Staphylococcus aureus and Bacillus subtilis and 5.0 mg/ml for Candida albicans.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Aspergillus niger; Bacillus subtilis; Candida albicans; Escherichia coli; Humans; Ketones; Microbial Sensitivity Tests; Piperidines; Plant Extracts; Plant Leaves; Plants, Medicinal; Pseudomonas aeruginosa; Staphylococcus aureus