Phytochemical study of Magonia pubescens A. St.-Hil. and cytotoxicity of branches aqueous extract on breast cancer and leukemia cells.

Magonia pubescens is a natural species from the Brazilian cerrado biome. Its fruits and seeds are used in the treatment of seborrheic dermatitis, a common inflammatory skin disease. In this work, the known compounds lapachol, stigmasterol, maniladiol and scopoletin were isolated from hexane and dichloromethane extracts of M. pubescens branches. The aqueous extract of this material was fractioned through a liquid-liquid partition and the obtained fractions were analyzed by UHPLC-MS/MS. The results obtained were compared with data from three databases, leading to the putative identification of 51 compounds from different classes, including flavonoids, saponins and triterpenes. The cytotoxicity of aqueous fractions was assayed against breast cancer (MDA-MB-231) and leukemia (THP-1 and K562) cells. The best activity was observed for fraction AE3 against MDA-MB-231 cells (IC50 30.72 µg.mL-1).

Consensus on functional assessment of chronic pain in primary care: a Delphi study.

BACKGROUND: Chronic pain is a public health concern affecting 20-30% of the population of Western countries. Focus groups of people with persistent pain indicated that their overall physical function had deteriorated because of pain, therefore assessment of function should be an integral part of pain assessment. The objective of this study was to establish a consensus on assessment of function in chronic pain primary care patients and to evaluate the use of scales and clinical guidelines in clinical practice. METHODS: A Delphi study (CL4VE study) was carried out. A group of primary care physicians, were asked to rate how strongly they agreed/disagreed with the statements in: general functioning data, and functioning outcomes in chronic pain patients. RESULTS: Seventy-one primary care physicians were invited to participate. Of these, 69 completed Round 1 (98.5% response rate), and 68 completed Round 2 (97.1%). Under the predefined criterion, a high degree of agreement (91.4%) was observed, this was confirmed in 32 of 35 questions in the second round. Discrepancies were noted, firstly, because functioning was only linked to joint recovery; secondly, in the use of specific scales and questionnaires to measure functioning, and thirdly, that no scale of functioning is used in clinical practice due to complexity and lack of time for assessment. CONCLUSIONS: Physicians agreed on the need for a precise definition of the concept of patient functional impediment to facilitate homogeneous recognition, and for the development of simple and practical scales focused on patients with chronic pain and their needs.

Epimers l- and d-Phenylseptin: How the relative stereochemistry affects the peptide-membrane interactions.

In recent decades, several epimers of peptides containing d-amino acids have been identified in antimicrobial sequences, a feature which has been associated with post-translational modification. Generally, d-isomers present similar or inferior antimicrobial activity, only surpassing their epimers in resistance to peptidases. The naturally occurring l-Phenylseptin (l-Phes) and d-Phenylseptin (d-Phes) peptides (FFFDTLKNLAGKVIGALT-nh2) were reported with d-epimer showing higher activity against Staphylococcus aureus and Xanthomonas axonopodis in comparison with the l-epimer. In this study, we combine structural (CD, solution NMR), orientational (solid-state NMR) and biophysical (ITC, DSC and DLS) studies to understand the role of the d-phenylalanine in the increase of the antimicrobial activity. Although both peptides are structurally similar in the helical region ranging from D4 to the C-terminus, significant structural differences were observed near the peptides' N-termini (which encompasses the FFF motif). Specific aromatic interactions involving the phenylalanine side chains of d-Phes is responsible to maintaining the F1-F3 residues on the hydrophobic face of the peptide, increasing its amphipathicity when compared to the l-epimer. The higher capability of d-Phes to exert an efficient anchoring in the hydrophobic core of the phospholipid bilayer indicates a pivotal role of the N-terminus in enhancing the interaction between the d-peptide and the membrane interface in relation to its epimer.

Chemical Composition of Magonia pubescens Essential Oils and Gamma-Radiation Effects on Its Constituents and Cytotoxic Activity in Leukemia and Breast Cancer Model.

Magonia pubescens A. St.-Hil. is a Brazilian species often used in ethnopharmacology for wound and pain healing and seborrhea treatment. For the first time, essential oils (EOs) obtained from M. pubescens inflorescences were studied. The plant materials (Montes Claros, Brazil, 2018) were submitted to different gamma-radiation doses and their chemical compositions were analyzed by GC/MS and GC-FID. The cytotoxic activity of the EOs was evaluated against K562 and MDA-MB-231 cancer cell lines. A total of 30 components were identified, being 24 compounds detected for the first time in M. pubescens. The main obtained components were hotrienol (35.9 %), cis-linalool oxide (17.0 %) and trans-linalool oxide (10.2 %). The chemical composition of the EO was slightly affected by the applied radiation doses. Irradiated and non-irradiated EOs showed cytotoxic activity against both cell lines and the non-irradiated EO sample was the most active against the K562 cell lines (IC50 =22.10±1.98).

Anti-inflammatory and cytotoxic activities of the extracts, fractions, and chemical constituents isolated from Luehea ochrophylla Mart.

BACKGROUND: Stem bark of Luehea ochrophylla (L. ochrophylla) is used by the traditional Brazilian medicine for treatment of rheumatic diseases and tumors. This study aimed to investigate inhibition of acute and chronic inflammations and cytotoxic activity of extracts, fractions, and isolated compounds from L. ochrophylla. METHODS: Hexane (HE) and ethanol (EE) extracts obtained from stem bark of L. ochrophylla were submitted to chromatographic fractionation. In order to test acute inflammation, experimental model of impact injury was used, followed by transdermal application of gels using phonophoresis. Histological analysis was based on scores assigned by the capacity of decreasing the lesion. To evaluate the effect EE and fractions on cell proliferation, human lymphocytes were stimulated with phytohemagglutinin and analyzed using flow cytometry. Proliferation was measured using VPD 450 staining and the calculated proliferative index (PI). The cytotoxic activity was evaluated using MTT colorimetric method against MDA-MB-231, MCF-7, HCT-116, and Vero cells. GraphPad Prism Version 5 was used for statistical analysis. RESULTS: HE and EE provided friedelin, ß-friedelinol, lupeol, mixture of lupeol and pseudotaraxasterol, ß-sitosterol, betulinic acid, mixture of lupeol and taraxasterol, (-)-epicatechin, ß-sitosterol-3-O-ß-D-glucopyranoside, and (+)-epicatechin-(4ß-8)-epicatechin. HE, ethyl acetate fraction (AF), betulinic acid, and ß-sitosterol promoted regeneration of muscle fibers caused by muscle injury. AF significantly (p < 0.05) reduced the lymphocyte proliferation index (1.36 for cultures stimulated with PHA, 0.7 for untreated cultures and 0.12 for cultures stimulated with PHA and treated with AF 25 µg/mL and AF 50 µg/mL, respectively). ß-Sitosterol-3-O-ß-D-glucopyranoside exhibited high cytotoxic activity (IC50 = 1.279 µg/mL) against HCT-116 cell line. CONCLUSION: These results suggest that extracts, fractions, and chemical constituents from L. ochrophylla decreases inflammatory processes generated by muscle injury. The anti-inflammatory activity may be justified by high inhibition of T cell proliferation. These extracts, fractions, and chemical constituents from L. ochrophylla may be useful as a therapeutic agent against rheumatic diseases. Moreover, chemical constituents from L. ochrophylla show potent cytotoxic activity against colon and rectal carcinomas.

[Cost-effectiveness model of a fixed dose combination of solifenacin and tamsulosin for the treatment of LUTS associated with BPH with inadequate response to monotherapy.] / Modelo de coste­efectividad de la combinación a dosis fijas de solifenacina y tamsulosina en el tratamiento de los STUI asociados a HBP con respuesta inadecuada a la monoterapia.

OBJECTIVE: To compare the cost-effectiveness of fixed dose combination of solifenacin 6 mg and tamsulosin 0.4 mg in a controlled absorption system (TOCAS) with free dose combination of tolterodine plus tamsulosin, when used for the treatment of patients with moderate to severe lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) who do not respond adequately to monotherapy. The analysis was conducted from the perspective of the Spanish National Health System. METHODS: A Markov model was developed in Excel, with 1-year time horizon. The transition probabilities of the model were obtained from the NEPTUNE clinical trial and published literature. Unit costs were obtained from Spanish sources. The use of healthcare resources was validated by Spanish clinical experts. Both deterministic and probabilistic analyses were performed to determine the key drivers of the model. RESULTS: Treatment with fixed dose combination of solifenacin plus TOCAS was found to be dominant, as it resulted in lower annual costs (€ 1,349 vs. € 1,619) and greater quality-adjusted life years (QALY) gained per patient (0.8406 vs. 0.8386) when compared with free dose combination of tolterodine plus tamsulosin. According to the probabilistic analyses, the probability of the fixed dose combination treatment being cost-effective at a willingness to pay threshold of € 20,000 or 30,000 would be 100%. CONCLUSIONS: This analysis suggests that fixed dose combination of solifenacin plus TOCAS represents a cost-effective choice for the treatment of patients with moderate to severe LUTS/BHP, compared to free dose combination of tolterodine plus tamsulosin.

Modelo de coste-efectividad de la combinación a dosis fijas de solifenacina y tamsulosina en el tratamiento de los STUI asociados a HBP con respuesta inadecuada a la monoterapia / Cost-effectiveness model of a fixed dose combination of solifenacin and tamsulosin for the treatment of LUTS associated with BPH with inadequate response to monotherapy

OBJETIVO: Evaluar el coste-efectividad de la combinación a dosis fijas de 6 mg de solifenacina y 0,4 mg de tamsulosina en un sistema oral de absorción controlada (TOCAS) en el tratamiento de los pacientes con síntomas del tracto urinario inferior (STUI) moderados a graves asociados a la hiperplasia benigna de próstata (HBP) (STUI/HBP) y una respuesta inadecuada a la monoterapia, en comparación con el tratamiento de tolterodina más tamsulosina, desde la perspectiva del Sistema Nacional de Salud (SNS). MÉTODOS: Se realizó un modelo de Markov en Excel con un horizonte temporal de 1 año. Las probabilidades de transición del modelo se obtuvieron del ensayo clínico NEPTUNE y la literatura. Los costes unitarios se obtuvieron de fuentes españolas. El uso de recursos sanitarios fue validado por expertos clínicos españoles. Se realizaron análisis determinísticos y probabilísticos. RESULTADOS: El tratamiento con la combinación a dosis fijas de solifenacina más TOCAS dio lugar a un menor coste anual (1.349 Euros vs. 1.619 Euros) y un aumento de años de vida ajustados por su calidad (AVAC) (0,8406 vs. 0,8386) por paciente en comparación con tolterodina más tamsulosina, siendo por tanto dominante. La probabilidad de que el tratamiento a dosis fijas de solifenacina más TOCAS sea coste-efectivo frente al tratamiento con tolterodina más tamsulosina sería del 100% para una disponibilidad a pagar de 20.000-30.000 Euros por AVAC ganado. CONCLUSIONES: El tratamiento con dosis fijas de solifenacina más TOCAS en pacientes con STUI/HBP moderados a graves daría lugar a una ganancia de AVAC, siendo una estrategia coste-efectiva y dominante frente al tratamiento con tolterodina más tamsulosina

OBJECTIVE: To compare the cost-effectiveness of fixed dose combination of solifenacin 6 mg and tamsulosin 0.4 mg in a controlled absorption system (TOCAS) with free dose combination of tolterodine plus tamsulosin, when used for the treatment of patients with moderate to severe lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) who do not respond adequately to monotherapy. The analysis was conducted from the perspective of the Spanish National Health System. METHODS: A Markov model was developed in Excel, with 1-year time horizon. The transition probabilities of the model were obtained from the NEPTUNE clinical trial and published literature. Unit costs were obtained from Spanish sources. The use of healthcare resources was validated by Spanish clinical experts. Both deterministic and probabilistic analyses were performed to determine the key drivers of the model. RESULTS: Treatment with fixed dose combination of solifenacin plus TOCAS was found to be dominant, as it resulted in lower annual costs (Euros 1,349 vs. Euros 1,619) and greater quality-adjusted life years (QALY) gained per patient (0.8406 vs. 0.8386) when compared with free dose combination of tolterodine plus tamsulosin. According to the probabilistic analyses, the probability of the fixed dose combination treatment being cost-effective at a willingness to pay threshold of Euros 20,000 or 30,000 would be 100%. CONCLUSIONS: This analysis suggests that fixed dose combination of solifenacin plus TOCAS represents a cost-effective choice for the treatment of patients with moderate to severe LUTS/BHP, compared to free dose combination of tolterodine plus tamsulosin

On the autorotation of animal wings.

Botanical samaras spin about their centre of mass and create vertical aerodynamic forces which slow their rate of descent. Descending autorotation of animal wings, however, has never been documented. We report here that isolated wings from Anna's hummingbirds, and also from 10 species of insects, can stably autorotate and achieve descent speeds and aerodynamic performance comparable to those of samaras. A hummingbird wing loaded at its base with the equivalent of 50% of the bird's body mass descended only twice as fast as an unloaded wing, and rotated at frequencies similar to those of the wings in flapping flight. We found that even entire dead insects could stably autorotate depending on their wing postures. Feather removal trials showed no effect on descent velocity when the secondary feathers were removed from hummingbird wings. By contrast, partial removal of wing primaries substantially improved performance, except when only the outer primary was present. A scaling law for the aerodynamic performance of autorotating wings is well supported if the wing aspect ratio and the relative position of the spinning axis from the wing base are included. Autorotation is a useful and practical method that can be used to explore the aerodynamics of wing design.

Effects of Red Blood Cell Transfusion on Long-Term Disability of Patients with Traumatic Brain Injury.

BACKGROUND: This 3-year prospective study examined the association between red blood cell transfusion (RBCT) and 1-year neurocognitive and disability levels in 309 patients with traumatic brain injury (TBI) admitted to the neurological intensive care unit (NICU). METHODS: Using a telephone interview-based survey, functional outcomes were assessed by the Glasgow Outcome Scale (GOS), Rancho Los Amigos Levels of Cognitive Functioning Scale (RLCFS), and Disability Rating Scale (DRS) and dichotomized as favorable and unfavorable (dependent variable). The adjusted influence of RBCT on unfavorable results was assessed by conventional logistic regression, controlling for illness severity and propensity score (introduced as a continuous variable and by propensity score-matched patients). RESULTS: Overall, 164 (53 %) patients received ≥1 unit of RBCT during their NICU stay. One year postinjury, transfused patients exhibited significantly higher unfavorable GOS (46.0 vs. 22.0 %), RLCFS (37.4 vs. 15.4 %), and DRS (39.6 vs. 18.7 %) scores than nontransfused patients. Although transfused patients were more severely ill upon admission, their adjusted odds ratios (95 % confidence intervals) for unfavorable GOS, RLCFS, and DRS scores were 2.5 (1.2-5.1), 3.0 (1.4-6.3), and 2.3 (1.1-4.8), respectively. These odds ratios remained largely unmodified when the calculated propensity score was incorporated as an independent continuous variable into the multivariate analysis. Furthermore, in 76 pairs of propensity score-matched patients, the rate of an unfavorable RLCFS score at the 1-year (but not 6-month) follow-up was significantly higher in transfused than nontransfused patients [3.0 (1.1-8.2)]. CONCLUSION: Our results strongly suggest an independent association between RBCT and unfavorable long-term functional outcomes of patients with TBI.

Fibromialgia y trastornos de la conducta alimentaria en la obesidad mórbida / Fibromyalgia and eating disorders in morbid obesity

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Pentacyclic triterpenes and steroids from the stem bark of uchi (Sacoglottis uchi, Humiriaceae) / Triterpenos pentacíclicos e esteróides da casca do uchi (Sacoglottis uchi, Humiriaceae)

The ethanol extract from stem bark of Sacoglottis uchi Huber (popularly known as “uchi” in the Amazon Region) was submitted to chromatographic fractionation. The dichloromethane fractions provided the pentacyclic triterpene 3-oxo-friedelin (1). The dichloromethane:methanol fractions provided the pentacyclic triterpenes pseudotaraxasterol (2), lupeol (3), a-amyrin (4), betulin (5), and methyl 2ß,3ß-dihydroxy-urs-12-en-28-oate (6) and a mixture of the steroids sitosterol (7) and stigmasterol (8). Their chemical structures were determined by NMR spectroscopy and comparison with spectroscopic data from the literature. All compounds are described for the first time in this species.

O extrato etanólico da casca do caule de Sacoglottis uchi Huber (conhecida popularmente como “uchi” na Amazônia) foi submetido a fracionamento cromatográfico. As frações eluídas com diclorometano forneceram o triterpeno pentacíclico 3-oxo-friedelina (1). As frações em diclorometano:metanol forneceram os triterpenos pentacíclicos pseudotaraxasterol (2), lupeol (3), a-amirina (4), betulina (5) e 2ß,3ß-di-hidroxi-urs-12-en-28-oato de metila (6), além de uma mistura dos esteróides sitosterol (7) e estigmasterol (8). Suas estruturas químicas foram determinadas por espectroscopia de RMN e comparação com os dados espectroscópicos descritos na literatura. Todas as substâncias isoladas são descritas pela primeira vez nesta espécie.

Anti-inflammatory effects in muscle injury by transdermal application of gel with Lychnophora pinaster aerial parts using phonophoresis in rats.

BACKGROUND: Lycnophora pinaster is used by the traditional Brazilian medicine for the treatment of inflammations. Anti-inflammatory activity of Lycnophora pinaster was investigated for extracts, fractions, and isolated compounds of their aerial parts. The hexane extract (HE) provided α-amyrin, lupeol, mixture of α-amyrin and lupeol, mixture of 3-O-acetyl-lupeol and 3-O-acetyl-pseudotaraxasterol, and mixture of the steroids stigmasterol and sitosterol. The aqueous extract (WE) provided a fraction containing alkaloids (AF) and another one containing phenolic compounds (PF). METHODS: The crude hexane extract obtained from aerial parts of L. pinaster was submitted to chromatographic fractionation. The fractionation of PF was performed by preparative HPLC analysis, providing the flavonoid quercetin. The extracts, fractions, and compounds isolated from L. pinaster were tested to evaluate the anti-inflammatory activity by experimental model of impact injury, followed by transdermal application of gels with these samples. The application of the gels was performed using phonophoresis in rat paws after induction of muscle injury. Histological analysis was based on scores assigned by the capacity of decreasing the lesion. RESULTS: HE and WE exhibited anti-inflammatory activity. Some fractions, triterpenes, and steroids also reduced the inflammatory infiltrates caused by muscle injury. Lupeol promoted a significant reduction of inflammation. Quercetin also provided significant results, promoting the greatest decreases in muscle injury. CONCLUSION: The results of this work suggest that topical application of triterpenes, steroids and flavonoid significantly decreases the inflammatory process generated by muscle injury. The transdermal application using phonophoresis in rat paws of gel with lupeol and quercetin attenuates the inflammation.

Changes in the essential oil composition of leaves of Echinodorus macrophyllus exposed to

Leaves of Echinodorus macrophyllus (Kunth) Micheli, Alismataceae, were exposed to different doses of γ-radiation (0.00, 1.00, 3.00, 5.00, 10.00, and 20.00 kGy) and the chemical composition of their essential oils was investigated. The extractive process of the essential oil was more favored when the leaves were irradiated. The essential oil components were identified by correlation between GC-FID data and retention parameters obtained from the Kováts method. Moreover, GC-MS analyses of the essential oils were correlated with fragmentation profiles in the NIST standard mass fragmentation data bank. The essential oil of E. macrophyllus contains biologically active constituents of different chemical classes. Acyclic monoterpenes and sesquiterpenes showed increase in concentration when the leaves were exposed to γ-radiation. On the other hand, the component concentrations of some chemical classes were lightly decreased, i.e., for bicyclic monoterpenes, diterpenes, triterpenes, carboxylic esters, and carotenoid derivatives.

New triterpenes from Maytenus robusta: structural elucidation based on NMR experimental data and theoretical calculations.

Leaves of Maytenus robusta (Celastraceae) were subjected to phytochemical investigation mainly directed at the isolation of pentacyclic triterpenes. The compounds friedelin (1), β-friedelinol (2), 3-oxo-21β-H-hop-22(29)-ene (7), 3,4-seco-friedelan-3,11β-olide (8), 3β-hydroxy-21β-H-hop-22(29)-ene (9), 3,4-seco-21β-H-hop-22(29)-en-3-oic acid (10), 3,4-seco-friedelan-3-oic acid (11), and sitosterol were identified in the hexane extract of M. robusta leaves. Compounds 8 and 9 are described herein for the first time. The structure and stereochemistry of both compounds were experimentally established by IR, HRLC-MS, and 1D (1H, 13C, and DEPT 135) and 2D (HSQC, HMBC and COSY) NMR data and supported by correlations with carbon chemical shifts calculated using the DFT method (BLYP/6-31G* level). Compounds 7 and 10 are also described for the first time, and their chemical structures were established by comparison with NMR data of similar structures described in the literature and correlations with BLYP/6-31G* calculated carbon chemical shifts. Compound 9, a mixture of 11 and sitosterol, and 3β,11β-dihydroxyfriedelane (4) were evaluated by the Ellman’s method and all these compounds showed acethylcholinesterase inhibitory properties.

Slim-filter: an interactive Windows-based application for illumina genome analyzer data assessment and manipulation.

BACKGROUND: The emergence of Next Generation Sequencing technologies has made it possible for individual investigators to generate gigabases of sequencing data per week. Effective analysis and manipulation of these data is limited due to large file sizes, so even simple tasks such as data filtration and quality assessment have to be performed in several steps. This requires (potentially problematic) interaction between the investigator and a bioinformatics/computational service provider. Furthermore, such services are often performed using specialized computational facilities. RESULTS: We present a Windows-based application, Slim-Filter designed to interactively examine the statistical properties of sequencing reads produced by Illumina Genome Analyzer and to perform a broad spectrum of data manipulation tasks including: filtration of low quality and low complexity reads; filtration of reads containing undesired subsequences (such as parts of adapters and PCR primers used during the sample and sequencing libraries preparation steps); excluding duplicated reads (while keeping each read's copy number information in a specialized data format); and sorting reads by copy numbers allowing for easy access and manual editing of the resulting files. Slim-Filter is organized as a sequence of windows summarizing the statistical properties of the reads. Each data manipulation step has roll-back abilities, allowing for return to previous steps of the data analysis process. Slim-Filter is written in C++ and is compatible with fasta, fastq, and specialized AS file formats presented in this manuscript. Setup files and a user's manual are available for download at the supplementary web site ( https://www.bioinfo.uh.edu/Slim_Filter/). CONCLUSION: The presented Windows-based application has been developed with the goal of providing individual investigators with integrated sequencing reads analysis, curation, and manipulation capabilities.

Chemical constituents and biological activities of species of Justicia: a review

The Acanthaceae family is an important source of therapeutic drugs, and the ethnopharmacological knowledge of this family requires urgent documentation as several of its species are near extinction. Justicia is the largest genus of Acanthaceae, with approximately 600 species. The present work provides a review addressing the chemistry and pharmacology of the genus Justicia. In addition, the biological activities of compounds isolated from the genus are also covered. The chemical and pharmacological information in the present work may inspire new biomedical applications for the species of Justicia, considering atom economy, the synthesis of environmentally benign products without producing toxic by-products, the use of renewable sources of raw materials, and the search for processes with maximal efficiency of energy.

Evaluation of the bactericidal and trypanocidal activities of triterpenes isolated from the leaves, stems, and flowers of Lychnophora pinaster

The phytochemical investigation on the aereal parts of Lychnophora pinaster Mart., Asteraceae, was carried to isolation of triterpenes. 3-O-Acetyl-lupeol (1), 3-O-acetyl-pseudotaraxasterol (2), and 3-O-acetyl-α-amyrin (3) were isolated from hexanic extract and 4,4-dimethyl-cholesta-22,24-dien-5-ol (4), α-amyrin (5), and lupeol (6) were isolated from hexanic/dichlorometanic extract of the leaves. Compounds Δ7-bauerenyl acetate (7), friedelin (8), stigmasterol (9), and sitosterol (10) were isolated from the hexanic/dichlorometanic extract of the stems. The steroids 9 and 10 were also isolated from the hexanic/dichlorometanic extract of the flowers. Triterpenes 1, 3, 4, and 7 are described for the first time in the genus Lychnophora. The apolar fractions of the leaf and stem extracts and some isolated triterpenes showed low trypanocidal activity. Moreover, apolar fractions of the leaf and stem extracts and 5 showed antibacterial action against Staphylococcus aureus.

Synthesis, antiproliferative activity in cancer cells and theoretical studies of novel 6α,7ß-dihydroxyvouacapan-17ß-oic acid Mannich base derivatives.

Natural products are great prototypes for the design of new anticancer agents. The plant-derived natural product 6α,7ß-dihydroxyvouacapan-17ß-oic acid (1) is promising for the development of more potent antiproliferative agents against human cancer cells. Indeed, its lactone derivative 6α-hydroxyvouacapan-7ß,17ß-lactone (2), a non-natural furanoditerpene, exhibited higher anticancer activity than compound 1. Herein, we describe the synthesis and antiproliferative activity of six new Mannich derivatives of compound 2 against nine cancer cell lines. Overall, our results revealed that Mannich derivatives 3-8 were more potent than compound 2 in inhibiting the proliferation of cancer cells. Theoretical studies also supported our findings, revealing the nucleophilic character of furan ring as an important feature for antiproliferative activity of the studied Mannich derivatives.

13C-NMR data of diterpenes isolated from Aristolochia Species.

The genus Aristolochia,an important source of physiologically active compounds that belong to different chemical classes, is the subject of research in numerous pharmacological and chemical studies. This genus contains a large number of terpenoid compounds, particularly diterpenes. This work presents a compilation of the 13C-NMR data of 57 diterpenoids described between 1981 and 2007 which were isolated from Aristolochia species. The compounds are arranged skeletonwise in each section, according to their structures, i.e., clerodane, labdane, and kaurane derivatives. A brief discussion on the 13C chemical shifts of these diterpenes is also included.