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Propionibacterium acnes (P. acnes) is a rod-shaped, anaerobic, Gram-positive, opportunistic bacterium, that causes infectious and inflammatory diseases, such as acne vulgaris synovitis-acnes-pustulosis-hyperostosis-osteitis syndrome, sarcoidosis, and prostate cancer. Earlier evidence suggests that essential oils have been used to treat skin diseases and disorders since ancient times. Thus, the present study investigated the anti-microbial activity of 28 essential oils from nine families, including Lamiaceae, Poaceae, Geraniaceae, Myrtaceae, Zingiberaceae, Verbenaceae, Cupressaceae, Asteraceae, and Cyperaceae against P. acnes. The anti-bacterial susceptibility and efficacy of the essential oils were examined using paper disc diffusion, broth micro-dilution, time-kill kinetics and ROS assays. P. acnes was cultured under anaerobic conditions. The kinetic process evaluated the time and dose-dependent effects of essential oils. The alteration in membrane potential and ROS production were measured in terms of mean fluorescence intensity. Consequently, the chemical composition of essential oil was analyzed by GC and GC/MS analysis. Eighteen essential oils inhibited the growth of P. acnes with a clear zone of 5 – 20.33 mm. Eucalyptus , Mentha, Palmarosa, Lemongrass, Citronella , Geranium, Patchouli, Ocimum , and Clarysage possess better antibacterial activity (ZGI: 10.33 ± 2.31 mm - 20.33 ± 4.72 mm). Lippia alba oil showed the minimum inhibitory concentration (MIC) of 0.125% v/v, and the MIC of Mentha, Ocimum , and Patchouli oils ranged from 0.25% to 0.50% v/v. Further, the concentration and time-kill kinetic study indicated that L. alba and O. sanctum oils suppress the growth at MIC till 12 h and at 2 × MIC until 72 h. Moreover, the oils induced ROS production with one fold change at 2 × MIC. In addition, O. sanctum oil altered the membrane integrity with a fold change of 1.0 and 2.0 at MIC and 2 × MIC, respectively, while L. alba oil modified a fold change of 1.0. The essential oils suppressed bacterial growth by inducing ROS and modulating membrane integrity. Therefore, L. alba and O. sanctum essential oils could be used as an alternative to chemicals/drugs for treating microbe-associated acne problems. [Display omitted] • Antimicrobial efficacy of 28 essential oils from 9 different families was investigated. • Lippia alba and Ocimum sanctum oils suppress the growth of Propionibacterium acnes. • L. alba and O. sanctum oils depict low MIC compared to other essential oils. • L. alba and O. sanctum oils induce ROS production and modulate membrane integrity. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus (SA), is a major human pathogen causing wide range of clinical infections, which has been further complicated by drug resistance like methicillin resistant S. aureus (MRSA), vancomycin intermediate S. aureus (VISA)/vancomycin resistant S. aureus (VRSA), etc. The present study was aimed at determining anti-staphylococcal potential of citral against drug resistant clinical isolates alone and in combination with antibiotics.Purpose: To assess the potential of citral in combination with norfloxacin in treating drug resistant infections of SA.Study Design: In the present study, synergistic interaction of citral and norfloxacin against drug resistant SA strains was evaluated. Further the efficacy and possible mechanism of action of the combination was also evaluated using in vitro and in vivo assays.Method: The anti-staphylococcal activity of each of the monoterpene and the antibiotic was determined in terms of MIC and the effective concentration of both compounds in combination was obtained by checkerboard assay. In vivo efficacy and oral acute toxicity was evaluated in Swiss albino mice model. To understand the mechanism of action, time-kill curve, bacteriolysis, leakage, membrane depolarization, salt tolerance and ethidium bromide efflux assays were performed.Results: Citral was found effective against clinical isolates of SA with MIC values ranging from 75 to 150 µg ml-1 exhibiting bacteriostatic activity. Citral interacted synergistically, reducing MIC of norfloxacin up to 32-folds with FICI ≤ 0.50. Citral did not affect cell wall, but could damage cell membrane, inhibit efflux pump and affect the membrane potential. Citral could reduce the staphylococcal load of spleen and liver tissues in a dose-dependent manner which was further reduced when used in combination with norfloxacin. Citral did not exhibit any mortality or morbidity up to 500 mg kg-1 body weight and found to prolong the post-antibiotic effect of norfloxacin.Conclusion: Based on these observations, citral could be a lead candidate phytomolecule for further developing it into an anti-staphylococcal agent. The observations of combination study will help in reducing the burden of antibiotics leading to delayed resistance development. [ABSTRACT FROM AUTHOR]

The genus Cuscuta belonging to the Cuscutaceae family comprises of about 100–170 species spread around the world. Although several species have been studied for their phytochemical characterization and biological activities but still many species are yet unexplored till date. Cuscuta are parasitic plants generally of yellow, orange, red or rarely green color. The Cuscuta species were reported rich in flavonoid and glycosidic constituents along with alkaloids, fatty acids, fixed oil, minerals, essential oil and others phytomolecules also etc. Flavonoids and other molecules of Cuscuta species were reported for different types of biological activities such as antiproliferative activity, antioxidant activity, anti-inflammatory, hepatoprotective, antimicrobial and anxiolytic activity, while some other flavonoids have exhibited potential antiviral and anticancer especially in ovarian and breast cancer activities. This review is an attempt to compile all the available data for the 24 different of Cuscuta species on the basis of different types of phytochemical constituents and biological studies as above. [ABSTRACT FROM AUTHOR]

Aging is an unavoidable phenomenon, often afflicting structure and functionality of body, marked with onset of age associated manifestations. Parkinson's disease (PD), the second most common form of dementia is manifested with Lewy body formation and dopaminergic dysfunction. Present study explores silymarin, a known hepatoprotective regimen for its efficacy in Aging and PD using Caenorhabditis elegans . Silymarin positively modulated longevity, reduced oxidative stress, independent of feeding behaviour. Up-regulation of longevity and stress related genes daf-16, sod-3, gst-4 and skn-1 indicate the possible involvement of these genes for regulating longevity. In-addition silymarin alleviated PD symptoms by reducing α-synuclein levels, lipid accumulation and enhanced dopamine function. Silymarin executes its beneficial effects through mitigation of free radicals, while achieving alleviation in Parkinsonism possibly through pdr-1 mediated recruitment of ubiquitin proteasome system as evident from qPCR studies. Altogether, silymarin emerged as a potent molecule for investigation in Aging and age related disorders. [ABSTRACT FROM AUTHOR]

Abstract: The 1mm long Caenorhabditis elegans is one of the prime research tools to study different human neurodegenerative diseases. We have considered the case in which increase in the surrounding temperature of this multicellular model leads to abnormal bursts of neuronal cells that can be linked to seizure or convulsion. The induction of such seizure/convulsion mechanism was done by gradually increasing the temperature with 1× buffer (100mM NaCl, 50mM MgCl2) in adult C. elegans. In the present experiment it is demonstrated that Baccoside A can significantly reduce the seizure/convulsion in C. elegans at higher temperatures (26–28±1°C). Furthermore, in T-type Ca2+ channel cca-1 mutant worms, no convulsion was recorded. Our experimental results suggest that plant molecules from Bacopa monnieri may be useful in suppressing the seizure/convulsion in worms. [ABSTRACT FROM AUTHOR]

Abstract: The paper reports an improved pilot scale process technology for the extraction of Cliv-92: a combination of three hepatoprotective coumarinolignoids, cleomiscosins A, B and C from the seeds of Cleome viscosa. The method involved the extraction of the defatted seeds with methanol, which on concentration gave a viscous residue. Trituration of the residue with methanol and keeping it at a low temperature resulted in the precipitation of Cliv-92 which was separated by filtration. Almost half of total yield of Cliv-92 was obtained from the methanolic extract simply by the trituration method. The filtrate obtained was concentrated and adsorbed on celite. The adsorbed material was then partitioned with toluene, ethyl acetate and methanol successively. The fractions obtained from partitioning methods were concentrated and Cliv-92 was isolated from the above fractions by passing through a bed of silica gel. The novelty of the improved process included application of an extrusion device to expel out the fixed oil before extraction, adopting trituration technique to effectively crystallize the coumarinolignoids and using solid-matrix partitioning technique thereby avoiding the use of water for partitioning to isolate the coumarinolignoids. The yield of Cliv-92 obtained was 1.13% carried out at a scale of 100kg/batch level which was about 10 times higher in comparison to previous bench scale process. [Copyright &y& Elsevier]

Abstract: Natural nevirapine (1), a dipyridodiazepinone metabolite has been isolated as a minor constituent with a yield of 0.00397% from the ethyl acetate extract during large scale extraction of Cliv-92 at a level of 100kg/batch from the seeds of Cleome viscosa. Column chromatographic purification of the ethyl acetate extract afforded the molecule which was characterized as nevirapine through spectral analysis and confirmed by single crystal X-ray crystallography. The molecule also has been re-isolated from the same batch of seeds to confirm its presence in the seeds of C. viscosa. The molecule nevirapine has been fully characterized by co-TLC, prep-TLC-MS/MS and chiral HPLC analysis. Isotope Ratio Mass Spectrometric (IRMS) analysis of natural nevirapine and the synthetic drug revealed it to be different. It is an interesting discovery to find out that the natural nevirapine exists as an endogenous metabolite of the plant. This paper also reports the isolation of salicylic acid from the same batch of seeds which afforded nevirapine which may have been due to some plant–pathogenic interaction. [Copyright &y& Elsevier]

Abstract: Large scale extraction of the fruits of Garcinia indica was conducted with water extracted hydroxyl citric acid. The marc left after water extraction was extracted exhaustively with methanol and concentrated methanol. The concentrated methanol extract was adsorbed with celite and dried. The dried celite containing the methanol extract was successively extracted with hexane, chloroform and ethyl acetate to get hexane, chloroform and ethyl acetate extract respectively. Column chromatographic separation of hexane extract afforded two new molecules, one polyisoprenylated benzophenone and a new acylphloroglucinol derivative and two known molecule garcinol and isogarcinol. Likewise, chromatographic separation of the chloroform and ethyl acetate extract also yielded extra quantity of garcinol and isogarcinol respectively. Garcinol was isolated as a major compound among all the four molecules isolated from the fruits G. indica. [Copyright &y& Elsevier]

Abstract: The optically active nevirapine, a natural analogue of the previously designed and synthesized optically inactive nevirapine, a non-nucleoside inhibitor of HIV-1 reverse transcriptase, has been isolated and fully characterized from the seeds of Cleome viscosa. The structure of natural nevirapine has been confirmed by X-ray crystallography. It is an interesting discovery to find out that optically inactive nevirapine was designed and synthesized before the isolation of optically active nevirapine from the seeds of C.viscosa. [Copyright &y& Elsevier]

Highlights • Treatment of palmarosa and ajwain oils inhibited sprouting of potato tubers. • Treatments of lemon grass and clove oils induced sprouting of potato tubers. • Selected oils treatments modulated accumulation of reducing sugars and ethylene. • Selected oils treatments modulated expression of key genes of tuber-sprouting. • Selected oils can be used for reducing post-harvest losses of potato crop. Abstract Use of harmful chemicals and expensive maintenance of cold-storage conditions for controlling sprouting are among the major problems in potato storage. Here, 20 essential oils (EOs) were tested for their sprouting-inhibiting and sprouting-inducing activities. Overall, treatments of lemon grass (LG) and clove (CL) oils could induce sprouting whereas palmarosa (PR) and ajwain (AZ) oils could inhibit sprouting of potato tubers at normal-room-temperature (25 ± 2 °C) storage. Selected-EOs treatments affected sprouting by modulation of accumulation of reducing sugars, ethylene, and expression of genes involved in tuber-sprouting such as ARF , ARP , AIP and ERF. Surprisingly, 7-days AZ-treatments could inhibit sprouting for 30-days which was mediated via damaging apical meristem. However, LG- and CL-treated tubers could produce enhanced potato yield as well. Present work clearly demonstrates that selected-EOs can be used as a promising eco-friendly approach for inducing/inhibiting sprouting of potato tubers during potato storage and those enhancing sprouting can be used for enhancing productivity. [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Tejovati (Zanthoxylum armatum DC; Family- Rutaceae) popularly known as toothache tree is widely distributed in sub-tropical Himalaya region. Traditionally, The Southeast Asian population of Indo-Nepal origin uses it to treat asthma, gout, pain, and inflammation. The Ayurvedic action of the plant includes the balancing of Vata-Kapha in the body. Which lead to various ailments related to the circulation of blood and water, digestion, immunity, and skin. Therefore, in-vitro xanthine oxidase (XO) inhibition potential of the extract could be worth to explore prospect in the prevention/treatment of gouty affections of the joints and other diseases. Aim of study Anti-inflammatory and antioxidant potential of Z. armatum fruit (ZAF) has been reported. To date, no scientific study to validate the claim for gout treatment/management has been attempted so far. The present study deals with the xanthine oxidase inhibitory potential of a various extract of ZAF and marker-based high-performance liquid chromatography (HPLC) standardization of most active fraction. Materials and methods Liquid-liquid partioning of crude methanol extract of the ZAF followed by repeated column chromatography of most active fraction has resulted in the isolation of seven compounds. Five distinct groups of compounds were isolated, purified, and identified. We have investigated the therapeutic action of ZAF in the management of gout through in-vitro assay of XO, a key enzyme involved in gout pathogenesis. Results Phytochemical investigation of ZAF has resulted in the isolation of seven compounds of diverse nature. It is noteworthy to mention that out of seven, five compounds have shown the xanthine oxidase inhibitory action. The ethyl acetate fraction was most potent to inhibit XO. The XO inhibitory activity (IC 50 values) of isolated marker chemical was ranging from 5.62 to 41.21 µM. Three compounds viz. acetyl phenyl acetate (ZA-2), prudomestin (ZA-6), and tambulin (ZA-7) showed the most potent XO inhibitory activity (IC 50 ≈ 6 µM) comparable with a positive control (Allopurinol, IC 50 , 3.38 µM). This is the first validated HPLC-PDA method for simultaneous analysis and accurate quantification of seven compounds (phenolic acid, acetyl phenyl acetate, xylopyranoside, diphenyl ether and three flavones) in ZAF as well as their distribution in other tissues of the plant. Conclusion Most potent three chemicals (ZA-2, 6 and 7) could be considered as bioactive to ensure the robust quality of the enriched fraction of ZAF with defined XO inhibition potential. Therefore, either single purified component or their enriched fraction could be a better choice for the management of gout than the crude extract of ZAF. Developed HPLC method is suitable for quality assurance analysis and process control of ZAF derived product intended for gout management. XO inhibitory potential exhibited by the characterized compounds validate the traditional use of this ZAF for the treatment of gout. Further, a detailed study is required to assess the effect of ZAF chemicals on serum uric acid and mechanism of XO inhibition. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

To create your abstract, type over the instructions in the template box below. Fonts or abstract dimensions should not be changed or altered. [Display omitted] Braylin (10b) is a 8,8-dimethyl chromenocoumarin present in the plants of the family Rutaceae and Meliaceae and possesses vasorelaxing and anti-inflammatory activities. In this study, six 6-alkoxy (10b , 15 – 19), and twelve 6-hydroxy-alkyl amine (20a - 20l) derivatives of braylin (11 and 12) were synthesized to delineate its structural requirement for vasorelaxing activity. The synthesized compounds were evaluated for vasorelaxation response in preconstricted intact rat Main Mesenteric Artery (MMA). The compounds showed l -type VDCC channel blockade depended and endothelium-independent vasorelaxation within the range of Emax < 50.00–96.70 % at 30 µM. Amongst all, 6-alkoxy derivatives were more active than 6-hydroxy-alkyl amine derivatives. The structural refinements about braylin showed that deletion of its methoxy group or homologation beyond ethoxy group presented deleterious effect on vasorelaxation response of braylin. Interestingly, substituting the ethoxy group in 10b presented the best activity and selectivity towards l -type VDCC channel blockade, a specific target cardiovascular function. [ABSTRACT FROM AUTHOR]

Zanthoxylum armatum or Timoor has been used in different traditional system of medicine due to its aromatic properties and also in the treatment of cancer, diarrhea and cholera. In the present investigation, four chemically distinct compounds namely Tambulin (6), Prudomestin (7), Ombuin (8) and 3, 4, 5, 3′, 4′, 5′-hexahydroxydiphenyl ether (9) have been isolated and quantified from the fruits. To explore the biological activities, we have further studied the antiproliferative, antimicrobial and antioxidant efficacy. Tambulin which was also found in maximum amount (0.125%) in fruits revealed significant antiproliferative activity (IC 50 37.96 ± 0.36 to 48.7 ± 0.21 μg/mL) against breast, liver, colon and skin cancer cell lines corroborated by resilient binding interaction with SDH (−6.76 Kcal/mol) and inhibition constant (Ki: 11.02 μM). Hexane and ethyl acetate fraction exhibited moderate antibacterial efficacy (MIC: 250–1000 μg/mL) against selected pathogenic microbes while Ombuin displayed broad spectrum antibacterial effect with MIC ranges from 125 to 500 μg/mL. Total phenolic content (5.27 ± 0.06 to 46.12 ± 0.40 mg/g of gallic acid equivalents), total flavonoids content (6.05 ± 0.24 to 14.46 ± 0.73 mg/g of quercetin equivalents), ferric reducing power (42.35 ± 0.85 to 62.52 ± 0.66 mg/g of ferrous sulfate equivalents) and percent free radical scavenging activity (59.56 ± 0.38 to 64.85 ± 1.78) were also estimated. Our findings infer that Tambulin exhibited significant antiproliferative activity whereas Ombuin was found to display broad spectrum antibacterial activity which adds one more positive attribute to its traditional usage. [ABSTRACT FROM AUTHOR]

Different alkyl amide ( 15a – l ) and alkyl amine ( 16a – e ) derivatives of 7,8-dimethoxy-3-hydroxy-2-(4-methoxyphenyl)benzopyran-4-one were synthesized and evaluated for their anticancer activity against five different cancer cell lines using SRB assay. Compounds 15e , 15i , 15j and 16a – e showed significant anticancer activity within the range of IC 50 2.58–34.86 μM. The most promising molecule, 1 6c , was further analyzed for its effect on cell cycle and apoptosis of estrogen receptor positive cancer cells (MCF-7 cells) which showed that 16c triggered apoptosis in MCF-7 cells and arrested cells population at sub-G 0 (apoptotic) and G 2 M phase. In tubulin polymerization assay, 16c interfered with kinetics of tubulin polymerization. [ABSTRACT FROM AUTHOR]

[Display omitted] • Marigold petals are the primary industrial source of lutein. • An efficient green process described for isolating high purity lutein from marigold petals. • The process does not require recrystallization for further purification of free lutein. • The process does not use toxic solvents, high temperatures, acid, etc. • 2-MeTHF appears as a potential alternative solvent to hexane for lutein extraction. Marigold (Tagetes erecta L.) petals are the primary industrial source of lutein, which is used as a colouring agent and nutrient supplement to foods. This research extracted marigold petals using different solvents, covering conventional and non-toxic green solvents. The oleoresin, free lutein, and recrystallized lutein yields varied from 8.47–16.67%, 2.56–9.62%, and 1.11–1.61%, respectively. The purity of lutein was achieved up to 92.57% and 97.64% in conventional and newly established green methods, respectively. The present study described an efficient green process to isolate lutein with significantly improved yield (2.56%) and purity (97.33%) over the conventional methods. Based on the results, 2-methyltetrahydrofuran could be a practical green alternative to the traditional toxic solvents for the processing of lutein. Further, the chemical analysis of the essential oil of the residual receptacles obtained after removing petals revealed the presence of important organic volatiles, including piperitone (54.7%) and piperitenone oxide (6.5%), indicating its usefulness for value-addition. [ABSTRACT FROM AUTHOR]

Rose-scented geranium (Pelargonium graveolens L'Herit. ex Aiton), belonging to the family Geraniaceae, has gained considerable attention because of its fragrance and high economic value. The compositional complexity of rose-scented geranium essential oil (GEO) has been challenging for quality control. In this study, the chemical profiles of GEOs extracted from Indian cultivars/genotypes were developed using polarity-based fractionation, followed by characterization using a combination of gas chromatography (GC-FID), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance spectroscopy (NMR). The analysis led to the identification of 121 compounds. Major components of the GEOs were citronellol (22.4–42.2 %), geraniol (5.7–30.5 %), linalool (2.1–9.8 %), citronellyl formate (4.0–9.5 %), isomenthone (5.3–7.5 %), geranyl formate (2.0–5.1 %), 6,9-guaiadiene (0.0–4.3 %), 10- epi - γ -eudesmol (0.2–6.4 %), 2-phenyl ethyl tiglate (1.0–2.1 %), geranyl tiglate (1.4–2.7 %), germacrene D (0.8–1.7 %) and geranial (0.4–1.6 %). This study identified effective markers which could help determine the authenticity of Indian cultivars/genotypes. Physical properties and chromatographic profiles of GEOs and terpeneless GEOs (TLOs) derived from Indian cultivar/genotype were compared. The two-step chromatographic separation coupled with principal component analysis allowed the identification of possible markers. The presence or absence of the sesquiterpenes, namely 10- epi - γ -eudesmol, 6,9-guaiadiene, and some other minor constituents, physical, and organoleptic properties, could effectively distinguish and define the quality of Indian cultivars/genotypes. Besides, the GEOs and TLOs prepared from different cultivars exhibited significant antimicrobial activity against Staphylococcus aureus and Candida albicans. [Display omitted] • Rose-scented geranium essential oil is known for its chemical complexity. • Chemical characterization and quality control of Indian genotypes were done. • Fractionation followed by GC-MS analysis led to the separation of co-eluting components. • The compounds identified could be viable tools for genotypes authentication. • Indian genotypes meet international standards. [ABSTRACT FROM AUTHOR]

This paper reports comparative extraction efficiencies and enrichment methods for natural insecticidal compounds pyrethrins from the dried flowers of Chrysanthemum cinerariaefolium using different techniques and solvent systems. Four different extraction techniques viz. percolation, agitation with heat, sonication and soxhlet using five different solvent systems hexane, ethyl acetate, acetone, acetonitrile and methanol were evaluated. In these studies, it was observed that maximum extract yield was obtained using methanol as extracting solvent by soxhlet technique, although the content of total pyrethrins was higher in the hexane extract than in methanol. The successive and maximum enrichment of the total pyrethrins was achieved by solid-matrix partitioning of the extract using acetonitrile as extracting solvent followed by treatment with activated charcoal, subsequent chilling and filtration by which enrichment of total pyrethrins up to 60.37% content was obtained. The quantitative analysis of the extraction and enrichment development protocol was validated by a simple, accurate, reproducible RP-HPLC-UV method using a binary gradient elution comprising of acetonitrile and water. The separation was achieved on a Waters-symmetry C 18 column (150 mm × 3.9 mm i.d., 5 μm) that achieved a greater degree of linearity within an overall concentration range of 5–500 μg mL −1 and higher degree of correlation (0.9842 ≤ r 2 ≤ 0.9987) for all the pyrethrin esters. [ABSTRACT FROM AUTHOR]

Highlights: [•] Isolation of new compounds from the roots of Oenothera biennis. [•] Two new compounds identified as dihydroxyprenyl xanthone acetylated and cetoleilyl diglucoside. [•] Study of antioxidant activities of new and previously isolated compounds. [•] The compounds were investigated for the antioxidant effects using several different methods. [ABSTRACT FROM AUTHOR]

4-chloro eugenol (4CE), a semisynthetic analog of phytomolecule eugenol exhibited potent antiplasmodial activity with IC 50 in the range of 1.5–5 μM against sensitive as well as drug resistant strain of P. falciparum. This analog also showed synergy with a clinically used antimalarial drug artesunate and was able to curtail the IC 50 of artesunate up to 4–5 folds. Although, 4CE did not show any effect on heme polymerization, the most common drug target in the malaria parasite, it could increase the level of reactive oxygen species (ROS) and reactive nitrogen species (RNS) alone as well as in combination with artesunate. Further, 4CE induced oxidative stress was observed to affect the macromolecules in terms of DNA damage, protein carbonylation and lipid peroxidation. At the physiological level, cellular organelles like mitochondria and endoplasmic reticulum were observed to be get affected by 4CE in terms of membrane depolarization and calcium ion leakage respectively. These observations could be validated by expression analysis of oxidative stress responsive genes and proteins. Further, in in vivo assay, 4CE showed significant chemo-suppression of parasitemia as well as an increase in mean survival time in the murine malaria model. Interestingly, in combination with artesunate, 4CE showed higher chemo-suppression as well as enhanced mean survival time at a much lower concentrations of both the partners as compared to an individual dose of artesunate and 4CE. A combination of 4CE and artesunate was also observed to attenuate cerebral malaria pathogenesis. [ABSTRACT FROM AUTHOR]

A series of substituted 8,8-dimethyl-8 H -pyrano[2,3- f ]chromen-2-ones (chromeno-coumarin hybrids) was synthesized from scopoletin (11) as vasorelaxing agents. The synthesized compounds 21a-f, 22, 23a-e and scopoletin (11) were evaluated for vasorelaxation in endothelium intact rat main mesenteric artery (MMA). Compounds 11 , 21a , 21c - f and 22 showed significant vasorelaxation in precontracted MMA within the range of EC 50 value 1.58–5.02 µM. These derivatives presented 29.40–70.89 fold increased sensitivity for experimental tissue compared to scopoletin (11), the parent molecule. Among others, 22 was found to be the most active compound which had EC 50 1.58 µM with 70.89 fold increased sensitivity. The mechanistic evaluation of 22 showed that it exerted vasorelaxation through Ca2+-activated K+ (BKca) channel and the effect was endothelium-independent. [ABSTRACT FROM AUTHOR]