Synthesis, characterization, anti-mycobacterial activity and in silico study of new 2,5-disubstituted-1,3,4-oxadiazole derivatives.

A series of new 2,5-disubstituted-1,3,4-oxadiazole derivatives (5a-j and 6a-j) have been designed and synthesized in four-steps. Sixteen compounds among the twenty compounds are reported for the first time. The compounds were characterized and confirmed by the FTIR, 1D- and 2D-NMR and HRMS analyses, and were tested against Mycobacterium smegmatis and Mycobacterium tuberculosis H37Ra. Compound 5d was the most active against M. smegmatis with MIC value of 25 µM, and exhibited cidal activity with MBC of 68 µM, respectively. The time-kill assay showed the good killing rate at 77% with the combination of isoniazid (INH). In addition, checkboard assay confirmed the interaction of compound 5d was categorised as additive. Docking simulation has been performed to position 5d into the pantothenate synthetase active site with binding free energy value -8.6 kcal mol-1. It also occupied the same active site as that of standard native ligand with similar interactions, which clearly indicate their potential as pantothenate synthetase inhibitor.

Synthesis, characterization, anti-mycobacterial activity and in silico study of new 2,5-disubstituted-1,3,4-oxadiazole derivatives

@#A series of new 2,5-disubstituted-1,3,4-oxadiazole derivatives (5a-j and 6a-j) have been designed and synthesized in four-steps. Sixteen compounds among the twenty compounds are reported for the first time. The compounds were characterized and confirmed by the FTIR, 1D- and 2D-NMR and HRMS analyses, and were tested against Mycobacterium smegmatis and Mycobacterium tuberculosis H37Ra. Compound 5d was the most active against M. smegmatis with MIC value of 25 µM, and exhibited cidal activity with MBC of 68 µM, respectively. The time-kill assay showed the good killing rate at 77% with the combination of isoniazid (INH). In addition, checkboard assay confirmed the interaction of compound 5d was categorised as additive. Docking simulation has been performed to position 5d into the pantothenate synthetase active site with binding free energy value –8.6 kcal mol-1. It also occupied the same active site as that of standard native ligand with similar interactions, which clearly indicate their potential as pantothenate synthetase inhibitor.

Natural DENV-2 NS2B/NS3 protease inhibitors from Myristica cinnamomea King.

The NS2B/NS3 protease is crucial for the pathogenesis of the DENV. Therefore, the inhibition of this protease is considered to be the key strategy for the development of new antiviral drugs. In the present study, malabaricones C (3) and E (4), acylphenols from the fruits of Myristica cinnamomea King, have been respectively identified as moderate (27.33 ± 5.45 µM) and potent (7.55 ± 1.64 µM) DENV-2 NS2B/NS3 protease inhibitors, thus making this the first report on the DENV-2 NS2B/NS3 protease inhibitory activity of acylphenols. Based on the molecular docking studies, compounds 3 and 4 both have π-π interactions with Tyr161. While compound 3 has hydrogen bonding interactions with Gly151, Gly153 and Tyr161, compound 4 however, forms hydrogen bonds with Ser135, Asp129, Phe130 and Ile86 instead. The results from the present study suggests that malabaricones C (3) and E (4) could be employed as lead compounds for the development of new dengue antivirals from natural origin.

Natural DENV-2 NS2B/NS3 protease inhibitors from Myristica cinnamomea King

@#The NS2B/NS3 protease is crucial for the pathogenesis of the DENV. Therefore, the inhibition of this protease is considered to be the key strategy for the development of new antiviral drugs. In the present study, malabaricones C (3) and E (4), acylphenols from the fruits of Myristica cinnamomea King, have been respectively identified as moderate (27.33 ± 5.45 μM) and potent (7.55 ± 1.64 μM) DENV-2 NS2B/NS3 protease inhibitors, thus making this the first report on the DENV-2 NS2B/NS3 protease inhibitory activity of acylphenols. Based on the molecular docking studies, compounds 3 and 4 both have π-π interactions with Tyr161. While compound 3 has hydrogen bonding interactions with Gly151, Gly153 and Tyr161, compound 4 however, forms hydrogen bonds with Ser135, Asp129, Phe130 and Ile86 instead. The results from the present study suggests that malabaricones C (3) and E (4) could be employed as lead compounds for the development of new dengue antivirals from natural origin.

Dengue protease inhibition activity of selected Malaysian medicinal herbs.

Dengue fever is one of major health problem around the world including Malaysia. It is caused by the arthropode-borne flavivirus and transmitted by the bite of the Aedes aegypti or Aedes albopictus mosquito infected with one of the four dengue virus serotypes (DENV-1, DENV-2, DENV-3, or DENV-4). In this study, a screening exercise of various Malaysian medicinal plants showed that the extracts of Lawsonia inermis, Dryobalanops aromatica, Punica granatum, Zizyphus jujuba Lam. and Zingiber zerumbet exhibited potent inhibitory activity against NS2B-NS3 serine protease. The methanol extracts of Dryobalanops aromatica showed inhibition of 99.70 % at concentration of 200 µg/mL with IC50 value of 0.30 ± 0.16 µg/mL.

Dengue protease inhibition activity of selected Malaysian medicinal herbs

@#Dengue fever is one of major health problem around the world including Malaysia. It is caused by the arthropode-borne flavivirus and transmitted by the bite of the Aedes aegypti or Aedes albopictus mosquito infected with one of the four dengue virus serotypes (DENV-1, DENV-2, DENV-3, or DENV-4). In this study, a screening exercise of various Malaysian medicinal plants showed that the extracts of Lawsonia inermis, Dryobalanops aromatica, Punica granatum, Zizyphus jujuba Lam. and Zingiber zerumbet exhibited potent inhibitory activity against NS2B-NS3 serine protease. The methanol extracts of Dryobalanops aromatica showed inhibition of 99.70 % at concentration of 200 μg/mL with IC50 value of 0.30 ± 0.16 μg/mL.

In vitro antiplasmodial activity, macronutrients and trace metals in the medicinal plants: Phyllanthus spp. and Alpinia conchigera Griff.

An antiplasmodial screening of Phyllanthus debilis and Phyllanthus urinaria was carried out. The medicinal plants were extracted and evaluated for in vitro antiplasmodial activity against D10 (chloroquine-sensitive, CQS) and Gombak A (chloroquine-resistant, CQR) strains of Plasmodium falciparum. The methanolic crudes from the soxhlet extraction were active against both strains however, P. urinaria (IC50 8.9 µg/ml with CQR strain) exhibited better anti-malarial activity compared to P. debilis (IC50 12.2 µg/ml with CQR strain). Furthermore, the methanolic crude of P. urinaria obtained by the cold extraction has good anti-malarial activity towards CQS (IC50 4.1 µg/ml). The concentration of macronutrients (calcium and magnesium) and trace metals (copper, manganese, iron and zinc) from three Phyllanthus species i.e. P. debilis Klein ex Wild., Phyllanthus niruri L., P. urinaria L. and Alpinia conchigera Griff. were determined using microwave digestion method and analyzed by Flame Atomic Absorption Spectroscopy. Standard Reference Material 1547 (peach leaves) was used to validate the method throughout this study. The recovery values were in the range of 80% to 120% which were in very good agreement with the certified values. The three Phyllanthus species and leaves of A. conchigera showed the highest concentration of calcium compared to other metals and macronutrients studied. The significant presence of all the important macronutrients and trace metals which are essential for human health and well-being substantiate their use medicinally in traditional practices.

In vitro antiplasmodial activity, macronutrients and trace metals in the medicinal plants: Phyllanthus spp. and Alpinia conchigera Griff

An antiplasmodial screening of Phyllanthus debilis and Phyllanthus urinaria was carried out. The medicinal plants were extracted and evaluated for in vitro antiplasmodial activity against D10 (chloroquine-sensitive, CQS) and Gombak A (chloroquine-resistant, CQR) strains of Plasmodium falciparum. The methanolic crudes from the soxhlet extraction were active against both strains however, P. urinaria (IC50 8.9 μg/ml with CQR strain) exhibited better anti-malarial activity compared to P. debilis (IC50 12.2 μg/ml with CQR strain). Furthermore, the methanolic crude of P. urinaria obtained by the cold extraction has good anti-malarial activity towards CQS (IC50 4.1 μg/ml). The concentration of macronutrients (calcium and magnesium) and trace metals (copper, manganese, iron and zinc) from three Phyllanthus species i.e. P. debilis Klein ex Wild., Phyllanthus niruri L., P. urinaria L. and Alpinia conchigera Griff. were determined using microwave digestion method and analyzed by Flame Atomic Absorption Spectroscopy. Standard Reference Material 1547 (peach leaves) was used to validate the method throughout this study. The recovery values were in the range of 80% to 120% which were in very good agreement with the certified values. The three Phyllanthus species and leaves of A. conchigera showed the highest concentration of calcium compared to other metals and macronutrients studied. The significant presence of all the important macronutrients and trace metals which are essential for human health and wellbeing substantiate their use medicinally in traditional practices.

A new xanthone from Garcinia nitida.

A detailed chemical study on the stem bark of Garcinia nitida has led to the isolation of five xanthones. They are 1,6-dihydroxy-5-methoxy-6,6-dimethylpyrano[2',3':2,3]-xanthone (1), inophyllin B (2), osajaxanthone (3), 3-isomangostin (4) and rubraxanthone (5). The structures of these compounds were established using mainly 1-D and 2-D NMR spectroscopy ((1)H, (13)C, DEPT, COSY, HMBC and HMQC) while molecular masses were determined via MS techniques; 1 is a new compound.

Bioassay-guided isolation of a vasorelaxant active compound from Kaempferia galanga L.

Bioassay-guided fractionation was performed on a crude dichloromethane extract of Kaempferia galanga L. using chromatography techniques. Screening of the extract for biological activity started with the brine shrimp lethality bioassay, followed by the study of its antihypertensive activity on anaesthetized rats, which involved monitoring of the extract's effect on mean arterial blood pressure. The components of the fractions obtained from the separation procedures were analyzed using gas chromatography (GC). The yield of the CH(2)Cl(2) extract was 0.29% of the crude plant extract. Analysis of the data for brine shrimp lethality test using the Finney computer program showed that this extract exhibited potent bioactivity with an ED(50) value of 7.92+/-0.13 microgml(-1). Intravenous administration of the extract induced a dose-related reduction of basal mean arterial pressure (MAP) (130+/-5 mmHg) in the anaesthetized rat, with maximal effects seen after 5-10 min of injection. The gas chromatogram showed that the common compound in the active fractions obtained from the bioassay-guided fractionation of the CH(2)Cl(2) extract was ethyl cinnamate. This vasorelaxant active compound, ethyl cinnamate, was isolated as a colorless oil. Ethyl p-methoxycinnamic acid was also isolated as white needles but did not exhibit any relaxant effect on the precontracted thoracic rat aorta.

Sesquiterpenes and alkaloids from Scorodocarpus borneensis.

A new sesquiterpene, scodopin, and a mixture of three tryptamine-type alkaloids, scorodocarpines A-C, were isolated from the fruits of Scorodocarpus borneensis, together with a known hemisynthetic sesquiterpene, cadalene-beta-carboxylic acid, which was isolated from the bark. The structures of the new compounds were elucidated by interpretation of spectral data, especially tandem mass spectrometry for the alkaloid mixture.

Cytotoxic 3,4-secoapotirucallanes from Aaglaia argentea bark.

Nine 3,4-secoapotirucallanes, argentinic acids A-I, were isolated from the bark of Aglaia argentea and transformed to their methyl esters 1-9. The structures were determined by spectral and chemical means. Compounds 1-8 showed moderate cytotoxic activity against KB cells (IC50 1.0-3.5 microg/mL).

Argenteanones C-E and argenteanols B-E, cytotoxic cycloartanes from Aglaia argentea.

Seven new cycloartanes, argenteanones C-E (4-6) and argenteanols B-E (7-10), have been isolated from Aglaia argentea leaves. All of these compounds possess significant cytotoxic activity against KB cells (IC50 values between 3.7 and 6.2 micrograms/mL). Structure elucidation was performed by 2D NMR spectroscopy, aided by molecular modeling in the case of the side chain of compound 7.

Cytotoxic cycloartanes from Aglaia argentea.

Aglaia argentea leaves yielded three new cycloartanes: argenteanones A and B, and argenteanol. The first two possess cytotoxic activity against KB cells (IC50 7.5 micrograms ml-1 and 6.5 micrograms ml-1 respectively). Structural elucidation was done by two-dimensional NMR spectroscopy.

An antimitotic and cytotoxic chalcone from Fissistigma lanuginosum.

Bioassay-guided fractionation of an ethyl acetate extract of Fissistigma lanuginosum led to the isolation of the known chalcone pedicin [1], which inhibited tubulin assembly into microtubules (IC50 value of 300 microM). From the same EtOAc fraction, two new condensed chalcones, fissistin [2] and isofissistin [3], which showed cytotoxicity against KB cells, were also obtained, together with the inactive dihydropedicin [4] and 6,7-dimethoxy-5,8-dihydroxyflavone [5]. In addition, the aminoquinones 6, 8, and 9 were isolated from the alkaloid extract. These compounds were artifacts, prepared by treatment of 1, 4, and 2, respectively, with NH4OH. The structures of the new compounds were elucidated by spectral methods, especially 2D nmr.

A preliminary chemotaxonomic review of Kopsia (Apocynaceae).

The present paper is the result of a botanical and chemical study of the Indo-Pacific genus Kopsia (Plumerioideae-Rauvolfieae) Apocynaceae. Some of the species of this genus possess medicinal uses. A survey of the accepted taxa and their synonymy, based on the study of types, is presented. Studies on alkaloids provides chemotaxonomic information. Indeed, in some cases, chemical relationships occur between species belonging to the same botanical group.