Graph-based analysis of H-bond networks and unsupervised learning reveal conformational coupling in prion peptide segments.

In this study, we employed a comprehensive computational approach to investigate the physical chemistry of the water networks surrounding hydrated peptide segments, as derived from molecular dynamics simulations. Our analysis uncovers a complex interplay of direct and water-mediated hydrogen bonds that intricately weave through the peptides. We demonstrate that these hydrogen bond networks encode critical information about the peptides' conformational behavior, with the dimensionality of these networks showing sensitivity to the peptides' conformations. Additionally, we estimated the free-energy landscape of the peptides across various conformations, revealing that their structures are predominantly characterized by unfolded, partially folded, and folded configurations, resulting in broad and rugged free-energy surfaces due to the numerous degrees of freedom contributed by the surrounding solvent. Importantly, the structured nature of this free-energy landscape becomes obscured when conventional collective variables, such as the number of hydrogen bonds, are used. Our findings provide new insights into the molecular mechanisms that couple protein and solvent degrees of freedom, highlighting their significance in the functioning of biological systems.

Linear mixed model to identify the relationship between grain yield and other yield related traits and genotype selection for sorghum.

Sorghum is the most popular crop in arid and semi-arid areas, especially in Sub-Saharan African countries. Genotype effects, environmental and the interaction of genotype by environmental factors have an influence on phenotypic traits. The aim of the study is to identify the relationship between grain yield and other yield-related traits and select the genotypes which perform better in grain yield as well as to examine the association between the uncorrelated phenotypic traits and grain yield via mixed model. The data was generated using a lattice square design. Principal component analysis was used to generate uncorrelated variables for the mixed model. The study revealed that there was a difference in grain yield due to the treatment and there was a pairwise relationship among the phenotypic variables. 77.12% of the total variance of the original phenotypic variables was explained by the first three principal components and decided to use PCAs as input variables for the mixed model. All PCs had significant effects on grain yield as well as grain yield variability due to random effects associated with genotypes, genotype interaction by treatment, and replication within the treatment. The variability of grain yield due to genotype effect was explained about 45.73%, the variation of grain yield due to the interaction of genotype by the treatment was also explained about 39.06% and 1.55% of the variation of grain was explained by replication within treatment. The best performer genotypes recommended for mass production were G40 (Genotype 40), G186 (Genotype 186) and G196 (Genotype 196) without any constraint of environment. The genotypes recommended for mass production under irrigation conditions were G40 (Genotype 40), G62 (Genotype 62) and G192 (Genotype 192). G26 (Genotype 26), G55 (Genotype 55) and G49 (Genotype 49) were the genotypes recommended for mass production under stress conditions. Overall, the study recommends using a mixed model to fit the grain yield, and future work will focus on to evaluate the performance of genotypes under different environments and years of production.

High burden of ESBL and carbapenemase-producing gram-negative bacteria in bloodstream infection patients at a tertiary care hospital in Addis Ababa, Ethiopia.

BACKGROUND: Bloodstream infection due to beta-lactamase and carbapenemase-producing gram-negative bacteria poses a substantial challenge to the effectiveness of antimicrobial treatments. Therefore, this study aimed to investigate the magnitude of beta-lactamase, carbapenemase-producing gram-negative bacteria, and associated risk factors of bloodstream infections in patients at a tertiary care hospital, in Addis Ababa, Ethiopia. METHODS: An institutional-based cross-sectional study was conducted with convenience sampling techniques from September 2018 to March 2019. Blood cultures were analyzed from 1486 bloodstream infection suspected patients across all age groups. The blood sample was collected using two BacT/ALERT blood culture bottles for each patient. Gram stain, colony characteristics, and conventional biochemical tests were used to classify the gram-negative bacteria at the species level. Antimicrobial susceptibility testing was carried out to screen beta-lactam and carbapenem drug-resistant bacteria. The E-test was conducted for extended-spectrum-beta-lactamase and AmpC-beta-lactamase-producers. A modified and EDTA-modified carbapenem inactivation method was conducted for carbapenemase and metallo-beta-lactamases producers. Data collected using structured questionnaires and medical records were reviewed, encoded, and cleaned using EpiData V3.1. software. The cleaned data were exported and analyzed using SPSS version 24 software. Descriptive statistics and multivariate logistic registration models were used to describe and assess factors associated with acquiring drug-resistant bacteria infection. A p-value <0.05 was considered statistically significant. RESULT: Among 1486 samples, 231 gram-negative bacteria were identified; of these, 195(84.4%) produce drug-hydrolyzing enzymes, and 31(13.4%) produce more than one drug-hydrolyzing enzyme. We found 54.0% and 25.7% of the gram-negative bacteria to be extended-spectrum-beta-lactamase and carbapenemase-producing, respectively. The extended-spectrum-beta-lactamase plus AmpC-beta-lactamase-producing bacteria account for 6.9%. Among the different isolates Klebsiella pneumonia 83(36.7%) was the highest drug-hydrolyzing enzyme-producing bacteria. Acinetobacter spp 25(53.2%) was the most carbapenemase producer. Extended-spectrum-beta-lactamase and carbapenemase-producing bacteria were high in this study. A significant association between age groups and extended-spectrum-beta-lactamase producer bacterial infection was seen, with a high prevalence in neonates (p = <0.001). Carbapenemase showed a significant association with patients admitted to the intensive care unit (p = 0.008), general surgery (p = 0.001), and surgical intensive care unit (p = 0.007) departments. Delivery of neonates by caesarean section, and insertion of medical instruments into the body were exposing factors for carbapenem-resistant bacterial infection. Chronic illnesses were associated with an extended-spectrum-beta-lactamase-producing bacterial infection. Klebsiella pneumonia and Acinetobacter species showed the greatest rates of extensively drug-resistant (37.3%) and pan-drug-resistance (76.5%), respectively. According to the results of this study, the pan-drug-resistance prevalence was found to be alarming. CONCLUSION: Gram-negative bacteria were the main pathogens responsible for drug-resistant bloodstream infections. A high percentage of extended-spectrum-beta-lactamase and carbapenemase-producer bacteria were found in this study. Neonates were more susceptible to extended-spectrum-beta-lactamase and AmpC-beta-lactamase-producer bacteria. Patients in general surgery, caesarean section delivery, and intensive care unit were more susceptible to carbapenemase-producer bacteria. The suction machines, intravenous lines, and drainage tubes play an important role in the transmission of carbapenemase and metallo-beta-lactamase-producing bacteria. The hospital management and other stakeholders should work on infection prevention protocol implementation. Moreover, special attention should be given to all types of Klebsiella pneumoniae and pan-drug resistance Acinetobacter spp transmission dynamics, drug resistance genes, and virulence factors.

Benzo[b]naphtho[2,1-d]furans and 2-Phenylnaphthalenes from Streblus usambarensis.

Three new benzo[b]naphtho[2,1-d]furans, usambarins A-C (1-3), five new 2-phenylnaphthalenes, usambarins D-H (4-8), a new flavan (9), and a new phenyl-1-benzoxepin (10) as well as two known compounds (11 and 12) were isolated from the extract of the stem and roots of Streblus usambarensis (Moraceae). The structures were deduced using NMR spectroscopic and mass spectrometric analyses, and those of compounds 1 and 4 were confirmed by X-ray crystallography. Usambarin D (4) demonstrated moderate antibacterial activity (MIC 9.0 µM) against Bacillus subtilis, while none of the tested compounds were effective against Escherichia coli.

A new C-C linked benzophenathridine-2-quinoline dimer, and the antiplasmodial activity of alkaloids from Zanthoxylum holstzianum.

The CH2Cl2/MeOH (1:1) extract of Zanthoxylum holstzianum stem bark showed good antiplasmodial activity (IC50 2.5 ± 0.3 and 2.6 ± 0.3 µg/mL against the W2 and D6 strains of Plasmodium falciparum, respectively). From the extract five benzophenanthridine alkaloids [8-acetonyldihydrochelerythrine (1), nitidine (2), dihydrochelerythine (3), norchelerythrine (5), arnottianamide (8)]; a 2-quinolone alkaloid [N-methylflindersine (4)]; a lignan [4,4'-dihydroxy-3,3'-dimethoxylignan-9,9'-diyl diacetate (7)] and a dimer of a benzophenanthridine and 2-quinoline [holstzianoquinoline (6)] were isolated. The CH2Cl2/MeOH (1:1) extract of the root bark afforded 1, 3-6, 8, chelerythridimerine (9) and 9-demethyloxychelerythrine (10). Holstzianoquinoline (6) is new, and is the second dimer linked by a C-C bond of a benzophenanthridine and a 2-quinoline reported thus far. The compounds were identified based on spectroscopic evidence. Amongst five compounds (1-5) tested against two strains of P. falciparum, nitidine (IC50 0.11 ± 0.01 µg/mL against W2 and D6 strains) and norchelerythrine (IC50 value of 0.15 ± 0.01 µg/mL against D6 strain) were the most active.

Anti-HIV crotocascarin ω from Kenyan Croton dichogamus.

An anti-HIV methanol-soluble fraction of a 1:1 CH2Cl2:CH3OH extract of twigs of a Kenyan Croton dichogamus yielded seven compounds, the new crotocascarin ω (1), the known ß-oplopanone (2), dihydroconiferyl acetate (3), 3'(4''-hydroxyphenyl)-propyl benzoate (4), lupeol, sitosterol and stigmasterol. Crotocascarin ω (90%) inhibited HIV-1 replication with an IC50 value of 5.3 nM, and the compound was cytotoxic towards MT-4 cells presenting an IC50 value of 84 µM. In silico modelling showed that the anti-HIV activity for compound 1 could be through the HIV-1 protease inhibition.

Anti-HIV Ermiasolides from Croton megalocarpus.

In recent years, elucidation of novel anti-HIV bioactive compounds from natural products is gaining importance rapidly, not only from the research and publications, but also from controlled clinical studies. Here we report three new anti-HIV eudesmane-type sesquiterpenes, 5ß-Hydroxy-8α-methoxy eudesm-7(11)-en-12,8-olide (1), 5ß,8α-Dihydroxy eudesm-7(11)-en-12,8-olide (2) and 5ß-Hydroxy-8H-ß-eudesm-7(11)-en-12,8-olide (3). These are trivially named ermiasolide A-C and were isolated from the bark of Croton megalocarpus. 5ß-Hydroxy-8α-methoxy eudesm-7(11)-en-12,8-olide (1), showed the highest anti-HIV activity by inhibiting 93% of the viral replication with an IC50 = 0.002 µg/mL. On the other hand, 5ß-Hydroxy-8H-ß-eudesm-7(11)-en-12,8-olide (3) and 5ß,8α-dihydroxy eudesm-7(11)-en-12,8-olide (2), inhibited viral replication by 77.5% at IC50 = 0.04 µg/mL and 69.5% at IC50 = 0.002 µg/mL, respectively. Molecular docking studies showed that the proposed mechanism of action leading to these results is through the inhibition of HIV-protease.

In vitro anti-HIV and cytotoxic effects of pure compounds isolated from Croton macrostachyus Hochst. Ex Delile.

Croton macrostachyus is an important plant in traditional African medicine, widely utilized to treat a variety of diseases. In Kenya, HIV-infected patients use leaf and root decoctions of the plant as a cure for cough, back pain, bleeding, skin diseases, warts, pneumonia, and wounds. This study aimed to evaluate the anti-HIV activities and cytotoxic effects of extracts and chemical constituents isolated from C. macrostachyus. In our previous study we demonstrated that the hexane, CH2Cl2, ethyl acetate and methanol soluble fractions of a 1:1 v/v/ CH2Cl2/MeOH crude extracts of the leaves and stem bark of C. macrostachyus exhibited potent anti-HIV activities against HIV-1 with IC50 values ranging from 0.02-8.1 µg/mL and cytotoxicity effects against MT-4 cells ranging from IC50 = 0.58-174 µg/mL. Hence, hexane soluble extract of 1:1 v/v/ CH2Cl2/MeOH crude extract of the leaves of C. macrostachyus, that was more potent against HIV-1 at IC50 = 0.02 µg/mL was subjected to column chromatography leading to the isolation of 2-methoxy benzyl benzoate (1), lupenone (2), lupeol acetate (3), betulin (4), lupeol (5), sitosterol (6) and stigmasterol (7). Lupenone (2), lupeol acetate (3) and betulin (4) exhibited anti-HIV-1 inhibition at IC50 = 4.7 nM, 4.3 and 4.5 µg/mL respectively. The results obtained from this study support the potential of C. macrostachyus, as a source of anti-HIV constituents.

Constituents of Croton megalocarpus with Potential Anti-HIV Activity.

Reported herein is an anti-HIV monochlorinated compound, 1ß-acetoxy-3ß-chloro-5α,6α-dihydroxycrotocascarin L (1), of the rare crotofolane diterpenoid class. Compound 1, a suspected artifact of extraction, along with the previously undescribed 11ß-acetoxycrotocascarin L (2) and a known compound, crotocascarin K (3), were isolated from the bark of Croton megalocarpus, a Kenyan oil-producing seed crop. Compounds 1 and 3 inhibited HIV-1 replication with IC50 values of 28 and 5.5 nM, respectively. Furthermore, both compounds lacked cytotoxicity toward MT-4 cells and FM-55-M1 cells at concentrations of up to 50 µM. Compounds 1 and 3 were both found to inhibit HIV-1 protease.

A new ß-hydroxydihydrochalcone from Tephrosia uniflora, and the revision of three ß-hydroxydihydrochalcones to flavanones.

The CH2Cl2/MeOH (1:1) extract of the stems of Tephrosia uniflora yielded the new ß-hydroxydihydrochalcone (S)-elatadihydrochalcone-2'-methyl ether (1) along with the three known compounds elongatin (2), (S)-elatadihydrochalcone (3), and tephrosin (4). The structures were elucidated by NMR spectroscopic and mass spectrometric data analyses. Elongatin (2) showed moderate antibacterial activity (EC50 of 25.3 µM and EC90 of 32.8 µM) against the Gram-positive bacterium Bacilus subtilis, and comparable toxicity against the MCF-7 human breast cancer cell line (EC50 of 41.3 µM). Based on the comparison of literature and predicted NMR data with that obtained experimentally, we propose the revision of the structures of three ß-hydroxydihydrochalcones to flavanones.

Cytotoxicity and anti-HIV activities of extracts of the twigs of Croton dichogamus Pax.

BACKGROUND: Acquired immunodeficiency syndrome (AIDS) is a clinical syndrome resulting from infection with human immunodeficiency virus (HIV), which causes profound immunosuppression. Anti-HIV drugs that are currently available are chemically synthesized and are frequently limited by side effects, the emergence of drug resistance, affordability, and availability, with over 5 million people in the world lacking access to treatment. As a result, to discover new anti-HIV agents, we investigated the effects of Kenyan C. dichogamus extracts on the laboratory-adapted strain HIV-1IIIB in human T-lymphocytic MT-4 cells. METHODS: Four soluble fractions of 1:1 v/v CH2Cl2:MeOH extract of the twigs of C. dichogamus Pax were tested for their replication inhibition activity against the laboratory-adapted strain HIV-1IIIB in the human T-lymphocytic MT-4 cell line. The plant extracts were further evaluated for their cytotoxicity in MT-4 cells using the MTT assay. RESULTS: The cytotoxicity CC50 values of the methanol and methylene chloride soluble fractions of C. dichogamus were found to be between 19.58 ± 0.79 and 167 ± 0.8 µg/ml, respectively. The hexane, methylene chloride, and methanol soluble fractions of the 1:1 v/v CH2Cl2:MeOH extract of the twigs of C. dichogamus showed inhibition of the HIV-1IIIB laboratory-adapted strain in a virus-infected cell culture antiviral assay. The methanol soluble fraction of the 1:1 v/v CH2Cl2:MeOH extract of the twigs of C. dichogamus showed significant anti-HIV activity by inhibiting more than 90% of viral-induced cytopathic effects with an IC50 value of 0.06 ± 0.01 µg/ml, giving an SI of 318.5. CONCLUSION: Based on our findings, the methanol soluble fraction of the 1:1 v/v CH2Cl2:MeOH extract of the twigs of C. dichogamus has shown potential efficacy in inhibiting viral replication and could be considered a promising candidate for further studies.

Antileishmanial and cytotoxic activity of secondary metabolites from Taberneamontana ventricosa and two aloe species.

In this study, the antileishmanial and cytotoxic activities of secondary metabolites isolated from Tabernaemontana ventricosa Hochst. ex A. DC., Aloe tororoana Reynolds, and Aloe schweinfurthii var. labworana Reynolds were investigated. Overall, nineteen known compounds were isolated from the three plant species. The compounds were characterized based on their spectroscopic data. Voacristine and aloenin were the most active compounds against promastigotes of antimony-sensitive Leishmania donovani (IC50 11 ± 5.2 µM and 26 ± 6.5 µM, respectively) with low toxicity against RAW264.7, murine monocyte/macrophage-like cells. The in silico docking evaluation and in vitro NO generation assay also substantially support the antileishmanial effects of these compounds. In a cytotoxicity assay against cancer and normal cell lines, ursolic acid highly inhibited proliferation of lung cancer cells, A549 (IC50 6.61 ± 0.7 µM) while voacristine was moderately active against human liver cancer cells, HepG2 (IC50 23.0 ± 0.0 µM). All other compounds were inactive against the test parasites and cell lines. [Formula: see text].

Cytotoxicity of isoflavones from Millettia dura.

The first phytochemical investigation of the flowers of Millettia dura resulted in the isolation of seven isoflavones, a flavonol and a chalcone. Eleven isoflavones and a flavonol isolated from various plant parts from this plant were tested for cytotoxicity against a panel of cell lines, and six of these showed good activity with IC50 values of 6-14 µM. Durmillone was the most active with IC50 values of 6.6 µM against A549 adenocarcinomic human alveolar basal epithelial cancer cell line with low cytotoxicity against the non-cancerous cell lines BEAS-2B (IC50 = 58.4 µM), LO2 hepatocytes (IC50 78.7 µM) and CCD19Lu fibroblasts (IC50 >100 µM).

Solar Driven Photocatalytic Activity of Porphyrin Sensitized TiO2: Experimental and Computational Studies.

The absence of a secure long-term sustainable energy supply is recognized as a major worldwide technological challenge. The generation of H2 through photocatalysis is an environmentally friendly alternative that can help solve the energy problem. Thus, the development of semiconductor materials that can absorb solar light is an attractive approach. TiO2 has a wide bandgap that suffers from no activity in the visible spectrum, limiting its use of solar radiation. In this research, the semiconductor absorption profile was extended into the visible region of the solar spectrum by preparing porphyrin-TiO2 (P-TiO2) composites of meso-tetra(4-bromophenyl)porphyrin (PP1) and meso-tetra(5-bromo-2-thienyl)porphyrin (PP2) and their In(III), Zn(II) and Ga(III) metal complexes. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations were performed on the porphyrins to gain insight into their electron injection capability. The results demonstrate that P-TiO2 systems merit further in-depth study for applications that require efficient photocatalytic H2 generation.

In Vitro Cytotoxicity and Anti-HIV Activity of Crude Extracts of Croton macrostachyus, Croton megalocarpus and Croton dichogamus.

INTRODUCTION: Human immunodeficiency virus (HIV) affects the body's defense mechanisms and leads to a number of opportunistic infections which later cause fatality as a result of an acquired immunodeficiency syndrome (AIDS). More than half a million individuals have lost their life in 2020 due to this disease. Antiretroviral drugs have played a great role in improving the quality of life of HIV infected individuals. The side effects of these drugs coupled with resistance of the virus to the various regimens, necessitates the search for potentially new and effective antiretroviral medication. The objective of this study is to evaluate anti-HIV activity of crude extracts of three Croton plants. METHODS: As part of our effort in screening anti-HIV medications, we evaluated the cytotoxicity and anti-HIV activity of three Croton species used as herbal medicine in Africa. Crude extracts of Croton macrostachyus, Croton megalocarpus and Croton dichogamus were tested for their replication inhibition activity against laboratory adapted strains HIV-1IIIB in Human T-lymphocytic MT-4 cell line. RESULTS: Based on our findings, the crude aerial part extract of C. dichogamus displayed the highest anti-HIV activity by inhibiting 73.74% of viral induced cytopathic effect (CPE) at IC50 value of 0.001 + 0.00 µg/mL giving a selectivity index (SI) of 3116.0. In addition, the crude leaf extract of C. megalocarpus showed higher anti-HIV activity by inhibiting 74.65% of CPE at IC50 value of 0.05 + 0.03 µg/mL giving an SI of 571.3. CONCLUSION: Out of five extracts from three Croton species screened for anti-HIV activity using human T-lymphocytic MT-4 cells, the leaf extract of Croton megalocarpus and aerial part extract of Croton dichogamus could be considered as promising extracts as they display high antiviral activity with low toxicity and high selectivity index values. To investigate the active constituents responsible for the anti-HIV activity, chemical identification of the active constituents is now in progress in our laboratory. Since there is no previously reported anti-HIV activity for these plants, there is a great need to isolate the compounds responsible for the noted activity.

Synergistic anti-inflammatory activities of a new flavone and other flavonoids from Tephrosia hildebrandtii vatke.

A new flavone, named hildeflavone (1) along with 7 other known flavonoids were isolated from the aerial parts of Tephrosia hildebrandtii Vatke. Their characterisation was based on NMR and MS data analysis. The anti-inflammatory properties of the crude extract, isolated compounds and combination of the compounds were investigated in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs). Treatment of the LPS-stimulated PBMCs with the isolated flavonoids at a concentration of 100 µM significantly reduced the production of interleukins (IL-1ß, IL-2 and IL-6), interferon-gamma (IFN-γ), granulocyte macrophage-colony stimulating factor (GM-CSF) and tumour necrosis factor-alpha (TNF-α). It was also found that the combination of a flavone and flavanones exhibited remarkable synergistic anti-inflammatory effects on the production of the cytokines.[Figure: see text].

Antiplasmodial and antileishmanial flavonoids from Mundulea sericea.

Five known compounds (1-5) were isolated from the extract of Mundulea sericea leaves. Similar investigation of the roots of this plant afforded an additional three known compounds (6-8). The structures were elucidated using NMR spectroscopic and mass spectrometric analyses. The absolute configuration of 1 was established using ECD spectroscopy. In an antiplasmodial activity assay, compound 1 showed good activity with an IC50 of 2.0 µM against chloroquine-resistant W2, and 6.6 µM against the chloroquine-sensitive 3D7 strains of Plasmodium falciparum. Some of the compounds were also tested for antileishmanial activity. Dehydrolupinifolinol (2) and sericetin (5) were active against drug-sensitive Leishmania donovani (MHOM/IN/83/AG83) with IC50 values of 9.0 and 5.0 µM, respectively. In a cytotoxicity assay, lupinifolin (3) showed significant activity on BEAS-2B (IC50 4.9 µM) and HePG2 (IC50 10.8 µM) human cell lines. All the other compounds showed low cytotoxicity (IC50 > 30 µM) against human lung adenocarcinoma cells (A549), human liver cancer cells (HepG2), lung/bronchus cells (epithelial virus transformed) (BEAS-2B) and immortal human hepatocytes (LO2).

Inhibition of Proinflammatory Cytokine Release by Flavones and Flavanones from the Leaves of Dracaena steudneri Engl.

The leaves of Dracaena steudneri yielded 6 new flavonoids-3,5,7-trihydroxy-6-methyl-3',4'-methylenedioxyflavone (1: ), 5,7-dihydroxy-3-methoxy-6-methyl-3',4'-methylenedioxyflavone (2: ), 3,5,7-trihydroxy-6-methoxy-3',4'-methylenedioxyflavone (3: ), (2S,3S)-3,7-dihydroxy-6-methoxy-3',4'-methylenedioxyflavanone (4: ), 4',5,7-trihydroxy-3,3',8-trimethoxy-6-methylflavone (5: ), (2R) 7-hydroxy-2',8-dimethoxyflavanone (6: )-together with 13 known congeners. Their structures were established using spectroscopic and spectrometric methods including NMR, CD, and HRMSn measurements. The compounds were evaluated for their anti-inflammatory potential through measurement of the levels of cytokines IL-1ß, IL-2, GM-CSF, and TNF-α in the supernatant of human peripheral blood mononuclear cells stimulated by lipopolysaccharide. Flavones derivatives 1: -4: with a C-3'/4' methylenedioxy substituent led to a substantial increase in the production of IL-1ß and GM-CSF out of 4 pro-inflammatory cytokines relative to LPS control. Quercetin derivatives 5, 11,: and 13: with a hydroxyl group at C-4' inhibited the production of IL-2, GM-CSF, and TNF-α. The presence of a C-2/C-3 double bond in 14: was pivotal to the significantly stronger (0.4 to 27.5% of LPS control) inhibitory effect compared to its dihydro derivative 8: (36.2 to 262.7% of LPS control) against all tested cytokines. It is important to note that the inhibitory activity of 14: was substantially higher than that of the standard drug used, ibuprofen.

Anti-inflammatory steroidal sapogenins and a conjugated chalcone-stilbene from Dracaena usambarensis Engl.

Four new steroidal sapogenins, dracaenogenins CF (1-4), a new conjugated chalcone-stilbene, 3''-methoxycochinchinenene H (5) together with eight known compounds namely, (25S)-spirosta-1,4-dien-3-one (6), trans-resveratrol (7), 4,4'-dihydroxy-3'-methoxychalcone (8), N-trans-coumaroyltyramine (9), N-trans-p-coumaroyloctopamine (10), N-trans-feruloyloctopamine (11), 7-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-N2,N3-bis(4-hydroxyphenethyl)-6-methoxy-1,2-dihydronaphthalene-2,3-dicarboxamide (12) and grossamide (13) were isolated from the stems of Dracaena usambarensis Engl. from Kenya. It is important to note that compounds 12 and 13 are being reported from this genus for the first time. Structural elucidation of the isolated compounds was done using spectroscopic (NMR, UV, IR, optical rotation) and spectrometric (HRESIMS) techniques. The absolute and relative configurations of the isolated compounds were determined by employing single crystal X-ray crystallography analysis, NOESY correlations and coupling constants. The anti-inflammatory potencies of the isolated compounds were evaluated by measuring the levels of four cytokines (IL-1ß, IL-2, GM-CSF and TNF-α) in the supernatant media of human peripheral blood mononuclear cells (PBMCs) stimulated by lipopolysaccharide (LPS). At the tested concentration of 100 µM, the new conjugated chalcone-stilbene 5, the dihydrochalcone, 8 and the lignanamide, 13 were substantially more potent than the standard drug, ibuprofen, inhibiting the release of all the cytokines, IL-1ß, IL-2, GM-CSF and TNF-α from 0.06-58.04% compared to LPS control. These compounds should therefore be considered for development into anti-inflammatory drug candidates. Compound 7 significantly decreased the release of GM-CSF (6.11% of LPS control) and TNF-α (18.35% of LPS control). The cytokine TNF-α was sensitive to all the tested compounds 1-13.

Isoflavones from the seedpods of Tephrosia vogelii and pyrazoisopongaflavone with anti-inflammatory effects.

Phytochemical investigation of Tephrosia vogelii seedpods led to the isolation of twelve compounds: vogelisoflavone A (1), vogelisoflavone B (2), isopongaflavone (3), onogenin, luteolin, 4',7-dihydroxy-3'-methoxyflavanone, trans-p-hydroxycinnamic acid, tephrosin, 2-methoxygliricidol, dehydrorotenone, 6a,12a-dehydro-α-toxicarol and pinoresinol. Compounds 1 and 2 are reported as new natural products. Isopongaflavone (3) was structurally modified using hydrazine to pyrazoisopongaflavone (4). These compounds were characterized based on their NMR and HRESIMS data. Further, four compounds (1-4) were evaluated for their anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs). Treatment of the LPS-stimulated PBMCs with the compounds at a concentration of 100 µM suppressed the secretion of interleukin IL-1ß interferon-gamma (IFN-γ), granulocyte macrophage-colony stimulating factor (GM-CSF) and tumour necrosis factor-alpha (TNF-α).