Phytochemicals from Pterocarpus angolensis DC and Their Cytotoxic Activities against Breast Cancer Cells.

Pterocarpus anglonesis DC is an indigenous medicinal plant belonging to the Pterocarpus genus of the Fabaceae family. It is used to treat stomach problems, headaches, mouth ulcers, malaria, blackwater fever, gonorrhea, ringworm, diarrhea, heavy menstruation, and breast milk stimulation. Column chromatography of the stem bark extracts resulted in the isolation of eight compounds, which included friedelan-3-one (1), 3α-hydroxyfriedel-2-one (2), 3-hydroxyfriedel-3-en-2-one (3), lup-20(29)-en-3-ol (4), Stigmasta-5-22-dien-3-ol (5), 4-O-methylangolensis (6), (3ß)-3-acetoxyolean-12-en-28-oic acid (7), and tetradecyl (E)-ferulate (8). The structures were established based on NMR, IR, and MS spectroscopic analyses. Triple-negative breast cancer (HCC70), hormone receptor-positive breast cancer (MCF-7), and non-cancerous mammary epithelial cell lines (MCF-12A) were used to test the compounds' cytotoxicity. Overall, the compounds showed either no toxicity or very low toxicity to all three cell lines tested, except for the moderate toxicity displayed by lupeol (4) towards the non-cancerous MCF-12A cells, with an IC50 value of 36.60 µM. Compound (3ß)-3-acetoxyolean-12-en-28-oic acid (7) was more toxic towards hormone-responsive (MCF-7) breast cancer cells than either triple-negative breast cancer (HCC70) or non-cancerous breast epithelial (MCF-12A) cells (IC50 values of 83.06 vs. 146.80 and 143.00 µM, respectively).

Inhibitory effects of selected cannabinoids against dipeptidyl peptidase IV, an enzyme linked to type 2 diabetes.

Ethnopharmacological relevance: In recent times the decriminalisation of cannabis globally has increased its use as an alternative medication. Where it has been used in modern medicinal practises since the 1800s, there is limited scientific investigation to understand the biological activities of this plant. Aim of the study: Dipeptidyl peptidase IV (DPP-IV) plays a key role in regulating glucose homeostasis, and inhibition of this enzyme has been used as a therapeutic approach to treat type 2 diabetes. However, some of the synthetic inhibitors for this enzyme available on the market may cause undesirable side effects. Therefore, it is important to identify new inhibitors of DPP-IV and to understand their interaction with this enzyme. Methods: In this study, four cannabinoids (cannabidiol, cannabigerol, cannabinol and Δ9-tetrahydrocannabinol) were evaluated for their inhibitory effects against recombinant human DPP-IV and their potential inhibition mechanism was explored using both in vitro and in silico approaches. Results: All four cannabinoids resulted in a dose-dependent response with IC50 values of between 4.0 and 6.9 µg/mL. Kinetic analysis revealed a mixed mode of inhibition. CD spectra indicated that binding of cannabinoids results in structural and conformational changes in the secondary structure of the enzyme. These findings were supported by molecular docking studies which revealed best docking scores at both active and allosteric sites for all tested inhibitors. Furthermore, molecular dynamics simulations showed that cannabinoids formed a stable complex with DPP-IV protein via hydrogen bonds at an allosteric site, suggesting that cannabinoids act by either inducing conformational changes or blocking the active site of the enzyme. Conclusion: These results demonstrated that cannabinoids may modulate DPP-IV activity and thereby potentially assist in improving glycaemic regulation in type 2 diabetes.

Mechanochemically-Assisted Passerini Reactions: A Practical and Convenient Method for the Synthesis of Novel α-Acyloxycarboxamide Derivatives.

A carboxylic acid, an aldehyde, and an isonitrile were combined in a single step (Passerini reaction) under mechanochemical activation to produce several α-acyloxycarboxamide derivatives in high to excellent yields within 15 min of milling. Mechanochemistry, when combined with the diversity provided by multicomponent reactions, enables the efficient synthesis of the target compounds, with great atom economy, shorter reaction times, and experimental simplicity. The method allows for the rapid production of a vast library of complex compounds from a limited number of substrates.

N-Formamide as a carbonyl precursor in the catalytic synthesis of Passerini adducts under aqua and mechanochemical conditions.

A new simple, efficient, and environmentally friendly protocol is presented for the catalytic synthesis of α-acyloxycarboxamides using N-formamides as a carbonyl precursor under aqua and mechanochemical conditions. Immobilized sulfuric acid on silica gel was employed for the synthesis of desired products, via the reaction of benzoic acid, 1-napthylisocyanide and various heterocyclic N-formamides. After a careful optimization of the reaction conditions, the desired Passerini products were obtained in high to excellent yields in short reaction times (10-30 min) at room temperature. The highly efficient and environmentally friendly method provides a facile access to a library of α-acyloxycarboxamides derivatives for future research on bioactivity screening.

Cytotoxicity and antimicrobial activity of isolated compounds from Monsonia angustifolia and Dodonaea angustifolia.

ETHNOPHARMACOLOGICAL RELEVANCE: Monsonia angustifolia is traditionally used to treat anthrax, heartburn, diarrhea, eye infections and hemorrhoids. Dodonaea angustifolia is frequently used as a treatment for dental pain, microbial infections and jungle fever. The two plant species were selected due to the presence of secondary metabolites such as coumarins, flavonoids, terpenoids, saponins and polyphenolics from the crude extracts, which exhibit pharmacological significance. The pure isolated compounds from the crude extracts are known for their diverse structures and interesting pharmacophores. AIM: To isolate and identify antibacterial and antifungal chemical constituents from Monsonia angustifolia and Dodonaea angustifolia plant extracts and evaluate the cytotoxicity of pure compounds from the crude extracts. MATERIALS AND METHODS: Extractives from M. angustifolia and D. angustifolia plants were isolated using chromatographic techniques and structures were elucidated based on NMR, IR and MS spectroscopic techniques. A microplate serial dilution method was used to evaluate the antibacterial activity of extracts and pure compounds against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and antifungal activity against Candida albicans and Cryptococcus neoformans. The cytotoxicity was determined using the 3-(4, 5-dimethylthiazol)-2, 5-diphenyl tetrazolium bromide (MTT) assay. RESULTS: The dichloromethane, ethyl acetate and methanol crude extracts from the plants exhibited significant inhibition of microbial growth. The phytochemical investigation of these active crude extracts led to the isolation of five pure active compounds, 5-methoxyjusticidin A (1), cis-phytyl diterpenoidal fatty acid ester (2), stigmasterol (3), ß-sitosterol (4) and 5-hydroxy-7,4'-dimethoxyflavone (5). Stigmasterol (3) showed good antifungal activity against Cryptococcus neoformans with a minimum inhibition concentration (MIC) of 25 µg/mL and Candida albicans (MIC = 50 µg/mL). CONCLUSION: Compounds (1-5) isolated from Monsonia angustifolia and Dodonaea angustifolia showed antibacterial and antifungal activities and were non-toxic against Madin-Darby canine kidney (MDCK) cells and VERO monkey kidney (VERO) cells.

In Vitro and In Silico Potential Inhibitory Effects of New Biflavonoids from Ochna rhizomatosa on HIV-1 Integrase and Plasmodium falciparum.

The aim of this study was to identify bioactive secondary metabolites from Ochna rhizomatosa with potential inhibitory effects against HIV and Plasmodium falciparum. A phytochemical study of O. rhizomatosa root barks resulted in the identification of three new biflavonoids (1-3), along with four known ones (4-7). Compound 7 (Gerontoisoflavone A) was a single flavonoid present in the rootbark of the plant and was used as a reference. Compound 1 (IC50 = 0.047 µM) was the only one with a noteworthy inhibitory effect against HIV-1 integrase in vitro. Chicoric acid (IC50 = 0.006 µM), a pure competitive inhibitor of HIV-1 integrase, was used as control. Compound 2 exhibited the highest antiplasmodial activity (IC50 = 4.60 µM) against the chloroquine-sensitive strain of Plasmodium falciparum NF54. Computational molecular docking revealed that compounds 1 and 2 had the highest binding score (-121.8 and -131.88 Kcal/mol, respectively) in comparison to chicoric acid and Dolutegravir (-116 and -100 Kcal/mol, respectively), towards integrase receptor (PDB:3LPT). As far as Plasmodium-6 cysteine s48/45 domain inhibition is concerned, compounds 1 and 2 showed the highest binding scores in comparison to chloroquine, urging the analysis of these compounds in vivo for disease treatment. These results confirm the potential inhibitory effect of compounds 1 and 2 for HIV and malaria treatment. Therefore, our future investigation to find inhibitors of these receptors in vivo could be an effective strategy for developing new drugs.

Effects of Tartrazine on Some Sexual Maturation Parameters in Immature Female Wistar Rats.

Over the past century, the average age for onset of puberty has declined. Several additives present in our food are thought to contribute significantly to this early puberty which is recognized to also affect people's health in later life. On this basis, the impact of 40-days unique oral administration of the food dye tartrazine (7.5, 27, and 47 mg/kg BW doses) was evaluated on some sexual maturation parameters on immature female Wistar rats. Vaginal opening was evaluated during the treatment period. At the end of the treatments, animals were sacrificed (estrus phase) and the relative weight of reproductive organs, pituitary gonadotrophin and sexual steroids level, cholesterol level in ovaries and folliculogenesis were evaluated. Compared to the control group, animals receiving tartrazine (47 mg/kg BW) showed significantly high percentage of early vaginal opening from day 45 of age, and an increase in the number of totals, primaries, secondaries, and antral follicles; a significant increase in serum estrogen, LH and in uterine epithelial thickness. Our findings suggest that tartrazine considerably disturbs the normal courses of puberty. These results could validate at least in part the global observations on increasingly precocious puberty in girls feeding increasingly with industrially processed foods.

13-amino derivatives of dehydrocostus lactone display greatly enhanced selective toxicity against breast cancer cells and improved binding energies to protein kinases in silico.

The biological activities of dehydrocostus lactone and its analogues are suggested to be mediated by the lactone ring and α,ß-methylene-γ-lactone. However, few studies exist on the structure-activity relationship of 13-amino derivatives of dehydrocostus latone. In this study new 13-amino derivatives of dehydrocostus lactone DHLC (1-4) were synthesized through Michael addition reactions, and were screened against three different breast cancer cell lines, namely hormone receptor positive breast cancer (MCF-7), triple-negative breast cancer (HCC70), and non-tumorigenic mammary epithelial (MCF-12A) cell lines. Dehydrocostus lactone (DHLC) exhibited IC50 values of 1.11 (selectivity index (SI) = 0.06), 24.70 (SI = 0.01) and 0.07 µM against HCC70, MCF-7 and MCF-12A cells, respectively. All the amino derivatives, except DHLC-3 displayed low micromolar IC50 values (ranging from 0.07-4.24 µM) against both breast cancer cell lines, with reduced toxicity towards MCF-12A non-tumorigenic mammary epithelial cells (SI values ranging from 6.00-126.86). DHLC-1 and DHLC-2 demonstrated the greatest selectivity for the MCF-7 cells (with SI of 121 and 126.86 respectively) over the MCF-12A cells. This reveals that, overall, the derivatives display greatly improved selectivity for breast cancer over non-tumorigenic mammary epithelial cells, with between 100-fold and 12 000-fold higher SI values. The improved docking scores were recorded for all the 13-amino dehydrocostus lactone derivatives for the enzymes analyzed. Compounds DHLC-4, and DHLC-3 recorded higher docking scores of -7.33 and -5.97 Kca/mol respectively, compared to the parent structure, dehydrocostus lactone (-5.34 Kca/mol) for protein kinase (PKC) theta (1XJD) and -6.22 and -5.88 Kca/mol, respectively for protein kinase iota (1RZR). The compounds further showed promising predicted adsorption, distribution, metabolisms and excretion (ADME) properties. Predicting the ADME properties of these derivatives is of importance in evaluating their drug-likeness, which could in turn be developed into potential drug candidates.

Catalytic Performance of Immobilized Sulfuric Acid on Silica Gel for N-Formylation of Amines with Triethyl Orthoformate.

In the search for convenient, green, and practical catalytic methods for the current interest in organic synthesis, a simple, green, and highly efficient protocol for N-formylation of various amines was carried out in the presence of immobilized sulfuric acid on silica gel (H2SO4-SiO2). All reactions were performed in refluxing triethyl orthoformate (65 °C). The product formamides were obtained with high-to-excellent yields within 4 min to 2 h. The current approach is advantageous, due to its short reaction time and high yields. The catalyst is recyclable with no significant loss in catalytic efficiency.

Design, Manufacturing, Characterization and Evaluation of Lipid Nanocapsules to Enhance the Biopharmaceutical Properties of Efavirenz.

Despite their incredible contribution to fighting viral infections, antiviral viral resistance is an increasing concern and often arises due to unfavorable physicochemical and biopharmaceutical properties. To address this kind of issue, lipid nanocapsules (LNC) are developed in this study, using efavirenz (EFV) as a drug model. EFV solubility was assessed in water, Labrafac Lipophile and medium chain triglycerides oil (MCT oil). EFV turned out to be more soluble in the two latter dissolving media (solubility > 250 mg/mL); hence, given its affordability, MCT oil was used for LNC formulation. LNC were prepared using a low-energy method named phase inversion, and following a design of experiments process. This one resulted in polynomial models that predicted LNC particle size, polydispersity index and zeta potential that were, respectively, around 50 nm, below 0.2 and below −33 mV, for the optimized formulations. Once synthesized, we were able to achieve an encapsulation efficacy of 87%. On the other hand, high EFV release from the LNC carrier was obtained in neutral medium as compared to acid milieu (pH 4) with, respectively, 42 and 27% EFV release within 74 h. Other characterization techniques were applied and further supported the successful encapsulation of EFV in LNCs in an amorphous form. Stability studies revealed that the developed LNC were quite stable over the period of 28 days. Ultimately, LNCs have been demonstrated to improve the biopharmaceutical properties of EFV and could therefore be used to fight against antiviral resistance.

A New Chalcone and Antimicrobial Chemical Constituents of Dracaena stedneuri.

Microbial infections are leading causes of death and morbidity all over the world due to the development of the resistance to antibiotics by certain microorganisms. In this study, the chemical exploration of the ethanol (EtOH) extract of the aerial part of Dracaena stedneuri (Dracaenaceae) led to the isolation of one previously unreported chalcone derivative, i.e., 2',4'-dihydroxy-2,3'-dimethoxychalcone (1), together with 12 known compounds: 8-(C)-methylquercetagetin-3,6,3'-trimethyl ether (2), methylgalangine (3), quercetin (4), kaempferol (5), 6,8-dimethylchrysin (6), ombuine-3-O-rutinoside (4',7-dimethylquercetin-3-O-α-L-rhamnopyranosyl-(1 → 6) -ß-D-glucopyranoside) (7), alliospiroside A (8), ß-sitosterol 3-O-glucopyranoside (9), ishigoside (10), betulinic acid (11), oleanolic acid (12), and lupeol (13). The structures were determined by spectroscopic and spectrometric analysis including 1- and 2-Dimensional Nuclear Magnetic Resonance (1D- and 2D-NMR), High-Resolution Electrospray Ionization Mass Spectrometry (HRESIMS), and comparison with literature data. The isolated secondary metabolites and crude extract displayed antibacterial activity against some multidrug-resistant strains with minimal inhibitory concentration (MIC) values ranging from 32 to 256 µg/mL. The antibacterial activity of compound 13 against Enterobacter aerogenes ATCC13048 (MIC value: 32 µg/mL) was higher than that of chloramphenicol used as the reference drug (MIC = 64 µg/mL).

A Critical Review of the Antimicrobial and Antibiofilm Activities of Green-Synthesized Plant-Based Metallic Nanoparticles.

Metallic nanoparticles (MNPs) produced by green synthesis using plant extracts have attracted huge interest in the scientific community due to their excellent antibacterial, antifungal and antibiofilm activities. To evaluate these pharmacological properties, several methods or protocols have been successfully developed and implemented. Although these protocols were mostly inspired by the guidelines from national and international regulatory bodies, they suffer from a glaring absence of standardization of the experimental conditions. This situation leads to a lack of reproducibility and comparability of data from different study settings. To minimize these problems, guidelines for the antimicrobial and antibiofilm evaluation of MNPs should be developed by specialists in the field. Being aware of the immensity of the workload and the efforts required to achieve this, we set out to undertake a meticulous literature review of different experimental protocols and laboratory conditions used for the antimicrobial and antibiofilm evaluation of MNPs that could be used as a basis for future guidelines. This review also brings together all the discrepancies resulting from the different experimental designs and emphasizes their impact on the biological activities as well as their interpretation. Finally, the paper proposes a general overview that requires extensive experimental investigations to set the stage for the future development of effective antimicrobial MNPs using green synthesis.

In vitro antibacterial and cytotoxic effects of Euphorbia grandicornis Blanc chemical constituents.

BACKGROUND: Euphorbia grandicornis is widely utilized in traditional medicine for the treatment of microbial infections including sexually transmitted diseases such as syphilis, gonorrhoea and for healing of wounds. OBJECTIVE: The aim of this work was to isolate and evaluate the antibacterial and anticancer activities of Euphorbia grandicornis chemical constituents. METHODS: Chemical constituents were isolated and identified using various spectroscopic techniques such as IR, MS, and NMR. The single point growth inhibitory potential of the compounds was determined using a 96-well plate based assay. RESULTS: The CH2Cl2 crude extracts exhibited potent antibacterial activity against Escherichia coli ATCC 8739 and Staphylococcus aureus ATCC 6538 with percentage growth of 94.90 ± 4.24 and 29.47 ± 4.89 respectively. Hence, the CH2Cl2 crude extract was further subjected to column chromatography which resulted in the isolation of methyl 2,5-dihydroxybenzoate (1), n-octyl benzoate (2), friedelanol (3), and germanicol (4) and identification of compounds 12-24 for the first time in the species based on the LC-MS/MS spectroscopic data. The purified compounds (1-4), and previously reported compounds (5-11) were evaluated for antibacterial activities against S. aureus and E. coli, as well as the cytotoxicity effects against HeLa cells. Of the purified compounds, methyl 2,5-dihydroxybenzoate (1), was the most active against E.coli and S. aureus with a percentage growth of 19.12 ± 0.65 and 23.32 ± 0.23 respectively. ß-amyrin (6), and ß-sitosterol (8), were active against S. aureus with percentage growth of 27.17 ± 0.07, and 47.79 ± 2.99 respectively. CONCLUSION: The results obtained from this study indicate that E. grandicornis, is a rich source of chemical constituents that may provide new lead compounds for the development of antibacterial agents.

Development of pH-Sensitive Chitosan-g-poly(acrylamide-co-acrylic acid) Hydrogel for Controlled Drug Delivery of Tenofovir Disoproxil Fumarate.

The present study aimed to develop a pH-sensitive chitosan-based hydrogel for controlled delivery of an anti-hepatitis B drug, tenofovir disoproxil fumarate (TDF). Free radical polymerization was utilized to graft acrylamide and acrylic acid using N,N-methylene bisacrylamide as the crosslinker. Physicochemical characterization confirmed the synthesis of thermally stable chitosan-g-poly(acrylamide-co-acrylic acid) hydrogels with well-defined pores within a fibrous surface. The prepared hydrogels exhibited pH and ionic strength sensitivity, with the swelling significantly lower under acidic and strong ionic strength conditions but higher in neutral and basic solutions. In addition, cytotoxicity studies on HeLa cell lines proved the cytocompatibility of the drug delivery material and its readiness for physiological applications. The encapsulation of TDF in the hydrogels was optimized and an encapsulation efficiency and a drug loading percentage of 96% and 10% were achieved, respectively. More interestingly, in vitro release studies demonstrated a pH-dependent release of TDF from hydrogels. The release at pH 7.4 was found to be up to five times higher than at pH 1.2 within 96 h. This further suggested that the newly developed hydrogel-loaded TDF could be proposed as a smart delivery system for oral delivery of anti-hepatitis B drugs.

Euphorbia Diterpenes: An Update of Isolation, Structure, Pharmacological Activities and Structure-Activity Relationship.

Euphorbia species have a rich history of ethnomedicinal use and ethnopharmacological applications in drug discovery. This is due to the presence of a wide range of diterpenes exhibiting great structural diversity and pharmacological activities. As a result, Euphorbia diterpenes have remained the focus of drug discovery investigations from natural products. The current review documents over 350 diterpenes, isolated from Euphorbia species, their structures, classification, biosynthetic pathways, and their structure-activity relationships for the period covering 2013-2020. Among the isolated diterpenes, over 20 skeletal structures were identified. Lathyrane, jatrophane, ingenane, ingenol, and ingol were identified as the major diterpenes in most Euphorbia species. Most of the isolated diterpenes were evaluated for their cytotoxicity activities, multidrug resistance abilities, and inhibitory activities in vitro, and reported good activities with significant half-inhibitory concentration (IC50) values ranging from 10-50 µM. The lathyranes, isopimaranes, and jatrophanes diterpenes were further found to show potent inhibition of P-glycoprotein, which is known to confer drug resistance abilities in cells leading to decreased cytotoxic effects. Structure-activity relationship (SAR) studies revealed the significance of a free hydroxyl group at position C-3 in enhancing the anticancer and anti-inflammatory activities and the negative effect it has in position C-2. Esterification of this functionality, in selected diterpenes, was found to enhance these activities. Thus, Euphorbia diterpenes offer a valuable source of lead compounds that could be investigated further as potential candidates for drug discovery.

Flavonoids from the Genus Euphorbia: Isolation, Structure, Pharmacological Activities and Structure-Activity Relationships.

Plants of the genus Euphorbia are widely distributed across temperate, tropical and subtropical regions of South America, Asia and Africa with established Ayurvedic, Chinese and Malay ethnomedical records. The present review reports the isolation, occurrence, phytochemistry, biological properties, therapeutic potential and structure-activity relationship of Euphorbia flavonoids for the period covering 2000-2020, while identifying potential areas for future studies aimed at development of new therapeutic agents from these plants. The findings suggest that the extracts and isolated flavonoids possess anticancer, antiproliferative, antimalarial, antibacterial, anti-venom, anti-inflammatory, anti-hepatitis and antioxidant properties and have different mechanisms of action against cancer cells. Of the investigated species, over 80 different types of flavonoids have been isolated to date. Most of the isolated flavonoids were flavonols and comprised simple O-substitution patterns, C-methylation and prenylation. Others had a glycoside, glycosidic linkages and a carbohydrate attached at either C-3 or C-7, and were designated as d-glucose, l-rhamnose or glucorhamnose. The structure-activity relationship studies showed that methylation of the hydroxyl groups on C-3 or C-7 reduces the activities while glycosylation loses the activity and that the parent skeletal structure is essential in retaining the activity. These constituents can therefore offer potential alternative scaffolds towards development of new Euphorbia-based therapeutic agents.

Review of the Traditional Uses, Phytochemistry, and Pharmacological Activities of Rhoicissus Species (Vitaceae).

Species within the genus Rhoicissus (Vitaceae) are commonly used in South African traditional medicine. The current review discusses the occurrence, distribution, traditional uses, phytochemistry, and pharmacological properties of Rhoicissus species covering the period 1981-2020. The data reported were systematically collected, read, and analysed from scientific electronic databases including Scopus, Scifinder, Pubmed, and Google Scholar. Reported evidence indicates that species in this genus are used for the treatment of gastrointestinal complaints, sexually transmitted infections (STIs), and infertility, as well as to tone the uterus during pregnancy and to facilitate delivery. Pharmacological studies have further shown that members of the Rhoicissus genus display antidiabetic, uterotonic, ascaricidal, hepatoprotective, antioxidant, antimicrobial, anticancer, and anti-inflammatory properties. They are linked to the presence of bioactive compounds isolated from the genus. Hence, Rhoicissus species can potentially be an alternative therapeutic strategy to treat diseases and develop safer and more potent drugs to combat diseases. Plant species of this genus have valuable medicinal benefits due to their significant pharmacological potential. However, scientific investigation and information of the therapeutic potential of Rhoicissus remain limited as most of the species in the genus have not been fully exploited. Therefore, there is a need for further investigations to exploit the therapeutic potential of the genus Rhoicissus. Future studies should evaluate the phytochemical, pharmacological, and toxicological activities, as well as the mode of action, of Rhoicissus crude extracts and secondary compounds isolated from the species.

Unlocking the Diversity of Pyrroloiminoquinones Produced by Latrunculid Sponge Species.

Sponges of the Latrunculiidae family produce bioactive pyrroloiminoquinone alkaloids including makaluvamines, discorhabdins, and tsitsikammamines. The aim of this study was to use LC-ESI-MS/MS-driven molecular networking to characterize the pyrroloiminoquinone secondary metabolites produced by six latrunculid species. These are Tsitsikamma favus, Tsitsikamma pedunculata, Cyclacanthia bellae, and Latrunculia apicalis as well as the recently discovered species, Tsitsikamma nguni and Tsitsikamma michaeli. Organic extracts of 43 sponges were analyzed, revealing distinct species-specific chemical profiles. More than 200 known and unknown putative pyrroloiminoquinones and related compounds were detected, including unprecedented makaluvamine-discorhabdin adducts and hydroxylated discorhabdin I derivatives. The chemical profiles of the new species T. nguni closely resembled those of the known T. favus (chemotype I), but with a higher abundance of tsitsikammamines vs. discorhabdins. T. michaeli sponges displayed two distinct chemical profiles, either producing mostly the same discorhabdins as T. favus (chemotype I) or non- or monobrominated, hydroxylated discorhabdins. C. bellae and L. apicalis produced similar pyrroloiminoquinone chemistry to one another, characterized by sulfur-containing discorhabdins and related adducts and oligomers. This study highlights the variability of pyrroloiminoquinone production by latrunculid species, identifies novel isolation targets, and offers fundamental insights into the collision-induced dissociation of pyrroloiminoquinones.

Green synthesis of antimicrobial silver nanoparticles using aqueous leaf extracts from three Congolese plant species (Brillantaisia patula, Crossopteryx febrifuga and Senna siamea).

In the present study, silver nanoparticles (AgNPs) were synthesized using aqueous leaf extracts of three Congolese plant species, namely Brillantaisia patula (BR-PA), Crossopteryx febrifuga (CR-FE) and Senna siamea (SE-SI). The obtained AgNPs were studied for their optical, structural, surface morphological and antibacterial properties. The prepared AgNPs were characterized by using UV-Visible spectra, Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR), X-ray spectroscopy (EDX) and X-ray diffractometer (XRD). The synthesized nanoparticles were spherical shaped and well-dispersed with average sizes ranging from 45 to 110 nm. The AgNPs derived from BR-PA, CR-FE and SE-SI exhibited higher antibacterial activity against three bacterial pathogens of the human skin compared to their respective crude extracts and AgNO3. This indicated that the biomolecules covering the nanoparticles may enhance the biological activity of metal nanoparticles. Hence, our results support that biogenic synthesis of AgNPs from Congolese plants constitutes a potential area of interest for the therapeutic management of microbial diseases such as infectious skin diseases.

Antiparasitic Constituents of Beilschmiedia louisii and Beilschmiedia obscura and Some Semisynthetic Derivatives (Lauraceae).

The MeOH/CH2Cl2 (1:1) extracts of the roots and leaves of Beilschmiedia louisii and B. obscura showed potent antitrypanosomal activity during preliminary screening on Trypanosoma brucei brucei. Phytochemical investigation of these extracts led to the isolation of a mixture of two new endiandric acid derivatives beilschmiedol B (1) and beilschmiedol C (2), and one new phenylalkene obscurene A (3) together with twelve known compounds (4-15). In addition, four new derivatives (11a-11d) were synthesized from compound 11. Their structures were elucidated based on their NMR and MS data. Compounds 5, 6, and 7 were isolated for the first time from the Beilschmiedia genus. Additionally, the NMR data of compound 4 are given here for the first time. The isolates were evaluated for their antitrypanosomal and antimalarial activities against Tb brucei and the Plasmodium falciparum chloroquine-resistant strain Pf3D7 in vitro, respectively. From the tested compounds, the mixture of new compounds 1 and 2 exhibited the most potent antitrypanosomal activity in vitro with IC50 value of 4.91 µM.