Psorospermun febrifugum is used to treat a wide range of diseases, amongst which are malaria, pneumonia, skin diseases, dysmenorrhoea, dysentery, and tuberculosis. This study aimed to investigate the cytotoxicity of the methanol extract from the fruits of P. febrifugum (PFF) and its toxicological profile on Wistar rats. the cytotoxicity of the extract, fractions, and the isolated compound, harungine anthrone (1), was evaluated using the resazurin reduction assay (RRA). Acute and subchronic toxicity studies were conducted according to the experimental protocol the Organisation for Economic Cooperation and Development (OECD) described. PFF, the fractions PFFa, PFFb, PFFc, and PFFd were cytotoxic (IC50 below 20 mu g/mL) towards at least one of the 9 tested cancer cell lines. The best cytotoxic effects (IC50 below 5 mu g/mL) were obtained with the PFFb fraction against CCRF-CEM leukemia cells (1.55 mu g/mL) and its multidrug-resistant subline CEM/ ADR5000 (4.28 mu g/mL), as well as MDA-MB-231-pcDNA breast adenocarcinoma cells (3.38 mu g/mL). Compound 1 had moderate activity with IC50 values ranging from 26.14 mu M (against HCT116 (p53*/*) colon adenocarcinoma cells) to 34.18 mu M (against U87.MG glioblastoma cells. In the acute toxicity study, no deaths or signs of toxicity were recorded at 5,000 mg/kg body weight (b.w.) of rats. Subchronic toxicity studies of PFF showed some changes in biochemical parameters, including serum levels of low-density lipoproteins (LDL), high-density lipoproteins (HDL), and transaminases at 250, 500, and 1000 mg/kg b.w. Histopathological analysis of the liver and kidney did not reveal any damage in treated animals compared to controls. In conclusion, the crude extract of P. febrifugum is a source of cytotoxic drugs. It is almost safe in acute and prolonged oral administrations at doses lower than 1,000 mg/kg b.w. However, it should be taken cautiously regarding its effect on the rat's body and biochemical parameters. (c) 2025 SAAB. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Polyscias fulva (Hiern) Harms. (Araliaceae) is a medicinal plant used in the treatment of various types of illness including infectious diseases and cancers. The present chapter aimed at compiling the ethnopharmacological uses, the phytochemistry, and the cytotoxicity of this plant. P. fulva has many pharmacological properties including antioxidant, anti-inflammatory, antivenereal, antibacterial, antifungal, and anticancer activities. Botanicals from this plant had cytotoxic effects on several human cancer cell lines, including multidrug-resistant phenotypes such as P-glycoprotein overexpressing CEM/ADR5000 leukemia cells, breast cancer resistance protein-transfected (BCRP) MDA-MB-231-BCRP breast cancer cells, Tumor suppressor p53 knockout cells (HCT116 p53(-/)-) colon cancer cells, and mutation-activated epidermal growth factor receptor-transfected U87MG.Delta EGFR glioblastoma cells. P. fulva selectively showed antiproliferative effects against breast, prostate, colon, lung, stomach, and ovarian cancer, and hematological cancer cell lines. The cytotoxic phytochemicals identified in this plant include oleanolic acid, alpha-hederin, quercetin, beta-sitosterol, and beta-sitosterol-beta-(D)-glucoside. Finally, P. fulva as well as its constituents may be useful in the development of novel drugs to fight cancer including the refractory phenotypes.

Background Cancer remains a global health concern and constitutes an important barrier to increasing life expectancy. Malignant cells rapidly develop drug resistance leading to many clinical therapeutic failures. The importance of medicinal plants as an alternative to classical drug discovery to fight cancer is well known. Brucea antidysenterica is an African medicinal plant traditionally used to treat cancer, dysentery, malaria, diarrhea, stomach aches, helminthic infections, fever, and asthma. The present work was designed to identify the cytotoxic constituents of Brucea antidysenterica on a broad range of cancer cell lines and to demonstrate the mode of induction of apoptosis of the most active samples. Methods Seven phytochemicals were isolated from the leaves (BAL) and stem (BAS) extract of Brucea antidysenterica by column chromatography and structurally elucidated using spectroscopic techniques. The antiproliferative effects of the crude extracts and compounds against 9 human cancer cell lines were evaluated by the resazurin reduction assay (RRA). The activity in cell lines was assessed by the Caspase-Glo assay. The cell cycle distribution, apoptosis via propidium iodide (PI) staining, mitochondrial membrane potential (MMP) through 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining, and the reactive oxygen species (ROS) via 2´,7´-dichlorodihydrofluoresceine diacetate (H2DCFH-DA) staining, were investigated by flow cytometry. Results Phytochemical studies of the botanicals (BAL and BAS) led to the isolation of seven compounds. BAL and its constituents 3, (3-(3-Methyl-1-oxo-2-butenyl))1 H indole ( 1 ) and hydnocarpin ( 2 ), as well as the reference compound, doxorubicin, had antiproliferative activity against 9 cancer cell lines. The IC 50 values varied from 17.42 µg/mL (against CCRF-CEM leukemia cells) to 38.70 µg/mL (against HCT116 p53 −/− colon adenocarcinoma cells) for BAL, from 19.11 µM (against CCRF-CEM cells) to 47.50 µM (against MDA-MB-231- BCRP adenocarcinoma cells) for compound 1 , and from 4.07 µM (against MDA-MB-231- pcDNA cells) to 11.44 µM (against HCT116 p53 + / + cells) for compound 2 . Interestingly, hypersensitivity of resistant cancer cells to compound 2 was also observed. BAL and hydnocarpin induced apoptosis in CCRF-CEM cells mediated by caspase activation, the alteration of MMP, and increased ROS levels. Conclusion BAL and its constituents, mostly compound 2 , are potential antiproliferative products from Brucea antidysenterica . Other studies will be necessary in the perspective of the discovery of new antiproliferative agents to fight against resistance to anticancer drugs.

In the present chapter, the overview of active botanicals and phytochemicals of the flora of Africa against drug-sensitive and drug-resistant strains of Pseudomonas aeruginosa has been provided. Using the data obtained from the crude extracts of up to 182 plants and 135 derived molecules, the rationale cutoff points for the classification of antibacterial agents from natural sources against Enterobacteria were established. i) For botanicals: outstanding activity when MIC <= 32 mu g/mL; excellent activity when 32 < MIC <= 128 mu g/mL; very good activity when 128 < MIC <= 256 mu g/mL; good activity when 256 < MIC <= 512 mu g/mL, average activity when 512 < MIC <= 1024 mu g/mL, weak activity or not active when MIC values > 1024 mu g/mL. ii) For phytochemicals: outstanding activity when MIC <= 4 mu g/mL, excellent activity when 4 < MIC <= 32 mu g/mL; very good activity when 32 < MIC <= 128 mu g/mL, good activity when 128 < MIC <= 256 mu g/mL, average activity when 256 < MIC <= 512 mu g/mL, weak activity or not active when MIC values > 512 mu g/mL. On these bases, we have identified 19 most active plants, as well as 13 most promising antibacterial phytochemicals acting on the documented Enterobacteria. Other plants amongst which Harungana madagascariensis, Zingiber officinale, Petroselinum crispum, Apium graveolens, Ocimum basilicum, Gnetum africanum Capsicum annuum, as well as compounds such as beta-sitosterol 3-O-beta-(D)-glucopyranoside, palmatin, isobavachalcone, and diospyrone were identified as potential antibacterial agents if they are combined with efflux pumps inhibitors.

Bauhinia thonningii is a plant traditionally used against many human diseases such as gastric ulcers, fever, inflammations, coughs, dysentery, diarrhea, and malaria. In the present investigation, the cytotoxicity of methanol extract of Bauhinia thonningii leaves (BTL), fractions and the isolated phytoconstituents was determined in a panel of 9 human cancer cell lines including drug sensitive and multidrug-resistant (MDR) phenotypes. The acute and sub-chronic oral toxicity of BTL was investigated as well. Compounds were isolated using chromatographic techniques while their chemical structures were determined using spectroscopic methods. The resazurin reduction assay (RRA) was used to evaluate the cytotoxicity of samples, propidium iodide (PI) for apoptosis, 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining for mitochondrial membrane potential (MMP) analysis, 2´,7´-dichlorodihydrofluoresceine diacetate (H2DCFH-DA) staining for the quantification of reactive oxygen species (ROS), whereas Caspase Glo assays were combined by means of flow cytometry. Furthermore, the toxicological investigations were performed as recommended by the Organization for Economic Cooperation and Development (OECD). The botanicals as well as 6-C-methylquercetin-3,7-dimethyl ether (2), quercetin-3-O-L-rhamnopyranoside (5), quercetin-3-O-β-glucopyranoside (6), 6,8-C-dimethylkaempferol 3,7-dimethyl ether (7), and 6,8-C-dimethylkaempferol-3-methyl ether (8) had promising cytotoxic effects in the 9 tested cancer cell lines. The IC50 values below 20 µg/mL (botanicals) or 10 µM (compounds) on at least 1/9 tested cancer cell lines were considered. The best cytotoxic effects with IC50 values below 5 µM were achieved with compounds 7 against CEM/ADR5000 leukemia cells (2.86 µM) and MDA-MB-231-pcDNA breast adenocarcinoma cells (1.93 µM) as well as 8 against CCRF-CEM leukemia cells (3.03 µM), CEM/ADR5000 cells (2.42 µM), MDA-MB-231-pcDNA (2.34 µM), and HCT116 p53−/− cells (3.41 µM). BTL and compound 8 induced apoptotic cell death in CCRF-CEM cells through caspase activation, alteration of MMP, and increased ROS production. BTL did not cause any adverse effects in rats after a single administration at 5000 mg/kg or a repeated dose of 250 mg/kg body weight (b. w.). Bauhinia thonningii and its constituents are sources of cytotoxic drugs that deserve more in-depth studies to develop novel antiproliferative phytomedicine to fight cancer including resistant phenotypes.

Background: The antibiotic resistance of pathogenic bacteria is one of the major health problems worldwide. The development of novel antimicrobial therapies based on natural products that greatly reduce this resistance is urgent. The present study aimed at evaluating the antimicrobial potential of four animal methanol extracts, Gryllus campestris, Testudo hermanni, Cardisoma guanhumi, and Rhinella jimi as well as their synergistic effects with antibiotics against twenty Gram-negative bacteria. Methods: Zoochemical analysis of extracts was performed using qualitative reference methods for the detection of secondary metabolites and the ninhydrin reaction for the detection of protein constituents. The antibacterial activity of animal extracts alone and in combination with antibiotics was carried out using broth microdilution methods. Results: Amino acids, peptides, or proteins were present in all extracts. Alkaloids were detected in extracts of C. guanhumi and R. jimi and were absent in other extracts. Flavonoids, tannins, and steroids were evidenced only in dried and fresh extracts of R. jimi. Polyphenols, anthocyanins, anthraquinones, and saponins were not detected in all extracts. Dried extract from R. jimi was most active. It had antibacterial potential against 85% of the tested bacterial strains with significant activity (100≤MIC≤512 µg/mL) against 35% of bacteria; this included three E. coli (ATCC8739, AG100ATet and MC4100), one E. aerogenes (ATCC13048), one K. pneumoniae (ATCC11296) and two P. aeruginosa (PA01 and PA124). Dried and fresh extracts from C. guanhumi displayed an antibacterial activity against 40% and 20% of the bacteria tested, respectively, whereas dried extracts from G. campestris and fresh extracts from T. hermanni inhibited the growth of 15% and 10% of bacteria, respectively (MIC range of 512 to 2048 µg/mL). The dried and fresh extracts of R. jimi, at MIC/2 and MIC/4, potentialized the activities of more than 70% of the antibiotics respectively against more than 70% of studied bacteria. Both extracts highly improved the activity of oxacillin, gentamicin, erythromycin, and ciprofloxacin with improved activity factors (IAFs) ranging from 16 to 256. Conclusion: This work demonstrated that R. jimi extracts had a broad spectrum of antibacterial activities. The overall data provided evidence that animals investigated in this study might be potential sources of natural antimicrobial agents; They can be combined with clinically used antibiotics to overcome bacterial resistance. Keywords: Animal extract, antibiotics; Gram-negative bacteria; efflux pumps; multidrug resistance; Rhinella jimi.

The cytotoxic potential of a naturally occurring indoloquinazoline alkaloid, soyauxinium chloride (SCHL), was determined on a broad panel of animal and human cancer cell lines, including various sensitive and drug-resistant phenotypes. The cytotoxicity, SCHL-induced autophagic, ferroptotic, and necmptotic cell death were evaluated by the resazurin reduction assay (RRA). Caspase-Glo assay was used to detect the activity of caspases using spectrophotometric analysis. Flow cytometry was applied for cell cycle analysis (PI staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP) (JC-1) and reactive oxygen species (ROS) (H2DCFH-DA). SCHL and doxorubicin (reference molecule) exhibited cytotoxic effects towards the 18 cancer cell lines tested. The IC50 values obtained ranged from 3.64 mu M (towards CCRF-CEM leukemia cells) to 16.86 mu M (against the BRAF-wildtype SKMe1-505 melanoma cells for SCHL). Collateral sensitivity of the resistant HCT116 p53(-/-) colon adenocarcinoma cells to SCHL was observed as well as the normal sensitivity of CEM/ADR5000 leukemia cells, MDA-MB-231-BCRP breast adenocarcinoma cells and U87. MG Delta EGFR glioblastoma cells. SCHL induced apoptosis in CCRF-CEM cells via caspases 3/7-, 8- and 9-activation, MMP alteration and increased ROS production, and otherwise ferroptosis and necroptosis. SCHL is a prominent cytotoxic alkaloid that should be further studied to develop a novel drug to combat cancers including refractory phenotypes.

Ethnopharmacological relevance: Piper capense is a medicinal spice whose fruits are traditionally used as aqueous decoction to heal several ailments such as trypanosomiasis, helminthic infections, and cancer. Aim of the study. (1) To perform phytochemical investigation of the methanol extract of Piper capense; (2) to evaluate the cytotoxicity of botanicals (PCF, fractions PCFa-e), isolated phytochemicals on a broad panel of animal and human cancer cell lines; (3) to evaluate the induction of apoptosis of the most active samples. Material and methods: Resazurin reduction assay (RRA) was used to determine the cytotoxicity of the studied samples. Cell cycle distribution (PI staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP; JC-1) and reactive oxygen species (ROS; H2DCFH-DA) were measured by flow cytometry. Column chromatography (CC) was used for the purification of PCF, whilst nuclear magnetic resonance (NMR) spectroscopic and mass spectrometric (MS) analyses were applied for structural elucidation. Results: The phytochemical investigation of PCF led to the isolation of 11 compounds: licarin B (1), licarin A (2), 7-(1,3-benzodioxol-5-yl)-7,8-dihydro-8-methyl-5-(2-propenyl)-furo [3,2-e]-1,3-benzodioxole (3), nitidine isocyanate (4), 5-hydroxy-7,4'-dimethoxyflavone (5), cardamomin (6), sitosteml (7) and stigmasteml (8), beta-sitosterol 3-O-beta-D-glucopyranoside (9), oleanolic acid (10) and lupeol (11). Fraction PCFb, compound 2 and doxorubicin (as positive control drug) revealed cytotoxic effects towards the 18 tested cancer cell lines. The IC50 values ranged from 6.1 mu g/mL (against CCRF-CEM cells) to 44.2 mu g/mL (against BRAF-V600E homozygous mutant melanoma cells) for PSCb; from 4.3 mu M (against CCRF-CEM cells) to 21.8 mu M (against HCT116 p53(-/-)) for compound 2 and from 0.02 mu M (against CCRF-CEM cells) to 123.0 mu M (against CEM/ADR5000 cells) for doxorubicin. PCFb and compound 2 induced apoptosis in CCRF-CEM cells mediated by activation of caspase 3/7, 8 and 9, MMP alteration and increased ROS production. Conclusion: Piper capense is a source of potent cytotoxic botanicals and phytochemicals that could help to fight various types of cancer including multidrug resistance phenotypes. PCFb and compound 2 should further be explored to develop new drugs to fight malignancies.

Background: The rapid emergence of multidrug resistant (MDR) bacteria is occurring worldwide, endangering the efficacy of antibiotics, which have transformed medicine and saved millions of lives. Antibiotic-resistant infections are already widespread in the Sub-Saharan Africa and across the globe. To extend the search for new and more efficient antimicrobial drugs from natural sources, this work has been carried out to study the phytochemical composition and the antibacterial activities of some Cameroonian dietary plants (Cocos nucifera, Glycine max and Musa sapientum) against several MDR Gram-negative strains including Escherichia coli, Enterobacter aerogenes, Providencia stuartii, Klebsiella pneumoniae, Pseudomonas aeruginosa species expressing efflux pumps. Methods: Phytochemical screening of plant extracts was performed using qualitative standard methods and the antimicrobial assays of these extracts alone and in combination with antibiotics were done using serial 96-wells microplate dilution essays. Results: Each plant extract contained at least three mean classes of secondary metabolites. Glycine max, epicarps, leaves and bark of C. nucifera as well as mesocarps of M. sapientum contained each alkaloids, polyphenols, flavonoids, and triterpenes. Moreover, steroids were also found in G. max, steroids and saponins in epicarps and saponins in bark of C. nucifera. Meanwhile epicarps from M. sapientum contained only polyphenols, flavonoids and saponins. Antibacterial assays showed that different parts of C. nucifera were more active than other extracts. Their minimal inhibitory concentrations (MICs) varied from 128 to 2048 µg/mL. The bark part presented the highest antibacterial potential inhibiting the growth of 90% of strains with significant activity (100≤MIC≤512 µg/mL) against 50% of them (three E. coli, four E. aerogenes and three K. pneumoniae). It showed bactericidal effects (MBC/MIC≤4) on 45% of the same bacterial species. It was followed by epicarps and leaves parts which exhibited an inhibitory power against 75% and 60% of bacteria with significant activity on 40% and 20% of them respectively. They also showed bactericidal effects on E. coli ATCC8739 for epicarps extract and E. coli ATCC8739 and P. stuartii NEA16 for leaves extract. Extracts from G. max were less active and those from mesocarps and epicarps of M. sapientum did not showed any activity on all studied bacteria. Bark and epicarps extracts of C. nucifera potentiated the activities of all used antibiotics against at least 70% of bacteria while leaves extract exhibited this effect improving the activities of 67% of antibiotics with improvement activity factors (IAF) ranging from 2 to 256 suggesting that they contain bioactive compounds which could be considered as efflux pumps inhibitors. Extracts from G. max, epicarps and mesocarps of M. sapientum enhanced the inhibitory potential of 56%, 34% and 23% of antibiotics respectively against at least 70% of studied bacteria. These increases of activities also characterize synergistic effects between antibiotics and bioactive compounds of plants. Conclusion: The findings of this work suggest that infections by resistant bacteria can be treated using different parts of C. nucifera as an alternative to commonly used antibiotics.

The global cancer burden remains a serious concern with the alarming incidence of one in eight men and one in eleven women dying in developing countries. This situation is aggravated by the multidrug resistance (MDR) of cancer cells that hampers chemotherapy. In this study, the cytotoxicity of the methanol extract (HRB), fractions (HRBa, HRBb, and HRBa1-5), and compounds from the bark of Hypericum roeperianum (HRB) was evaluated towards a panel of 9 cancer cell lines. The mode of action of the HRB and trichadonic acid (1) was also studied. Column chromatography was applied to isolate the constituents of HRB. The cytotoxicity of botanicals and phytochemicals was evaluated by the resazurin reduction assay (RRA). Caspase-Glo assay was used to evaluate the activity of caspases, and reactive oxygen species (ROS) (H2DCFH-DA) were assessed by flow cytometry. Phytochemicals isolated from HRB were trichadonic acid (1), fridelan-3-one (2), 2-hydroxy-5-methoxyxanthone (3), norathyriol (4), 1,3,5,6-tetrahydroxyxanthone (5), betulinic acid (6), 3′-hydroxymethyl-2′-(4″-hydroxy-3″,5″-dimethoxyphenyl)-5′,6′:5,6-(6,8-dihydroxyxanthone)-1′,4′-dioxane (7), and 3′-hydroxymethyl-2′-(4″-hydroxy-3″,5″-dimethoxyphenyl)-5′,6′:5,6-(xanthone)-1′,4′-dioxane (8). Botanicals HRB, HRBa, HRBa2-4, HRBb, and doxorubicin displayed cytotoxic effects towards the 9 tested cancer cell lines. The recorded IC50 values ranged from 11.43 µg/mL (against the P-glycoprotein (gp)-overexpressing CEM/ADR5000 leukemia cells) to 26.75 µg/mL (against HCT116 (p53+/+) colon adenocarcinoma cells) for the crude extract HRB. Compounds 1, 5, and doxorubicin displayed cytotoxic effects towards the 9 tested cancer cell lines with IC50 values varying from 14.44 µM (against CCRF-CEM leukemia cells) to 44.20 µM (against the resistant HCT116 (p53−/−) cells) for 1 and from 38.46 µM (against CEM/ADR5000 cells) to 112.27 µM (against the resistant HCT116 (p53−/−) cells) for 5. HRB and compound 1 induced apoptosis in CCRF-CEM cells. The apoptotic process was mediated by enhanced ROS production for HRB or via caspases activation and enhanced ROS production for compound 1. This study demonstrated that Hypericum roeperianum is a potential source of cytotoxic phytochemicals such as trichadonic acid and could be further exploited in cancer chemotherapy.

Abstract Background: Bacterial infections involving the multidrug resistant (MDR) strains are among the top leading causes of death throughout the world. Healthcare system across the globe has been suffering from an extra-ordinary burden in terms of looking for the new and more potent antimicrobial compounds. The aim of the present study was to determine the antibacterial activity of some Cameroonian edible plants (Garcinia lucida bark, Phoenix dactylifera pericarps, Theobroma cacao pod, Solanum macrocarpon leaves and Termitomyces titanicus whole plant) and their antibiotics-potentiation effects against some MDR Gram-negative bacteria phenotypes expressing efflux pumps (Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa and Providencia stuartii strains). Methods: The antibacterial activities of plant extract alone and in combination with usual antibiotics were carried out using the micro-dilution method. The effects of the most active plant extract (Garcinia lucida bark) on H+-ATPase-mediated proton pumps and on bacterial growth kinetic were performed using experimental protocols, while qualitative reference methods were used to highligh the major groups of secondary metabolites present in the extracts. Results: Qualitative phytochemical screening of plant extracts indicated that all analysed secondary metabolites were present in Theobroma cacao and Termitomyces titanicus while one (saponins) of them was absent in Garcinia lucida and Solanum macrocarpon. Only three of them (polyphenols, flavonoids and saponins) were detected in Phoenix dactylifera. Antibacterial essays showed that G. lucida was the most active plant as it inhibited the growth of all studied bacteria with strong activity (MIC<100 µg/mL) against E. coli ATCC8739, significant activity (100≤MIC≤512 µg/mL) against 80% of bacteria and moderate activity (512

Abstract Background: In recent years, drug resistance to human pathogenic bacteria has been commonly reported from all over the world. As antimicrobial activities of most medicinal plants and antibiotics have been already explored, it is more important to make investigations on animal species mainly invertebrates which could constitute an efficient source of antimicrobial molecules. This work was aimed at contributing to the fight against microbial resistance through the study of antibacterial potential of three animal species (Helix aspersa, Bitis arietans, Aristaeomorpha foliacea) on several multidrug-resistant (MDR) Gram-negative strains overexpressing efflux pumps including Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa. Methods: The microdilution technique was used to evaluate the antibacterial activities of the tested samples by determining their minimal inhibitory concentrations (MICs), as well as the effect of their combination with antibiotics. Studies on the mechanisms of action of the most active sample, dried Bitis arietans extract, was carried out using standard methods for evaluating the effects of this extract on bacterial H+-ATPases-mediated proton pumps and on bacterial growth kinetics. In this latter case, the optical density was read spectrophotometrically. Results: Zoochemical screening indicated the presence of protein constituents and alkaloids and the absence of other metabolites in all tested extracts. Dried B. arietans showed the best antibacterial activity by inhibiting the growth of 90% of studied bacterial strains with MICs ranging from 128 to 2048 μg/ml. Moreover, this extract presented a significant activity (100≤MIC≤512 µg/ml) against 35% of bacteria that are E. coli (ATCC8739, AG100ATet, MC4100), E. aerogenes EA27, K. pneumoniae ATCC11296, P. aeruginosa (PA01, PA124) and a moderate activity (512

Background Multidrug-resistant (MDR) bacteria remain a major cause of morbidity and mortality globally. The present study was designed to investigate the in vitro antibacterial activities of crude methanol extract and constituents isolated by Column Chromatography (CC) from Cassia sieberiana bark (CSB) against ten MDR Gram-negative bacteria, as well as the mechanisms of action of the most active sample. Methods The antibacterial activity of the tested samples (extract, the fractions and their compounds isolated by CC and the structures obtained by exploiting 1 H and 13 C Nuclear magnetic resonance (NMR) spectra) in the presence and absence of an efflux pumps inhibitor, phenylalanine-arginine β-naphthylamide (PAβN), was evaluated using the micro-dilution method. The effects of the most active sample were evaluated on the cell growth kinetic and on the bacterial H + -ATPase proton pumps. Results Phytochemical composition of the crude extract showed a rather selective distribution of secondary metabolites (presence of polyphenols, tannins, steroids, triterpenes, flavonoids, alkaloids, saponins and absence of anthocyanins, anthraquinones). The tested samples displayed different antibacterial activities with minimal inhibitory concentrations (MICs) ranging from 64 to 512 μg/mL. Crude extract (CS) and fraction CSc showed the highest inhibitory spectra, both inhibiting all of the studied bacteria except Enterobacter aerogenes EA27 strain. Fraction CSc exerted bactericidal effects on most bacteria meanwhile, crude extract (CS) and sub-fraction CSc2 exerted bacteriostatic effects. Compounds 1 (spectaline) and 2 (iso-6-cassine) inhibited the growth of 70% ( Escherichia coli ATCC8739 and AG102, Klebsiella pneumoniae ATCC11296, Enterobacter aerogenes ATCC13048 and EA27, Providencia stuartii ATCC29916, Pseudomonas aeruginosa PA01) and 60% ( Escherichia coli ATCC8739, Klebsiella pneumoniae ATCC11296 and KP55, Providencia stuartii ATCC29916, Pseudomonas aeruginosa PA01 and PA124) of bacteria respectively with MICs ranging from 128 to 512 μg/mL. In the presence of PAβN, the activities of crude extract CS, fraction CAc and sub-fraction CSc2 strongly increased on most bacteria strains as their MICs significantly decreased. Sub-fraction CSc2 inhibited the H + -ATPase proton pumps and altered growth kinetic of Escherichia coli ATCC8739. Conclusion The overall results justify the traditional use of C. sieberiana for the treatment of bacterial infections.

Background: Recalcitrant cancers appear as a major obstacle to chemotherapy, prompting scientists to intensify the search for novel drugs to tackle the cell lines expressing multi-drug resistant (MDR) phenotypes. Purpose: The purpose of this study was to evaluate the antiproliferative potential of a ferrulic acid derivative, 8,8-bis-(dihydroconiferyl)-diferulate (DHCF2) on a panel of 18 cancer cell lines, including various sensitive and drug-resistant phenotypes, belonging to human and animals. The mode of induction of cell death by this compound was further studied. Methods: The antiproliferative activity, autophagy, ferroptotic and necroptotic cell death were evaluated by the resazurin reduction assay (RRA). CCRF-CEM leukemia cells were used for all mechanistic studies. A caspase-Glo assay was applied to evaluate the activity of caspases. Cell cycle analysis (PI staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP) (JC-1) and reactive oxygen species (ROS) (H2DCFH-DA) were assessed by flow cytometry. Results: DHCF2 demonstrated impressive cytotoxic effects towards the 18 cancer cell lines tested, with IC50, values all below 6.5 mu M. The obtained IC50 values were in the range of 1.17 mu M (towards CCRF-CEM leukemia cells) to 6.34 mu M (towards drug-resistant HCT116 p53(-/- )human colon adenocarcinoma cells) for DHCF2 and from 0.02 mu M (against CCRF-CEM cells) to 122.96 mu M (against multidrug-resistant CEM/ADR5000 leukemia cells) for the reference drug, doxorubicin. DHCF2 had IC50, values lower than those of doxorubicin, against CEM/ADR5000 cells and on some melanoma cell lines, such as MaMel-80a cells, Mel-2a cells, MV3 cells and SKMel-505 cells. DHCF2 induced autophagy as well as apoptosis in CCRF-CEM cells though caspases activation, MMP alteration and increase of ROS production. Conclusion: The studied diferulic acid, DHCF2, is a promising antiproliferative compound. It deserves further indepth investigations with the ultimate aim to develop a novel drug to fight cancer drug resistance.

Ethnopharmacological relevance: Araliopsis soyauxii Engl. (Rutaceae) is a Cameroonian medicinal plant traditionally used to treat lung diseases, malaria, and gonorrhea. It has been demonstrated that infectious disease contribute to about 20% of all human tumours. Aims of the study: (1) To perform a phytochemical investigation of the dichloromethane-methanol 1:1 extracts of the bark (ASB), roots (ASR), and leaves (ASL) from Araliopsis soyauxii; (2) to evaluate the cytotoxicity of extracts and isolated compounds; (3) to determine the mode of induction of apoptosis of ASB and kihadanin B (12). Materials and methods: Fourteen constituents of the crude extracts were isolated by column chromatography, while spectroscopic techniques were used for structural elucidation. The resazurin reduction assay (RRA) was applied to determine the cytotoxicity of samples towards a panel of 9 cancer cell lines. For caspases activity, the Caspase-Glo assay was used; flow cytometry was applied to investigate the cell cycle distribution (PI staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP; JC-1 staining), and the reactive oxygen species (ROS; H2DCFH-DA staining). Results: Phytochemical investigations of botanicals (ASB, ASR, and ASL) led to the isolation of 14 compounds. Extract ASB, obacunone (11), kihadanin B (12) as well as doxorubicin (control drug) revealed cytotoxicity towards the 9 cancer cell lines tested. The IC50 values ranged from 11.11 mu g/mL (against CCRF-CEM leukemia cells) to 28.18 mu g/mL (against HCT116 p53(+/+) colon adenocarcinoma cells) for ASB; from 28.25 mu M (against MDA-MB-231-pcDNA breast adenocarcinoma cells) to 65.13 mu M (against HepG2 hepatocarcinoma cells) for compound 11, and from 5.77 mu M (against CCRF-CEM cells) to 43.56 mu M (against U87.MG Delta EGFR glioblastoma cells) for compound 12. ASB and compound 12 induced apoptosis in CCRF-CEM cells. ASB induced the apoptotic process mediated by MMP alteration and enhanced ROS production, while compound 12 induced apoptosis by caspases activation, MMP alteration, and enhanced ROS production. Conclusion: This study demonstrated that Araliopsis soyauxii is a potential source of cytotoxic phytochemicals such as kihadanin B and that ASB and compound 12. Extract and compounds will be explored further to develop anticancer drugs.

The isolation and spectroscopic data of a hitherto undescribed polyketide (1) from Hypericum roeperianum Schimp. (Hypericaceae) together with six known compounds (2-7) is herein reported. The structure elucidation is based on extensive 1D- and 2D-NMR, infrared, UV and MS experiments. The structures of the known compounds were confirmed by comparison of their spectroscopic data with those of similar reported compounds in the literature. Some of the isolated compounds had a significant activity against a panel of multidrug-resistant bacterial strains.Supplemental data for this article can be accessed at https://doi.org/10.1080/14786419.2019.1677655.

In the current study forty eight compounds belonging to anthraquinones, naphthoquinones, benzoquinones, flavonoids (chalcones and polymethoxylated flavones) and diterpenoids (clerodanes and kauranes) were explored for their antimicrobial potential against a panel of sensitive and multi-drug resistant Gram-negative and Gram-positive bacteria. The minimal inhibitory concentration (MIC) determinations on the tested bacteria were conducted using modified rapid INT colorimetric assay. To evaluate the role of efflux pumps in the susceptibility of Gram-negative bacteria to the most active compounds, they were tested in the presence of phenylalanine arginine β-naphthylamide (PAβN) (at 30 µg/mL) against selected multidrug resistance (MDR) bacteria. The anthraquinone, emodin, naphthaquinone, plumbagin and the benzoquinone, rapanone were active against methicillin resistant Staphylococcus aureus (MRSA) strains of bacteria with MIC values ranging from 2 to 128 μg/mL. The structure activity relationships of benzoquinones against the MDR Gram-negative phenotype showed antibacterial activities increasing with increase in side chain length. In the chalcone series the presence of a hydroxyl group at C3′ together with a methoxy group and a second hydroxyl group in meta orientation in ring B of the chalcone skeleton appeared to be necessary for minimal activities against MRSA. In most cases, the optimal potential of the active compounds were not attained as they were extruded by bacterial efflux pumps. However, the presence of the PAβN significantly increased the antibacterial activities of emodin against Gram-negative MDR E. coli AG102, 100ATet; K. pneumoniae KP55 and KP63 by >4–64 g/mL. The antibacterial activities were substantially enhanced and were higher than those of the standard drug, chloramphenicol. These data clearly demonstrate that the active compounds, having the necessary pharmacophores for antibacterial activities, including some quinones and chalcones are substrates of bacterial efflux pumps and therefore should be combined to efflux pump inhibitors in the fight against MDR bacterial infections.

Ethnopharmacological relevance: Harungana madagascariensis Lam. ex Poir. (Hypericaceae) is used in folk medicine to treat a variety of human ailments, mainly antibacterial, antifungal, antiviral and viral infections. In the present study, the methanol extract from the leaves (HML) and bark (HMB) of this plant as well as fractions (HMBa-c), sub-fractions (HMBal-5) and compounds isolated from HMBa and HMBb namely betulinic acid (1), madagascin (2), ferruginin A (3) and Kaempferol-3-O-beta-D-glucopyranoside (4) were tested for their antimicrobial activities against a panel of 28 g-negative bacteria including multi drug resistant (MDR) phenotypes.Materials and methods: The broth microdilution method was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the above samples; column chromatography was used for the fractionation and purification of the bark extract whilst the chemical structures of compounds were determined using spectroscopic techniques.Results: Crude extract HMB together with fraction HMBa and sub-fraction HMBa3 were active on the 28 tested bacterial strains. HML as well as fractions HMBb, HMBc and sub-fractions HMBa1, HMBa2, HMBa4 and HMBa5 were selectively active. MIC values below or equal to 1024 mu g/mL were recorded with these samples on 92.9% (for HML and HMBa 4), 82.1% (for HMBb), 78.6% (for HMBa2), 50.0% (for HMBa5) and 42.9% (for HMBc) tested bacteria. For crude material, the lowest MIC value below 8 mu g/mL was obtained with HMB against Escherichia coli ATCC10536 and W3110 strains, and with sub-fraction HMBa3 against Klebsiella pneumoniae K2 strains. MIC values below 10 mu g/mL were recorded with compound 3 against E. coli ATCC10536, Enterobacter aerogenes ATCC13048 and EA294, Pseudomonas aeruginosa PA01, K. pneumoniae K2 and Kp55 and Enterobacter cloacae BM67.Conclusions: Harungana madagascariensis is a potential source of antimicrobial drugs to fight against MDR bacteria. The anthranol 3 is the main antibacterial constituents of the bark of the plant. HMB and compound 3 deserve further investigations to develop natural drug to combat Gram-negative bacteria and otherwise MDR phenotypes. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

A new dihydroflavonol–flavonol biflavonoid derivative, named ericoside was isolated from the ethanol extract of the whole plant of Erica mannii along with the known flavonoid, taxifolin 3-O-α-l-rhamnopyranoside; and two readily available sterols (sitosterol, sitosterol 3-O-β-d-glucopyranoside). The isolation was performed using chromatographic methods and the structure of purified molecules were elucidated using spectroscopic techniques (e.g. MS, NMR) and by comparison with literature data. The crude ethanol extract, ericoside, and taxifolin 3-O-α-l-rhamnopyranoside were tested against ten Gram-negative bacteria including multidrug resistant clinical isolates using a broth microdilution method. The crude ethanol extract showed no noteworthy activity. Of the purified compounds, ericoside displayed moderate activity against the resistant Escherichia coli AG100 with a MIC of 64μg/mL.

Zanthoxylum lemairei is widely used in African folk medicine for its pharmacological relevance. Chemical investigation of the ethanol extract from the leaves of this plant lead to the isolation of two new tetraflavonoids, lemairones A (1) and B (2), along with three known compounds, lupeol, sitosterol, and sitosterol 3-O-β-d-glucopyranoside. The antibacterial screening of the leaves of this plant, characterization of compounds 1 and 2, and their antibacterial activity are reported for the first time. The isolation of the compounds was performed using different chromatographic methods while their structures were elucidated by spectroscopic techniques including MS and NMR, and by comparison of data with those of similar flavonoids reported in the literature. The isolated compounds and the crude extract were tested against ten Gram negative multi-resistance bacterial strains including clinical isolates using a broth dilution method. The crude ethanol extract showed weak activity against the tested bacteria strains with a minimal inhibitory concentration (MIC) ranging from 512 to 1024μg/mL. Among the isolated metabolites, only the new tetraflavonoids were tested. Lemairone A displayed weak activity while lemairone B had moderate activity against the resistant Escherichia coli AG100 with MIC values of 128μg/mL and 64μg/mL respectively. In addition, both molecules displayed weak activity against Klebsiella pneumoniae KP55 (MIC 128μg/mL).