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Two hitherto unknown neo -clerodane-type diterpenoids along with twelve known compounds have been isolated from Conyza pyrrhopappa Sch.Bip. ex A.Rich, a medicinal plant traditionally used across tropical Africa to relieve fever. The structures of isolates have been elucidated by a combination of spectroscopic techniques. The crude extract and the isolated compounds were evaluated in the Hela-S3 cell line and in a panel of microorganisms (bacteria and fungi) at concentrations up to 50 µg/mL. The new compounds were inactive while the pentamethylated flavonoids showed low to significant activity against the cancer cell line used. However, none of the samples showed any activity against the tested microorganisms at this concentration. The present manuscript is the first investigation of the cytotoxicity of phytochemicals and extract from C. pyrrhopappa .

Ethnopharmacological Relevance: Infections due to multidrug-resistant (MDR) bacteria constitute a real problem in the public health worldwide. Hypericum roeperianum Schimp. ex A. Rich (Hypericaceae) is used traditionally for treatment of various ailments such as abdominal pains, constipation, diarrhea, indigestion, nausea, and bacterial diseases., Aim of the Study: This study was aimed at investigating the antibacterial and antibiotic-modifying activity of the crude methanol extracts (HRB), ethyl-acetate soluble fraction (HRBa), residual material (HRBb), and 11 compounds from the bark of Hypericum roeperianum against multi-drug resistant (MDR) bacteria expressing active efflux pumps., Materials and Methods: The antibacterial activity, the efflux pump effect using the efflux pump inhibitor (EPI), phenylalanine-arginine-ß-naphthylamide (PAβN), as well as the antibiotic-modifying activity of samples were determined using the broth micro-dilution method. Spectrophotometric methods were used to evaluate the effects of HRB and 8,8-bis(dihydroconiferyl) diferulate (11) on bacterial growth, and bacterial membrane damage, whereas follow-up of the acidification of the bacterial culture was used to study their effects on bacteria proton-ATPase pumps., Results: The crude extract (HRB), HRBa, and HRBb had selective antibacterial activity with MICs ranging from 16 to 512 μg/mL. Phytochemical 11 displayed the best antibacterial activity (0.5 ≤ MIC ≤ 2 μg/mL). The activity of HRB and 11 in the presence of EPI significantly increased on the tested bacteria strains (up to 32-fold). The activity of cloxacillin (CLO), doxycycline (DOX), and tetracycline (TET), was considerably improved (up to 64-fold) towards the multidrug-resistant Enterobacter aerogenes EA-CM64 strain. The crude extract (HRB) and 11 induced the leakage of bacterial intracellular components and inhibited the proton-ATPase pumps., Conclusions: The crude extract (HRB) and 8,8-bis(dihydroconiferyl)diferulate from the bark of Hypericum roeperianum are good antibacterial candidates that deserve further investigations to achieve antibacterial drugs to fight infections involving MDR bacteria., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A total of nine sesquiterpenoid lactones together with phenolic compounds and other terpenes were identified from the crude methanol extract of Elephantopus mollis Kunth. Compounds were isolated using different chromatographic techniques and their structures were determined by NMR and IR spectroscopy as well as mass spectrometry. The structures of some detected compounds were assigned based on LC-ToF-ESI-MS screening of main fractions/subfractions from flash chromatography and comparison with isolated analogues as standards. The findings revealed not only the in-source loss of water as the base peak in hirsutinolides but also the in-source loss of corresponding alcohol when the oxygen at position 1 is alkylated. The present study also draws up a complement of data with respect to hirsutinolide-like sesquiterpene lactones whose LC-MS characteristics are not available in the literature. The chemophenetic significance is also discussed. Some of the isolated compounds were reported for the first time to be found in the species, the genus as well as the plant family. The medium-polar fractions of the crude extract, also containing the larger amount of sesquiterpenoid lactones, exhibited activity both against a cancer cell line and bacterial strains. Isolated lactones were also active against the cancer cell line, while the chlorogenic derivatives also valuable in Elephantopus genus showed potent radical scavenging activity. This is the first report of cytotoxic and antibacterial activities of our samples against the tested strains and cell line. The present study follows the ongoing research project dealing with the characterization of taxa with antibacterial and antiparasitic activities from Cameroonian pharmacopeia.

Bacterial multidrug resistance causes many therapeutic failures, making it more difficult to fight against bacterial diseases. This study aimed to investigate the antibacterial activity of extract, fractions, and phytochemicals from Plectranthus glandulosus (Lamiaceae) against multidrug-resistant (MDR) Gram-negative phenotypes expressing efflux pumps. The crude extract after extraction was subjected to column chromatography, and the structures of the isolated compounds were determined using spectrometric and spectroscopic techniques. Antibacterial assays of samples alone and in the presence of an efflux pump inhibitor (phenylalanine-arginine β -naphthylamide, PA β N) were carried out using the broth microdilution method. The phytochemical study of P. glandulosus plant extract afforded seven major fractions (A-G) which lead to the isolation of seventeen known compounds. The ethanol extract of P. glandulosus was not active at up to 1024  μ g/mL, whereas its fractions showed MICs varying from 32 to 512  μ g/mL on the studied bacteria. Fraction C of P. glandulosus showed the lowest MIC (32  μ g/mL) on E. coli ATCC8739 strain. Fraction D presented the highest activity spectrum by inhibiting the growth of 90% (9/10) of the studied bacteria. The presence of PA β N has improved the activity of extract and all fractions. Overall, the tested phytochemicals showed low activity against the studied bacteria. The overall results obtained in this study show that some fractions from P. glandulosus , mainly fractions C and D, should be investigated more for their possible use to fight against MDR bacteria., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Gravalain Nanmeni et al.)

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; H 2 DCFH-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), sitosterol (7) and stigmasterol (8), β-sitosterol 3-O-β- 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 IC 50 values ranged from 6.1 μg/mL (against CCRF-CEM cells) to 44.2 μg/mL (against BRAF-V600E homozygous mutant melanoma cells) for PSCb; from 4.3 μM (against CCRF-CEM cells) to 21.8 μM (against HCT116 p53 -/- ) for compound 2 and from 0.02 μM (against CCRF-CEM cells) to 123.0 μM (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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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: The proliferation and resistance of microorganisms area serious threat against humankind and the search for new therapeutics is needed. The present report describes the antiplasmodial and anticancer activities of samples isolated from the methanol extract of Albizia zygia (Mimosaseae)., Material: The plant extract was prepared by maceration in methanol. Standard chromatographic, HPLC and spectroscopic methods were used to isolate and identify six compounds (1-6). The acetylated derivatives (7-10) were prepared by modifying 2-O-β-D-glucopyranosyl-4-hydroxyphenylacetic acid and quercetin 3-O-α-L-rhamnopyranoside, previously isolated from A. zygia (Mimosaceae). A two-fold serial micro-dilution method was used to determine the IC 50s against five tumor cell lines and Plasmodium falciparum., Results: In general, compounds showed moderate activity against the human pancreatic carcinoma cell line MiaPaca-2 (10 < IC 50 < 20 μM) and weak activity against other tumor cell lines such as lung (A-549), hepatocarcinoma (HepG2) and human breast adenocarcinoma (MCF-7and A2058) (IC 50 > 20 μM). Additionally, the two semi-synthetic derivatives of quercetin 3-O-α-L-rhamnopyranoside exhibited significant activity against P. falciparum with IC 50 of 7.47 ± 0.25 μM for compound 9 and 6.77 ± 0.25 μM for compound 10, higher than that of their natural precursor (IC 50 25.1 ± 0.25 μM)., Conclusion: The results of this study clearly suggest that, the appropriate introduction of acetyl groups into some flavonoids could lead to more useful derivatives for the development of an antiplasmodial agent.

Background: Successful cancer chemotherapy is hampered by resistance of cancer cells to established anticancer drugs. Numerous natural products reveal cytotoxicity towards tumor cells., Purpose: The present study was aimed to determine the cytotoxicity of a betaine-type alkaloid, ungeremine, towards 9 cancer cell lines including various sensitive and drug-resistant phenotypes. The mode of action of this compound was further investigated., Methods: The cytotoxicity, ferroptotic and necroptotic cell death were determined by the resazurin reduction assay. Caspase activation was evaluated using the caspase-Glo assay. Flow cytometry was applied for the analysis of cell cycle analysis (PI staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP) (JC-1) and reactive oxygen species (ROS) (H 2 DCFH-DA). Apoptotic, necroptotic and autophagic markers were determined by Western blotting. CCRF-CEM leukemia cells were used for all mechanistic studies., Results: Ungeremine displayed cytotoxic activity towards the 9 cancer cell lines tested, including drug-sensitive and MDR phenotypes. The IC 50 values obtained varied from 3.67 µM (in MDA-MB-231-BCRP breast carcinoma cells) to 75.24 µM (against in CEM/ADR5000 leukemia cells) for ungeremine and from 0.02 µM (against CCRF-CEM cells) to 122.96 µM (against CEM/ADR5000 cells) for doxorubicin (control drug). Ungeremine induced ferroptosis, necroptosis, autophagy as well as apoptosis mediated by caspase activation, MMP alteration and increase ROS production., Conclusion: The present investigation showed that ungeremine is a promising cytotoxic compoundthat could be further explored in the future to develop new anticancer drugs to fight sensitive and resistant phenotypes., (Copyright © 2019 Elsevier GmbH. All rights reserved.)