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The efficiency of cancer chemotherapy is seriously hampered by the development of resistance of neoplastic cells to cytotoxic agents. In the present investigation, the cytotoxicity of the dichloromethane-methanol (1:1) extract of Acacia sieberiana (ASL), fractions (ASLa-c) from the leaves and isolated compounds: chrysoeriol-7-O-rutinoside (1), luteolin-7-O-rutinoside (2), chrysoeriol-7-O-β-D-glucopyranoside (3), Apigenin-7-O-β-D-glucopyranoside (4), luteolin-3′,4′-dimethoxylether-7-O-β-D-glucoside (5) and luteolin (6) was investigated. The study was extended to the assessment of the mode of induction of apoptosis by ASL. The resazurin reduction assay (RRA) was used for cytotoxicity studies. Assessments of cell cycle distribution, apoptosis, and reactive oxygen species (ROS) were performed by flow cytometry. A caspase-Glo assay was used to evaluate caspase activities. Botanicals ASL, ASLb and ASLc as well as doxorubicin displayed observable IC50 values towards the nine tested cancer cell lines while ASLa and compounds 1–7 had selective activities. The IC50 values ranged from 13.45 μg/mL (in CCRF-CEM leukemia cells) to 33.20 μg/mL (against MDA-MB-231-BCRP breast adenocarcinoma cells) for ASL, from 16.42 μg/mL (in CCRF-CEM cells) to 29.64 μg/mL (against MDA-MB-231-pcDNA cells) for ASLc, and from 22.94 μg/mL (in MDA-MB-231-BCRP cells) to 40.19 μg/mL (against HCT116 (p53−/−) colon adenocarcinoma cells) for ASLb (Table 1), and from 0.02 μM (against CCRF-CEM cells) to 122.96 μM (against CEM/ADR5000 cells) for doxorubicin. ASL induced apoptosis in CCRF-CEM cells, mediated by ROS production. Acacia sieberiana is a good cytotoxic plant and should be further explored to develop an anticancer phytomedicine to combat both sensitive and drug resistant phenotypes.

Piper capense Linn is a plant used in Cameroon to treat cancer and several other diseases such as urinary tract disorder, fever, stomach-ache and to improve appetite. The methanol extract of Piper capense has been reported for its antiproliferative activity towards several human cancer cell lines. The aim of this work was to evaluate the acute and subchronic oral toxicities of a methanol extract from P. capense fruits on rats. The acute oral toxicity assay was carried out by administration of a single dose of 5000 mg/kg body weight of methanol extract of the Piper capense to five female rats, after which the behavior of the animals and the number of deaths were noted after 48 h. The animals were then kept for observation for 14 days. On the 15th day, the rats were sacrificed and macroscopic observation of the organs was made. Concerning the subchronic toxicity study, the rats composed of males and females received three doses (250, 500 and 1000 mg/kg body weight/day) for a period of 28 days by oral gavage. General animal behavior, food intake, weight gain, organ weights, haematological parameters, serum, and urinary biochemical parameters, and histological sections of liver and kidneys, were evaluated. Methanol extract from the Piper capense fruits did not cause any death in rats that were administered a single dose of 5000 mg/kg body weight of extract and therefore, the letal dose 50 (LD50) of the extract is greater than 5000 mg/kg body weight. Subchronic administration of the methanol extract of Piper capense fruits showed significant variations (P > 0.05) after analysis of certain biochemical parameters: serum urea, urinary urea, alanine aminotransferase (ALAT), aspartate aminotransferase, (ASAT), serum protein; in both male and female rats that received the dose of 1000 mg/kg body weight/day. No major signs of toxicity were observed in the liver and kidneys of animals after analysis of the histological sections performed. Beside, some signs of toxicity were observed, including cell lysis and inflammation on the liver and kidney organs at a dose of 1000 mg/kg body weight/day. Finally, the methanol extract of Piper capense fruits is safe at lower doses, but could cause some damages at doses as high as 1000 mg/kg body weight/day. Consequently, it should be taken with caution when used in therapy.

Background: Pathogenic Escherichia coli is one of the most common causes of acute watery diarrhea among children and adults in the developing world. The severity of infection by this bacterium is a product of many factors, including virulence properties and antimicrobial resistance. This study aimed to determine the distribution of different virulence genes of E. coli isolates in hypertensive and non-hypertensive patients and their association with some selected beta-lactam resistance genes., Methods: At the Douala Laquintinie Hospital, 518 fecal samples were collected from both hypertensive and non-hypertensive patients with enteric infections. E. coli was isolated on eosin-methylene blue agar (EMB) and identified by the Api 20 E Galery. The virulence genes and extended-spectrum β-lactamase-producing (ESBL) E. coli genes were detected by simplex polymerase chain reaction (PCR), while antimicrobial susceptibility was tested by the Kirby-Bauer agar disc diffusion method., Results: The prevalence of enteric infection due to diarrheagenic E. coli (n = 204) was found to be 39.38 % in the general population (n = 518). There were 55 enterovirulent E. coli isolates identified. According to hypertension (HTN), enteropathogenic E. coli (EPEC) isolates were more isolated in hypertensive patients (77.78 %) than in non-hypertensive patients (22.22 %), while enteroaggregative E. coli (EAEC) were the most frequent in non-hypertensive patients (58.33 %). EPEC, EAEC, enterotoxigenic E. coli (ETEC), and Shiga toxin-producing E. coli (STEC) isolates showed higher rates of resistance to amoxicillin (AMO) (90.48 %; 100.00 %; 100.00 %; 100.00 % vs 83.33 %; 85.71 %; 75.00 %; 50.00 %) and SXT (71.43 %; 80.00 %; 75.00 %; 75.00 % vs 0.00 %; 28.57 %; 50.00 %; 25.00 %) in hypertensive patients compared to non-hypertensive patients. The prevalence of ESBL-producing (ESBL-P) E. coli was 87.27 %. The resistance genes bla TEM (64.71 % vs 52.38 %) and bla OXA (23.53 % vs 9.52 %) were more frequently detected in hypertensive patients than in non-hypertensive patients. The high resistance to AMO was correlated with the presence of the bla CTX-M gene (OR: 5.52; 95 % CI: 0.61-49.39; p = 0.093)., Conclusion: This study reveals the high burden of the typical EPEC, EAEC, and ESBL-P E. coli and confirmed the high occurrence of bla CTX-M and bla TEM among ESBL-producing E. coli in hypertensive patients. The study suggests that measures need to be taken to reduce the harmfulness of enterovirulent E. coli and the resistance of enterovirulent E. coli in hypertensive patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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 necroptotic 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) (H 2 DCFH-DA). SCHL and doxorubicin (reference molecule) exhibited cytotoxic effects towards the 18 cancer cell lines tested. The IC 50 values obtained ranged from 3.64 μM (towards CCRF-CEM leukemia cells) to 16.86 μM (against the BRAF-wildtype SKMel-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. MGΔEGFR 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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Phytochemical analysis of the fruits of Raphia vinifera led to the isolation of four new steroidal saponins (1-4), along with six known secondary metabolites (6-10). The structures of the isolated compounds were determined based on the analyses of NMR and mass spectrometric data, and chemical degradation reactions. Among the compounds tested, 1 and 4 showed the most promising cytotoxic activity against the drug-sensitive CCRF-CEM leukemia cell lines, with IC 50 values of 3.55 µM and 7.14 µM, respectively., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This study was aimed to investigate the cytotoxic potential of a natural compound, progenin III on a broad range of cancer cell lines, including various sensitive and drug-resistant phenotypes. The cytotoxicity, progenin III-induced autophagic, ferroptotic and necroptotic cell death were evaluated by the resazurin reduction assay (RRA). Spectrophotometric analysis of caspases activity was performed using caspase-Glo assay. 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) (H 2 DCFH-DA). Progenin III and the reference molecule, doxorubicin exerted cytotoxic effects towards the 18 cancer cell lines tested including animal and human cell lines. The IC 50 values obtained ranged from 1.59 μM (towards CCRF-CEM leukemia cells) to 31.61 μM (against the BRAF-V600E homozygous mutant SKMel-28 melanoma cells) for progenin III. Normal sensitivity was achieved with CEM/ADR5000 cells and HCT116p53 -/- adenocarcinoma cells respectively compared to their sensitive congeners CCRF-CEM cells and HCT116 p53 +/+ cells. Progenin III induced apoptosis in CCRF-CEM cells mediated by caspases 3/7 activation, MMP alteration and increase ROS production, and otherwise autophagy and necroptosis. Progenin III is a potential anticancer molecule that deserves further investigations to develop a novel drug to combat malignant diseases including refractory cancers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Two new furoquinoline alkaloids, maculine B (1) and kokusaginine B (2) and one new dihydrooxazole alkaloid, veprisazole (3), along with four known compounds namely, N 13 -methyl-3-methoxyrutaecarpine (4), flindersiamine (5), skimmianine (6) and tilianin (7) were isolated from the methanol extract of the stem bark of Araliopsis soyauxii Engl. by various chromatographic methods. Their structures were determined using spectrometry and spectroscopic techniques including NMR and MS. The cytotoxicity of the new compounds compared to that of doxorubicin, the reference anticancer compound, was determined on a panel of nine cancer cell lines including sensitive and drug resistant phenotypes. The three previously undescribed alkaloids displayed selective activities. Maculine B (1), the most active one among the newly described compounds, exhibited IC 50 below 30 μM against CCRF-CEM leukemia and U87MG glioblastoma cells., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Chromatographic separation of the extract of the roots of Dorstenia kameruniana (family Moraceae) led to the isolation of three new benzylbenzofuran derivatives, 2-(p-hydroxybenzyl)benzofuran-6-ol (1), 2-(p-hydroxybenzyl)-7-methoxybenzofuran-6-ol (2) and 2-(p-hydroxy)-3-(3-methylbut-2-en-1-yl)benzyl)benzofuran-6-ol(3) (named dorsmerunin A, B and C, respectively), along with the known furanocoumarin, bergapten (4). The twigs of Dorstenia kameruniana also produced compounds 1-4 as well as the known chalcone licoagrochalcone A (5). The structures were elucidated by NMR spectroscopy and mass spectrometry. The isolated compounds displayed cytotoxicity against the sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells, where compounds 4 and 5 had the highest activities (IC 50 values of 7.17 μM and 5.16 μM, respectively) against CCRF-CEM leukemia cells. Compound 5 also showed cytotoxicity against 7 sensitive or drug-resistant solid tumor cell lines (breast carcinoma, colon carcinoma, glioblastoma), with IC 50 below 50 μM, whilst 4 showed selective activity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The aim of this study was to evaluate the antimycobacterial, antigonorrheal and reverse transcriptase activities of five flavonoids: isobachalcone (IBC); kanzanol C (KAN); 4-hydroxylonchocarpin (4-LCP); stipulin (SPL) and amentoflavone (AMF) from Dortenia barteri, together with the crude extract from this plant. The Agar disc diffusion, broth microdilution, microplate alamar blue assay (MABA), radiometric respiratory technique using BACTEC 460 system and the reverse transcriptase (RT) assay were used for the investigations. The results of the antimycobacterial assay showed that the crude extract and compounds were able to prevent the growth of Mycobacteria with MIC<10 microg/ml being recorded with IBC on M. tuberculosis. Results of the killing rate experiment revealed that total inhibition effect on M. tuberculosis H37Rv strain was noted with IBC and SPL at day 9 when tested at 4x MIC. The results of the antigonorrheal assay indicated that MIC values below 10 microg/ml were also recorded with IBC on all the tested N. gonorrhoeae strains, meanwhile good activities (MIC<10 microg/ml) were also noted with the extract, KAN, 4-LCP and SPL on some of these strains. The anti-reverse transcriptase activities of extract and compounds also demonstrated that all samples were able to inhibit at various extents the reverse transcriptase activity, with IBC and 4-LCP showing the best effects. The overall results of this work provided evidence that the crude extract as well as some flavonoids from D. barteri could be potential sources of new antimicrobial drug against tuberculosis (TB), gonorrhea and probably the acquired immunodeficiency syndrome., (Copyright 2010 Elsevier B.V. All rights reserved.)