In vitro antiplasmodial activity-directed investigation and UPLC–MS fingerprint of promising extracts and fractions from Terminalia ivorensis A. Chev. and Terminalia brownii Fresen.

Please read abstract in the article.The Grand Challenges Africa programme is supported by the African Academy of Sciences (AAS), Bill & Melinda Gates Foundation (BMGF), Medicines for Malaria Venture (MMV), and Drug Discovery and Development Centre of University of Cape Town (H3D).https://www.elsevier.com/locate/jethpharm2023-07-09hj2023Chemistr

Ethnobotanical survey of medicinal plants used as insects repellents in six malaria endemic localities of Cameroon

Abstract Background The combined efforts to combat outdoor/indoor transmission of malaria parasites are hampered by the emerging vector resistance in a wide variety of malaria-endemic settings of Africa and the rest of the world, stressing the need for alternative control measures. This study aimed at documenting insect’s repellent plant species used by indigenous populations of 6 localities of East, South, West and Centre regions of Cameroon. Methods Information was gathered through face-to-face interviews guided by a semi-structured questionnaire on the knowledge of medicinal plants with insect repellent properties. Results A total of 182 informants aged from 25 to 75 years were recruited by convenience from May to June 2015. The informants had general knowledge about insects’ repellent plants (78.6%). A total of 16 plant species were recorded as insects’ repellents with 50% being trees. The most cited plants were Canarium schweinfurthii (Burseraceae) (in four localities, 58/182), Elaeis guineensis (Arecaceae) (in three localities, 38/182), Chromolaena odorata (Compositae) (16/182) and Citrus limon (Rutaceae) (11/182) in two localities each. Among the repellent plant species recorded, 50% were reported to be burnt to produce in-house smokes, 31.2% were mashed and applied on the body, and 18.8% were hung in the houses. The leaf was the most commonly used plant part (52.9%), followed by the bark (17.6%). Conclusions This study has shown that rural populations of the 6 targeted localities possess indigenous knowledge on repellent plants that are otherwise cost-effective and better choice for repelling insects including malaria-transmitting mosquitoes. Meanwhile, such practices should be validated experimentally and promoted as sustainable malaria transmission control tools in the remotely located communities

Additional file 1: of Ethnobotanical survey of medicinal plants used as insects repellents in six malaria endemic localities of Cameroon

Ethnobotanical survey of insect/mosquito repellent plants. Interview respondents were identified and further questioned face-to-face using a semi-structured questionnaire. Responses to all questions were recorded following a sequential guideline. (DOC 53 kb

Identification of 3,3'-O-dimethylellagic acid and apigenin as the main antiplasmodial constituents of Endodesmia calophylloides Benth and Hymenostegia afzelii (Oliver.) Harms

Keumoe R, Koffi JG, Dize D, et al. Identification of 3,3'-O-dimethylellagic acid and apigenin as the main antiplasmodial constituents of Endodesmia calophylloides Benth and Hymenostegia afzelii (Oliver.) Harms. BMC complementary medicine and therapies. 2021;21(1): 180.BACKGROUND: Endodesmia calophylloides and Hymenostegia afzelii belong to the Guttiferae and Caesalpiniaceae plant families with known uses in African ethno-medicine to treat malaria and several other diseases. This study aimed at identifying antiplasmodial natural products from selected crude extracts from H. afzelii and E. calophylloides and to assess their cytotoxicity.; METHODS: The extracts from H. afzelii and E. calophylloides were subjected to bioassay-guided fractionation to identify antiplasmodial compounds. The hydroethanol and methanol stem bark crude extracts, fractions and isolated compounds were assessed for antiplasmodial activity against the chloroquine-sensitive 3D7 and multi-drug resistant Dd2 strains of Plasmodium falciparum using the SYBR green I fluorescence-based microdilution assay. Cytotoxicity of active extracts, fractions and compounds was determined on African green monkey normal kidney Vero and murine macrophage Raw 264.7 cell lines using the Resazurin-based viability assay.; RESULTS: The hydroethanolic extract of H. afzelii stem bark (HasbHE) and the methanolic extract of E. calophylloides stem bark (EcsbM) exhibited the highest potency against both Pf3D7 (EC50 values of 3.32±0.15mug/mL and 7.40±0.19mug/mL, respectively) and PfDd2 (EC50 of 3.08±0.21mug/mL and 7.48±0.07mug/mL, respectively) strains. Both extracts showed high selectivity toward Plasmodium parasites (SI>13). The biological activity-guided fractionation led to the identification of five compounds (Compounds 1-5) from HasbHE and one compound (Compound 6) from EcsbM. Of these, Compound 1 corresponding to apigenin (EC50 Pf3D7, of 19.01±0.72muM and EC50 PfDd2 of 16.39±0.52muM), and Compound 6 corresponding to 3,3'-O-dimethylellagic acid (EC50 Pf3D7 of 4.27±0.05muM and EC50 PfDd2 of 1.36±0.47muM) displayed the highest antiplasmodial activities. Interestingly, both compounds exhibited negligible cytotoxicity against both Vero and Raw 264.7 cell lines with selectivity indices greater than 9.; CONCLUSIONS: This study led to the identification of two potent antiplasmodial natural compounds, 3,3'-O-dimethylellagic acid and apigenin that could serve as starting points for further antimalarial drug discovery

Potent antiplasmodial extracts and fractions from Terminalia mantaly and Terminalia superba

Abstract Background The emergence and spread of malaria parasites resistant to artemisinin-based combination therapy stresses the need for novel drugs against malaria. Investigating plants used in traditional medicine to treat malaria remains a credible option for new anti-malarial drug development. This study was aimed at investigating the antiplasmodial activity and selectivity of extracts and fractions from Terminalia mantaly and Terminalia superba (Combretaceae) that are used in Cameroon to treat malaria. Methods Twelve methanolic (m) and water (w) extracts obtained by maceration of powdered dried leaves (l), stem bark (sb) and root (r) of Terminalia mantaly (Tm) and Terminalia superba (Ts) and 12 derived fractions of hexane, chloroform, ethyl acetate and 4 final residues of selected extracts were assessed for antiplasmodial potential in vitro against the chloroquine-resistant PfINDO and the chloroquine-sensitive Pf3D7 strains of Plasmodium falciparum using the SYBR green I-based fluorescence assay. The cytotoxicity of potent extracts and fractions was evaluated in vitro using the MTT assay on HEK239T cell line. Results The antiplasmodial IC50 of extracts from both plants ranged from 0.26 to > 25 µg/mL. Apart from the extracts Tmrm and Tsrw that exerted moderate antiplasmodial activities (IC50: 5–20 µg/mL) and Tmrw that was found to be non-active at the tested concentrations (IC50 > 25 µg/mL), all other tested crude extracts exhibited potent activities with IC50  158) on both resistant PfINDO and sensitive Pf3D7 strains. Four fractions upon further extraction with chloroform and ethyl acetate (TmlwChl, TmsbwChl, TmsbwEA, TsrmEA) afforded from three selected crude extracts (Tmlw, Tmsbw, Tsrm) exhibited highly potent activities against both P. falciparum strains (IC50  109). Conclusions The results achieved in this work validate the reported traditional use of Terminalia mantaly and Terminalia superba to treat malaria. Moreover, the highly potent and selective fractions warrant further investigation to characterize the active antiplasmodial principles and progress them to rodent malaria models studies if activity and selectivity are evidenced

In Vivo Antiplasmodial Activity of Terminalia mantaly Stem Bark Aqueous Extract in Mice Infected by Plasmodium berghei

Background. Terminalia mantaly is used in Cameroon traditional medicine to treat malaria and related symptoms. However, its antiplasmodial efficacy is still to be established. Objectives. The present study is aimed at evaluating the in vitro and in vivo antiplasmodial activity and the oral acute toxicity of the Terminalia mantaly extracts. Materials and Methods. Extracts were prepared from leaves and stem bark of T. mantaly, by maceration in distilled water, methanol, ethanol, dichloromethane (DCM), and hexane. All extracts were initially screened in vitro against the chloroquine-resistant strain W2 of P. falciparum to confirm its in vitro activity, and the most potent one was assessed in malaria mouse model at three concentrations (100, 200, and 400 mg/kg/bw). Biochemical, hematological, and histological parameters were also determined. Results. Overall, 7 extracts showed in vitro antiplasmodial activity with IC50 ranging from 0.809 μg/mL to 5.886 μg/mL. The aqueous extract from the stem bark of T. mantaly (Tmsbw) was the most potent (IC50=0.809 μg/mL) and was further assessed for acute toxicity and efficacy in Plasmodium berghei-infected mice. Tmsbw was safe in mice with a median lethal dose (LD50) higher than 2000 mg/kg of body weight. It also exerted a good antimalarial efficacy in vivo with ED50 of 69.50 mg/kg and had no significant effect on biochemical, hematological, and histological parameters. Conclusion. The results suggest that the stem bark extract of T. mantaly possesses antimalarial activity

Preliminary Structure–Activity Relationship Study of the MMV Pathogen Box Compound MMV675968 (2,4-Diaminoquinazoline) Unveils Novel Inhibitors of Trypanosoma brucei brucei

New drugs are urgently needed for the treatment of human African trypanosomiasis (HAT). In line with our quest for novel inhibitors of trypanosomes, a small library of analogs of the antitrypanosomal hit (MMV675968) available at MMV as solid materials was screened for antitrypanosomal activity. In silico exploration of two potent antitrypanosomal structural analogs (7-MMV1578647 and 10-MMV1578445) as inhibitors of dihydrofolate reductase (DHFR) was achieved, together with elucidation of other antitrypanosomal modes of action. In addition, they were assessed in vitro for tentative inhibition of DHFR in a crude trypanosome extract. Their ADMET properties were also predicted using dedicated software. Overall, the two diaminoquinazoline analogs displayed approximately 40-fold and 60-fold more potency and selectivity in vitro than the parent hit, respectively (MMV1578445 (10): IC50 = 0.045 µM, SI = 1737; MMV1578467 (7): IC50 = 0.06 µM; SI = 412). Analogs 7 and 10 were also strong binders of the DHFR enzyme in silico, in all their accessible protonation states, and interacted with key DHFR ligand recognition residues Val32, Asp54, and Ile160. They also exhibited significant activity against trypanosome protein isolate. MMV1578445 (10) portrayed fast and irreversible trypanosome growth arrest between 4–72 h at IC99. Analogs 7 and 10 induced in vitro ferric iron reduction and DNA fragmentation or apoptosis induction, respectively. The two potent analogs endowed with predicted suitable physicochemical and ADMET properties are good candidates for further deciphering their potential as starting points for new drug development for HAT

Chemical constituents of Mussaenda erythrophylla Schumach. & Thonn. (Rubiaceae) and their chemophenetic significance

Bouzeko ILT, Dongmo FLM, Ndontsa BL, et al. Chemical constituents of Mussaenda erythrophylla Schumach. & Thonn. (Rubiaceae) and their chemophenetic significance. Biochemical Systematics and Ecology. 2021;98: 104329.The chemical investigation of the CH2Cl2/MeOH (1:1) extract from the aerial part of Mussaenda erythrophylla Schumach. & Thonn. (Rubiaceae) resulted in the isolation of sixteen known compounds (1-16) distributed in coumarins, flavonoid glucosides, quinic acid derivatives, triterpenoids, monoglycerid, steroids, tetraterpenoid and polyol. The structures of the compounds were determined by spectrometric and spectroscopic analysis including MS and NMR data followed by their comparison with reported ones in the literature. The chemophenetic significance of the isolated compounds was discussed. The crude extract and some of the isolated compounds were assessed in vitro for their antileishmanial, cytotoxic and antiplasmodial activities. The crude extract of M. erythrophylla showed moderate antileishmanial activity (IC50 = 61.6 mu g/mL) while the hexane soluble fraction showed good antileishmanial activity (IC50 = 31.06 mu g/mL) compared to the reference drug amphotericin B (IC50 = 0.11 mu M). Compounds 11 and 9 also exhibited potent antileishmanial activity (IC50 = 53.7-52.0 mu M). The crude extract as well as the ethyl acetate soluble fraction also exhibited good antiplasmodial activity (IC50 = 7.43 +/- 0.00 mu g/mL and 14.49 +/- 2.96 mu g/mL respectively), while compounds 11, 15 and 16 showed weak activity with IC50 > 20 mu M compared to the reference drug artemisinin (IC50 = 0.014 +/- 0.001 mu M)

High Prevalence of Polyclonal <i>Plasmodium falciparum</i> Infections and Association with Poor IgG Antibody Responses in a Hyper-Endemic Area in Cameroon

Malaria remains a major public health problem worldwide, with eradication efforts thwarted by drug and insecticide resistance and the lack of a broadly effective malaria vaccine. In continuously exposed communities, polyclonal infections are thought to reduce the risk of severe disease and promote the establishment of asymptomatic infections. We sought to investigate the relationship between the complexity of P. falciparum infection and underlying host adaptive immune responses in an area with a high prevalence of asymptomatic parasitaemia in Cameroon. A cross-sectional study of 353 individuals aged 2 to 86 years (median age = 16 years) was conducted in five villages in the Centre Region of Cameroon. Plasmodium falciparum infection was detected by multiplex nested PCR in 316 samples, of which 278 were successfully genotyped. Of these, 60.1% (167/278) were polyclonal infections, the majority (80.2%) of which were from asymptomatic carriers. Host-parasite factors associated with polyclonal infection in the study population included peripheral blood parasite density, participant age and village of residence. The number of parasite clones per infected sample increased significantly with parasite density (r = 0.3912, p p P. falciparum antigens (MSP-1p19, MSP-3 and EBA175) and two soluble antigen extracts (merozoite and mixed stage antigens). Surprisingly, we observed no association between the frequency of polyclonal infection and susceptibility to clinical disease as assessed by the recent occurrence of malarial symptoms or duration since the previous fever episode. Overall, the data indicate that in areas with the high perennial transmission of P. falciparum, parasite polyclonality is dependent on underlying host antibody responses, with the majority of polyclonal infections occurring in persons with low levels of protective anti-plasmodial antibodies