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African Trypanosomiasis caused by trypanosome parasites continues to be a major neglected health problem, particularly in developing countries. Current treatments are marked by serious side effects, low effectiveness, high toxicity, and drug resistance prompting the need to develop novel, safe, effective, and alternative antitrypanosomal compounds. Anopyxis klaineana is an ethnomedicinal plant used in West Africa to treat many ailments including protozoan diseases. In this study, we investigated the antitrypanosomal potential of stem bark extracts of A. klaineana through in vitro and in silico approaches. A. klaineana extracts were tested for their antitrypanosomal activities against Trypanosoma brucei parasite in vitro using Alamar blue assay. In addition, the antioxidant and cytotoxic activities were determined. LC-ESI-QTOF-MS was used to identify potential bioactive compounds present in the A. klaineana extracts. Bioactive compounds identified were subjected to molecular docking studies against Trypanosoma brucei's trypanothione reductase (TR) and Uridine Diphosphate Galactose 4′-Epimerase (UDP). The A. klaineana extracts (methanol, hexane, chloroform, and ethyl acetate) exhibited potential anti-trypanosomal activities with IC50 values of 21.25 ± 0.755,4.35 ± 0.166,2.57 ± 0.153 and 22.92 ± 2.321 μg/mL respectively. Moreover, the methanolic crude extracts showed moderate cytotoxicity against HepG2 and PNT2 cells, with IC50 values of 68.0 ± 2.05 and 78.7 ± 2.63 μg/mL respectively. LC-MS analysis revealed the presence of 24 bioactive compounds with 5 being druglike. Risperidone, Ranolazine, Dihydro-7-Desacetyldeoxygedunin, 6 beta-Hydroxytriamcinolone acetonide, and Dimethylmatairesinol were identified as novel potential inhibitors of TR and UDP with binding affinities of −10.4, −7.9, −8.7, −8.4 and −7.1 kcal/mol respectively against TR and −10.8, −8.4, −8.4, −7.6 and −8.1 respectively against UDP. This study indicates that A. klaineana has potential antitrypanosomal properties and therefore may have the potential to be developed as a therapeutic intervention for treating African trypanosomiasis.

Malaria continues to be a major public health concern, particularly for children and pregnant women in areas where the disease is endemic. Developing safe and efficient antimalarial therapies to fight the disease is essential. Medicinal plants represent a potential source for the development of new antimalarial drugs. Tetrapleura tetraptera is a plant native to West Africa and traditionally used to treat several diseases including Malaria. Here, we investigated the antiplasmodial activities of T. tetraptera fruit extracts against the chloroquine-sensitive (Pf3D7) and chloroquine-resistant (PfDD2) strains of Plasmodium falciparum in vitro using SYBR green assay. In addition, the antioxidant potential of the fruit extracts was also determined. LC-MS analysis was carried out to identify the bioactive compounds in the extracts. Molecular docking studies provide significant prima facie evidence of inhibition hence, to evaluate the potential inhibition of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH), a validated malaria drug target, the identified compounds were docked against PfDHODH. Strong antiplasmodial activities were demonstrated by the ethyl acetate and ethanolic extracts of T. tetraptera fruit, with IC50 values of 16.12 ± 0.04 µg/mL and 2.06 ± 0.02 µg/mL against the Pf3D7 strain, respectively. In the DPPH radical scavenging experiment, the ethanolic extract revealed considerable antioxidant activity with an EC50 value of 0.21 ± 0.82 mg/mL. Seven bioactive compounds were identified in the extract using LC-MS analysis. N-Methyl-1H-indole-3-propanamide (I), Tazolol (II), and Isopentyl salicylate (III) were identified as potential inhibitors of PfDHODH with high binding affinities ranging from -32.08 to -30.69 kcal/mol. The potential lead compounds also interacted with Gly181, Leu531, and Arg265, which are critical amino acid residues in the catalytic activity of PfDHODH. These findings support the traditional use of T. tetraptera fruit extracts for the treatment of malaria and as promising avenues for antimalarial drug development.

Background: Malaria remains a major health concern in developing countries with high morbidity and mortality, especially in pregnant women and infants. A major obstacle to the treatment of malaria is a low effectiveness and an increase resistance of the parasite to antimalarial drugs. As a result, there is an ongoing demand for new and potent antimalarial drugs. Medicinal plants remain a potential source for the development of new antimalarial drugs. Amongst them is Dissotis rotundifolia is an ethnomedical important plant used in West Africa to treat malaria. Purpose: This study aimed at identifying new potential antifolates by virtually screening phytochemicals characterized from the whole plant methanolic extract of D. rotundifolia against Plasmodium falciparum Dihydrofolate Reductase (PfDHFR). Methods: LC-ESI-Q-TOF-MS analysis was employed to identify the phytochemicals present in the whole plant methanolic extract of D. rotundifolia. These phytochemicals were docked against the catalytic site of PfDHFR. The docking protocol was evaluated using the Area Under the Curve (AUC) of a Receiver Operating Characteristic (ROC) curve. The binding mechanisms and the drug-likeness of the phytochemicals were characterized. A 100 ns Molecular Dynamics (MD) simulation and Molecular Mechanics-Poisson Boltzmann Surface Area (MM-PBSA) calculations were utilized to analyze the stability, the energy decomposition per residue and the binding free energy of the potential leads. Results: Twenty nine phytochemicals were characterized and docked against PfDHFR. Dimethylmatairesinol, flavodic acid, sakuranetin, and sesartemin were identified as potential leads with binding affinities of -8.4, -8.9, -8.6, and -8.9 kcal/mol respectively, greater than a stringent threshold of -8.0 kcal/mol. The potential leads also interacted hydrophobically with critical residue Phe58. A novel critical residue, Leu46 was identified to be crucial in the catalytic activity of PfDHFR. The potential leads were also predicted to be anti-protozoal with a probability of active (Pa) value ranging from 0.319 to 0.537. Conclusion: This study elucidates the potential inhibition of PfDHFR by dimethylmatairesinol, flavodic acid, sakuranetin and sesartemin present in D. rotundifolia. These compounds are druglike, do not violate Lipinski's rule of five, have a high binding affinity to PfDHFR, and interact with crucial residues involved in the catalytic activity PfDHFR. Dimethylmatairesinol, flavodic acid, sakuranetin and sesartemin could therefore be further investigated and developed as new antifolate drugs for malaria.

Plasmodium species, which are spread by female Anopheles mosquitoes, are responsible for malaria. Out of the five major Plasmodium species, Plasmodium falciparum and Plasmodium vivax are the most deadly and invasive species responsible for 99.7% and 75% of malaria cases in Africa and America respectively. Despite the invasive nature of malaria, the Plasmodium parasite continues to develop resistance to current drugs. It is therefore imperative to come up with new therapeutics to combat malaria. Previous studies have reported that Limonoids from the Meliaceae family possess antimalarial properties. This study therefore aims at employing computational approaches to identify potential antimalarial Limonoids by targeting PvFKBP35. PvFKBP35 has been reported to be a suitable target for antimalarial therapeutics as it is involved in various physiological activities including transcription, protein stability and folding. Molecular docking, Molecular Dynamics simulation and Molecular Mechanics-Poisson Boltzmann Surface Area calculation were employed to identify the potential leads. Sixteen [16] Limonoids extracted from the bark of the stem of Entadrophragma angolense were virtually screened against PvFKPB35. The top hit compounds were subjected to 500 ns Molecular Dynamics simulation and Molecular Mechanics – Poisson Boltzmann Surface Area calculations to examine their stability and free binding energy. Two potential leads, compounds 1 and 11 with binding energies −6.3 and −5.4 kcal/mol respectively were identified. The potential leads in complexed with PvFKBP35 had an average root mean square deviation of 1.18 ± 0.19 Å and 3.12 ± 0.60 Å, indicating their stability. Solvent Accessible Surface Area was utilized to predict the penetrative ability of the compounds into the binding pocket. Average Solvent Accessible Surface Area values of 327.88 ± 47.54 A2, 402.18 ± 39.81 A2 were obtained for compounds 1 and 11 respectively. ADMET estimations of compounds 1 and 11 predicted them to be druglike and do not violate Lipinski's rule of five. Compounds 1 and 11 need be tested in vitro to validate their antimalarial activity although they were predicted to be antiprotozoal with Pa values 0.207 and 0.162. These compounds can then serve as the scaffold for the design of novel antimalarial therapeutics.

Spotted fever group rickettsiae are tickborne, obligatory intracellular, gram-negative bacteria with a worldwide distribution. However, the distribution of each species of spotted fever group rickettsiae is limited to geographic areas [...]