Prostate cancer is a heterogeneous disease, the second deadliest malignancy in men and the most commonly diagnosed cancer among men. Traditional plants have been applied to handle various diseases and to develop new drugs. Medicinal plants are potential sources of natural bioactive compounds that include alkaloids, phenolic compounds, terpenes, and steroids. Many of these naturally-occurring bioactive constituents possess promising chemopreventive properties. In this sense, the aim of the present review is to provide a detailed overview of the role of plant-derived phytochemicals in prostate cancers, including the contribution of plant extracts and its corresponding isolated compounds.

An extensive phytochemical investigation of the EtOH/H₂O (7:3) extracts of Sida rhombifolia L. and Sida acuta Burm. f., yielded a previously undescribed ceramide named rhombifoliamide (1) and a xylitol dimer (2), naturally isolated here for the first time, as well as the thirteen known compounds viz, oleanolic acid (3), β-amyrin glucoside (4), ursolic acid (5), β-sitosterol glucoside (6), tiliroside (7), 1,6-dihydroxyxanthone (8), a mixture of stigmasterol (9) and β-sitosterol (10), cryptolepine (11), 20-Hydroxyecdysone (12), (E)-suberenol (13), thamnosmonin (14) and xanthyletin (15). Their structures were elucidated by the analyses of their spectroscopic and spectrometric data (1 D and 2 D NMR, and HRESI-MS) and by comparison with the previously reported data. The crude extracts, fractions, and some isolated compounds were tested against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum strains. All the tested samples demonstrated moderate and/or significant activities against 3D7 (IC₅₀ values: 0.18―20.11 µg/mL) and Dd2 (IC₅₀ values: 0.74―63.09 µg/mL).

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.

Background: Dacryodes edulis is a plant that belongs to the Burseraceae family. It is widely used traditionally alone or in association with other plants in Cameroonian folk medicine to cure wounds, fever, headaches, and malaria. The aim of this work was to investigate the leaves and stem bark of D. edulis with an emphasis on the antiplasmodial and cytotoxic effects of extracts, fractions, and isolated compounds. Methods: Extracts, fractions, and some isolated compounds were subjected to antiplasmodial activity screening in vitro against chloroquine-sensitive 3D7 and multidrug resistant Dd2 strains of Plasmodium falciparum using a SyBr Green fluorescence-based assay. The cytotoxicity of active extracts, fractions, and compounds was tested against mammalian Raw cell lines using an in vitro resazurin-based viability assay. The structures of the compounds were determined based on their NMR and MS data. The in vivo toxicity using female BALB/c mice was performed on the most active extract according to the protocol of OECD (2002), guideline 423. Results: The hydroethanolic extract from the leaves of D. edulis displayed good antiplasmodial activity with IC₅₀ values of 3.10 and 3.56 μg/mL respectively on sensitive (3D7) and multiresistant (Dd2) strains of P. falciparum. Of the sixteen compounds isolated, 3,3′,4-tri-O-methylellagic acid (4) exhibited the highest antiplasmodial activity against PfDd2 strains with an IC₅₀ value of 0.63 μg/mL. All extracts, fractions, and isolated compounds demonstrated no cytotoxicity against Raw cell lines with CC₅₀ > 250 μg/mL. In addition, the most active extract on both strains of P. falciparum was nontoxic in vivo, with a LD₅₀ greater than 2000 and 5000 mg/kg. A phytochemical investigation of the stem bark and leaves of D. edulis afforded sixteen compounds, including two xanthones (1–2), three ellagic acid derivatives (3–5), one phenolic compound (6), one depside (7), one triglyceride (8), one auranthiamide acetate (9), one gallic acid derivative (10), four triterpenoids (11–14), and two steroids (15–16). Compounds 1, 2, 5, 7, 8, and 9 were herein reported for the first time from the Burseraceae family. Conclusion: This work highlights the good in vitro antiplasmodial potency of the hydroethanolic extract of the leaves of this plant and that of two isolated constituents (3,3′,4-tri-O-methylellagic acid and ethylgallate) from the plant. These biological results support the use of D. edulis in traditional medicine against malaria.

Background.Terminalia mantalyis 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 thein vitroandin vivoantiplasmodial activity and the oral acute toxicity of theTerminalia mantalyextracts.Materials and Methods. Extracts were prepared from leaves and stem bark ofT. mantaly, by maceration in distilled water, methanol, ethanol, dichloromethane (DCM), and hexane. All extracts were initially screenedin vitroagainst the chloroquine-resistant strain W2 ofP. falciparumto confirm itsin vitroactivity, 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 showedin vitroantiplasmodial activity with IC₅₀ranging from 0.809 μg/mL to 5.886 μg/mL. The aqueous extract from the stem bark ofT. mantaly(Tmsb^w) was the most potent (IC50=0.809μg/mL) and was further assessed for acute toxicity and efficacy inPlasmodium berghei-infected mice.Tmsb^wwas safe in mice with a median lethal dose (LD₅₀) higher than 2000 mg/kg of body weight. It also exerted a good antimalarial efficacyin vivowith ED₅₀of 69.50 mg/kg and had no significant effect on biochemical, hematological, and histological parameters.Conclusion. The results suggest that the stem bark extract ofT. mantalypossesses antimalarial activity.