30-norfriedelanes and other compounds from the stem bark and fruits of Caloncoba glauca (Achariaceae), their antiplasmodial activity, structure-activity relationship and computational validation.

Two new 30-norfriedelane triterpenoids namely glaucalactone C (1) and glaucanoic acid (2) along with sixteen known compounds (3-18) have been isolated from the methanolic extracts of the stem bark and fruits of Caloncoba glauca (P.Beauv.) Gilg (Achariaceae). The structures of all the isolated compounds have been established with the aid of their extensive spectroscopic analyses (1D and 2D-NMR) as well as mass spectrometry. Six compounds (1-5, 9) were screened for antiplasmodial activity against two strains P. falciparum Dd2 and P. falciparum 3D7. The results showed that glaucanoic acid (2) was the most active one with IC50 values of (3.5 ± 0.1 µg/mL) and (4.6 ± 0.7 µg/mL) against PfDd2 and Pf3D7, respectively, while glaucalactone C (1) moderately inhibited PfDd2 (9.4 ± 0.1 µg/mL) and weakly Pf3D7 (15.9 ± 2.3 µg/mL). The molecular docking analyses of the isolated compounds showed that compounds 1-4 and 9-11 are potential drug targets and were further supported by their ADMET studies that revealed welwitschiilactones B and C (4 and 5) as well as ß-sitosterol (10) as the most qualified compounds to be safe as drugs. The results indicate that C. glauca is an important source of good candidates in new antiplasmodial drug development.

Bioassay-Guided Isolation of Antiplasmodial Compounds from Hypericum lanceolatum Lam. (Hypericaceae) and Their Cytotoxicity and Molecular Docking.

In Cameroon, malaria is still the cause of several deaths yearly and leading to the continued search for new potent leads to fight against Plasmodium falciparum. Medicinal plants like Hypericum lanceolatum Lam. are introduced in local preparations for the treatment of affected people. The bioassay-guided fractionation of the crude extract of the twigs and stem bark of H. lanceolatum Lam. led to the identification of the dichloromethane-soluble fraction as the most active (with 32.6% of the parasite P. falciparum 3D7 survival) which was further purified by successive column chromatography to obtain four compounds identified by their spectrometric data as two xanthones 1,6-dihydroxyxanthone (1) and norathyriol (2) and two triterpenes betulinic acid (3) and ursolic acid (4). In the antiplasmodial assay against P. falciparum 3D7, the triterpenoids 3 and 4 displayed the most significant potencies with IC50 values of 2.8 ± 0.8 µg/mL and 11.8 ± 3.2 µg/mL, respectively. Furthermore, both compounds were also the most cytotoxic against P388 cell lines with IC50 values of 6.8 ± 2.2 µg/mL and 2.5 ± 0.6 µg/mL, respectively. Further insights on the inhibition method of the bioactive compounds and their drug-likeness were obtained from their molecular docking and ADMET studies. The results obtained help in identifying additional antiplasmodial agents from H. lanceolatum and support its use in folk medicine for the treatment of malaria. The plant might be considered as a promising source of new antiplasmodial candidates in new drug discovery.

One new constituent from the stem bark of Chrysophyllum lacourtianum De Wild. (sapotaceae).

The phytochemical investigation of the methanol extract of the stem bark of Chrysophyllum lacourtianum led to the isolation and characterization of one new secondary metabolite, lacourtianal (1), together with eight known compounds. Compounds 2; 3; 5; 6; 7 and 9 were reported for the first time from Chrysophyllum genus. The structures of compounds 1-9 were elucidated on the basis of 1 D and 2 D NMR spectroscopic and mass spectrometric data as well as comparison with the literature. The antibacterial activity of the methanol extract, fractions and compounds 1-9 were evaluated against bacterial strains. The methanol extract exhibited moderate activity against Staphylococcus aureus NR4674 with MIC values of 500 µg/mL. The n-hexane fraction showed moderate activity against Staphylococcus aureus (ATCC 43300 and ATCC 25923) with MIC values of 125 µg/mL and ursolic acid (5) exhibited strong activity against Enterobacter aerogenes CPC and Escherichia coli ATCC 25322 with MIC values of 7.8 and 3.9 µg/mL respectively.

Naturally occurring dimeric triterpenoids: Occurrence, chemistry and bioactivities.

The triterpenes represent one of the most reported subclasses of specialized metabolites from the plant kingdom. They play a key role in the protection of plants and their metabolism in addition to displaying a high structural diversity and large scale of biological activities. The scaffold can undergo several reactions like oxidation or substitution at different positions of the skeleton leading to the formation of several types of compounds. More specifically, triterpene dimer is a small group of compounds found in nature (from plants precisely). Until 2021, the chemical and pharmacological works reported in the literature indicated the identification of 90 natural dimeric triterpenes and 11 synthetic derivatives from 19 plants species and very few of them have been biologically evaluated for their antibacterial, antioxidant, antiproliferative or molluscicide activities. This review aims to compile the literature on the occurrence, chemistry and biological activities of the triterpenoid dimers. To attend this goal, a literature survey has been done in a number of online libraries including Scifinder, PubMed, Web of Science and Google Scholar using keywords terpene, triterpene, dimer, celastroloid without language restriction. This paper provides the easiest access to the information on triterpene dimers for readers and researchers in view to enhancing the continuity of research works on this topic.

Contribution of Meliaceous plants in furnishing lead compounds for antiplasmodial and insecticidal drug development.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria remains one of the greatest threats to human life especially in the tropical and sub-tropical regions where it claims hundreds of thousands of lives of young children every year. Meliaceae represent a large family of trees and shrubs, which are widely used in African traditional medicine for the treatment of several ailments including fever due to malaria. The in vitro and in vivo antiplasmodial as well as insecticidal investigations of their extracts or isolated compounds have led to promising results but to the best of our knowledge, no specific review on the traditional uses, phytochemistry of the antiplasmodial, insecticidal and cytotoxic lead compounds and extracts of Meliaceae plants has been compiled. AIMS: To review the literature up to 2021 on the Meliaceae family with antiplasmodial, insecticidal and cytotoxic activity. MATERIALS AND METHODS: A number of online libraries including PubMed, Scifinder, Google Scholar and Web of Science were used in searching for information on antiplasmodial metabolites from Meliaceous plants. The keywords Meliaceae, malaria, Plasmodium, Anopheles and antiplasmodial were used to monitor and refine our search without language restriction. RESULTS: The phytochemical investigations of genera of the family Meliaceae led to the isolation and characterization of a wide range of structural diversity of compounds, 124 of which have been evaluated for their antiplasmodial potency against 11 chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum strains. A total of 45 compounds were reported with promising insecticidal potentials against two efficient vector species, Anopheles stephensi Liston and A. gambiae Giles. Limonoids were the most abundant (51.6%) reported compounds and they exhibited the most promising antiplasmodial activity such as gedunin (3) which demonstrated an activity equal to quinine or azadirachtin (1) displaying promising larvicidal, pupicidal and adulticidal effects on different larval instars of A. stephensi with almost 100% larval mortality at 1 ppm concentration. CONCLUSION: Studies performed so far on Meliaceae plants have reported compounds with significant antiplasmodial and insecticidal activity, lending support to the use of species of this family in folk medicine, for the treatment of malaria. Moreover, results qualified several of these species as important sources of compounds for the development of eco-friendly pesticides to control mosquito vectors. However, more in vitro, in vivo and full ADMET studies are still required to provide additional data that could guide in developing novel drugs and insecticides.

Three phragmalin-type limonoids orthoesters and the structure of odoratone isolated from the bark of Entandrophragma candollei (Meliaceae).

The phytochemical exploration of the Entandrophragma candollei stem bark extract led to the isolation and identification of twenty compounds including three undescribed phragmalin-class limonoids named encandollens C-E (1-3), the undescribed protolimonoid 5 together with sixteen known compounds. The structures of all the isolated compounds were determined by interpretation of their spectroscopic and spectrometric data including HRMS, 1D and 2D NMR analyses. The assignment of the absolute and relative stereochemistry of the undescribed compounds was achieved using SC-XRD analyses as well as NOESY experiments. The previously reported structure of odoratone (5a) was corrected as 23 R,24 S-dihydroxy-22 S,25-epoxytirucall-7-en-3-one (5) based on its NMR and SC-XRD data. Prieurianin (4) exhibited high cytotoxic activity on KB3-1 cell lines with an IC50 of 1.47 µM compared to the reference griseofulvin (IC50 = 17-21 µM). The results of the in silico docking of compound 4 supported and delivered further insights on its cytotoxicity.

Bioguided chemical study of Boswellia dalzielii Hutch. (Burseraceae) for antibacterial agents and a new glucopyranoxylmethoxybenzyle.

Stem barks of Boswellia dalzielii are used traditionally for the treatment of various bacterial infections. A bioassay guided fractionation of the MeOH-CH2Cl2 (1/1, v/v) stem barks extract led to the isolation of fourteen compounds 1-14, identified based on spectroscopic data. Dalzienoside (1) is reported here for the first time. The broth microdilution method was used to evaluate the antibacterial activity of the crude extract, fractions and compounds against six bacterial strains. The crude extract exhibited moderate antibacterial activity with MIC of 250 µL/ml; two fractions showed significant activities with MICs ranging from 7.8 to 125 µg/ml, while α-boswellic acid (2), ß-boswellic acid (3), acetyl-11-keto-ß-boswellic acid (4) from these fractions exhibited strong activities with MIC value of 3.125 µg/mL against Staphylococcus aureus, Salmonella typhi, Enterobacter cloacae, Streptococcus pneumonia and Pseudomonia aeruginosa. This study gives insight into the antibacterial constituents of the stem bark of B. dalzielii and justifies its use in ethnomedicine.

Ergostane-type steroids from the Cameroonian 'white tiama' Entandrophragma angolense.

Two new ergostane-type steroids named tiamenones A and B (1-2) were isolated from the bark of Entandrophragma angolense (Meliaceae) along with ten known compounds identified as 20S-hydroxy-4,6,24(28)-ergostatrien-3-one (3), 3ß,7α,20ß-trihydroxyergosta-5,24(28)-diene (4), 3ß,5α-dihydroxyergosta-7,22-diene (5), stigmasterol, ß-sitosterol, ß-amyrin, oleanolic acid, asperphenamate, sucrose and daucosterol. The structures of the isolated compounds have been established using NMR spectroscopic and mass spectrometric analyses. The assignment of relative and absolute configurations of compound 1 was achieved by a NOESY experiment and comparison of its NMR data with those of known compound reported in literature. Compounds 1-3, ß-amyrin and asperphenamate were evaluated for their antibacterial potencies against five bacterial model strains viz. Escherichia coli DSMZ 1058, Pseudomonas agarici DSMZ 11810, Bacillus subtilis DSMZ 704, Micrococcus luteus DMSZ 1605 and Staphylococcus warneri DSMZ 20036 and their cytotoxicity on two cell lines KB3-1 and HT-29. No potencies were exhibited by the tested compounds even at the highest concentration of 0.5 mg/mL. Compounds 1-3 were found to be potential HIV-1 inhibitors based on their molecular docking analyses.

seco-Tiaminic acids B and C: Identification of two novel 3,4-seco-tirucallane triterpenoids isolated from the root of Entandrophragma congoënse (Meliaceae).

Chemical investigation of the roots of Entandrophragma congoënse (Meliaceae) led to the isolation of two new 3,4-seco-tirucallane triterpenes, namely seco-tiaminic acids B and C (1 and 2) together with nine known compounds: 3,4-secotirucalla-21-formyl-23-oxo-4(28),7,24-trien-3-oic acid (3), methyl angolensate (4), molucensin N (5), molucensin O (6), piscidinol A (7), 7α,20(S)-dihydroxy-4,24(28)-ergostadien-3-one (8), 24-methylene-cholest-5-en-3ß,7α-diol (9), entilin A (10), and entilin B (11). Their structures were determined using extensive spectroscopic methods including 1D and 2D NMR, HRMS, and CD analyses; new results were compared to existing data in the literature. The two newly identified seco-tiaminic acids showed moderate antiplasmodial and cytotoxic activities against a chloroquine-sensitive strain of the malaria parasite (Plasmodium falciparum NF54) and were cytotoxic toward an L6 rat skeletal myoblast cell line, respectively.

Antiplasmodial and Cytotoxic Triterpenoids from the Bark of the Cameroonian Medicinal Plant Entandrophragma congoënse.

Eight new triterpenoids, prototiamins A-G (1-6, 9) and seco-tiaminic acid A (10), were isolated along with four known compounds from the bark of Entandrophragma congoënse. Their structures were elucidated by means of HRMS and different NMR techniques and chemical transformations. Assignments of relative and absolute configurations for the new compounds were achieved using NOESY experiments and by chemical modification including the advanced Mosher's method. Additionally, the structure and relative configuration of compound 3 were confirmed by single-crystal X-ray diffraction analysis. Compounds 1, 3, and 5 displayed significant in vitro antiplasmodial activity against the erythrocytic stages of chloroquine-sensitive Plasmodium falciparum strain NF54. Prototiamin C (3) was the most potent of the compounds isolated, with an IC50 value of 0.44 µM. All compounds tested showed low cytotoxicity for the L6 rat skeletal myoblast cell line.

Minor secondary metabolites from the bark of Entandrophragma congoënse (Meliaceae).

Two new tirucallane-type triterpenoids were isolated from the bark of Entandrophragma congoënse (Meliaceae) along with five known compounds gladoral A, bipendensin, 4-hydroxymethyl-3,5-dimethyldihydrofuran-2(3H)-one, scopoletin and 5,7-dimethoxy-6-hydroxycoumarin. Their structures were elucidated by means of spectroscopic analyses including 1D and 2D-NMR spectroscopy, high resolution mass spectrometric data as well as the comparison of data with those reported in the literature. The tested compounds (1-4) displayed moderated antiplasmodial activity against erythrocytic stages of chloroquine-resistant Plasmodium falciparum strain NF54 and low cytotoxicity on L6 cell lines. All the isolated compounds are reported for the first time from the genus Entandrophragma.