The genus Canthium: A comprehensive summary on its traditional use, phytochemistry, and pharmacological activities.

Canthium Lam. is a genus of flowering plants of the Rubiaceae family with about 80-102 species mainly distributed in Asia, tropical and subtropical Africa. The genus is closely related to Keetia E. Phillips and Psydrax Gaertn. and plants of this genus are used in folk medicine for the treatment of diarrhea, worms, leucorrhoea, constipation, snake bites, diabetes, hypertension, venereal diseases, and malaria. The present review covers a period of 52 years of biological and chemical investigations into the genus Canthium and has resulted in the isolation of about 96 secondary metabolites and several reported biological properties. For the Rubiaceae family, iridoids were reported as being the chemotaxonomic markers of this genus (∼25%). Other reported classes of compounds include alkaloids, flavonoids, phenolic compounds, cyanogenic glycosides, coumarins, sugar alcohols, lignans, triterpenoids, and benzoquinones. The main reported pharmacological properties of most species of this genus include antioxidant, antiplasmodial, antipyretic, anti-inflammatory, antidiabetic, neuroprotective and antimicrobial activities with the latter being the most prominent. Considering the diversity of compounds reported from plants of this genus and their wide range of biological activities, it is considered to be worthy to further investigate them for the discovery of potentially new and cost effective drugs.

4-Benzyloxylonchocarpin and Muracatanes A-C from Ranunculus muricatus L. and Their Biological Effects.

Ranunculus muricatus L. is a spiny fruit buttercup that is used in various traditional medicinal systems. In the current investigation of R. muricatus, the new chalcone 4-benzyloxylonchocarpin (1), the new anthraquinone muracatanes A (2), the new-to-nature anthraquinone muracatanes B (3), and the new naphthalene analog muracatanes C (4) were isolated, in addition to the three previously reported compounds, 4-methoxylonchocarpin (5), ß-sitosterol (6), and ß-sitosterol ß-D-glucopyranoside (7). Their structures were elucidated using 1D (1H and 13C) and 2D (COSY, HSQC, and HMBC) NMR spectroscopy and HR-ESI-MS. Chalcone 1 showed potent acetylcholinesterase inhibitory effects with Ki of 5.39 µM and Ki' of 3.54 µM, but none of the isolated compounds showed inhibitory activity towards butyrylcholinesterase. Anthraquinone 3 illustrated α-glucosidase inhibitory effects with IC50-values of 164.46 ± 83.04 µM. Compound 5 displayed moderate cytotoxic activity towards ovarian carcinoma (A2780, IC50 = 25.4 µM), colorectal adenocarcinoma (HT29, IC50 = 20.2 µM), breast cancer (MCF7, IC50 = 23.7 µM), and thyroid carcinoma (SW1736, IC50 = 26.2 µM) while it was inactive towards pharynx carcinoma (FaDu: IC50 > 30 µM).

Cichorins D-F: Three New Compounds from Cichorium intybus and Their Biological Effects.

Cichorium intybus L., (chicory) is employed in various traditional medicines to treat a wide range of diseases and disorders. In the current investigation, two new naphthalane derivatives viz., cichorins D (1) and E (2), along with one new anthraquinone cichorin F (3), were isolated from Cichorium intybus. In addition, three previously reported compounds viz., ß-sitosterol (4), ß-sitosterol ß-glucopyranoside (5), and stigmasterol (6) were also isolated from Cichorium intybus. Their structures were established via extensive spectroscopic data, including 1D (1H and 13C) and 2D NMR (COSY, HSQC and HMBC), and ESIMS. Cichorin E (2) has a weak cytotoxic effect on breast cancer cells (MDA-MB-468: IC50: 85.9 µM) and Ewing's sarcoma cells (SK-N-MC: IC50: 71.1 µM); cichorin F (3) also illustrated weak cytotoxic effects on breast cancer cells (MDA-MB-468: IC50: 41.0 µM and MDA-MB-231: IC50: 45.6 µM), and SK-N-MC cells (IC50: 71.9 µM). Moreover compounds 1-3 did not show any promising anthelmintic effects.

Therapeutic potential of glycyrrhetinic acids: a patent review (2010-2017).

INTRODUCTION: Glycyrrhetinic acids (GAs) viz., 18ß-glycyrrhetinic acid and 18α-glycyrrhetinic acid, are oleanane-type triterpenes having a carboxylic acid group at C-30, and are extracted from the Chines herbal medicine licorice (Glycyrrhiza uralensis). Although the pharmacological properties of GAs have long been known, attention to them has greatly increased in recent times due to their cytotoxic activity. AREAS COVERED: This review represents the patents granted about natural and synthetic glycyrrhetinic acid analogs from January 2010 to December 2017, the advances made by research groups in conjunction with pharmaceutical companies in the discovery of new natural or synthetic glycyrrhetinic acid analogs. EXPERT OPINION: GAs demonstrate excellent cytotoxic, antimicrobial, enzyme inhibitory, antiinflammatory, antioxidant, analgesic, and antiviral effects. It is interesting to note that the C-3(OH) and C30-CO2H functional groups make GAs very attractive lead structures for medicinal scientists since these functionalities allow the generation of further chemical diversity for improved pharmacological effects. Moreover, various GA analogues have been prepared via modification of the C30-CO2H. It is noteworthy that the C-30 amide of GA demonstrated better cytotoxic effects compared to the parent compounds. In addition, GAs have the capability to conjugate with other anticancer drugs or be converted into their halo or amino analogs which is expected to stimulate medicinal chemist to synthesize new lead compounds in cancer drug discovery.

Sarniensine, a mesembrine-type alkaloid isolated from Nerine sarniensis, an indigenous South African Amaryllidaceae, with larvicidal and adulticidal activities against Aedes aegypti.

A new mesembrine-type alkaloid, named sarniensine, was isolated together with tazettine, lycorine, the main alkaloid, and 3-epimacronine from Nerine sarniensis, with the last two produced for the first time by this plant. This Amaryllidaceae, which is indigenous of South Africa, was investigated for its alkaloid content, because the organic extract of its bulbs showed strong larvicidal activity with an LC50 value of 0.008µgµL-1 against first instar Aedes aegypti larvae and with an LD50 value 4.6µg/mosquito against adult female Ae. aegypti, which is the major vector for dengue, yellow fever and the Zika virus. The extract did not show repellency at MED value of 0.375mgcm2 against adult Ae. aegypti. Sarniensine was characterized using spectroscopic and chiroptical methods as (3aR,4Z,6S,7aS)-6-methoxy-3a-(2'-methoxymethyl-benzo [1,3]dioxol-1'-yl)-1-methyl-2,3,3a,6,7,7a-hexahydro-1H-indole. It was less effective against larva at the lowest concentration of 0.1µgµL-1, however it showed strong adulticidal activity with an LD50 value of 1.38±0.056µgmosquito-1.

A Novel Biflavonoid from Rhus leptodictya.

An investigation of the leaves of Rhus leptodictya led to the isolation of the new biflavonoid: 5,5",6",7,8-pentahydroxy-2,2"-bis(p-hydroxyphenyl)-4H,4"H- 3,7"-bichromene-4,4"-dione the structure of which was established by NMR spectroscopy and mass spectrometry.

Phytochemical and Antimicrobial Screening of Flavanones and Chalcones from Galenia africana and Dicerothamnus rhinocerotis.

This study focused on an 80% ethanol:water extract of Galenia africana and Dicerothamnus rhinocerotis in which a phytochemical study revealed the presence of flavonoids as the major secondary plant metabolites. Eleven pure flavonoids viz., (E)-2',4'-dihydroxychalcone 1, (S)-7-hydroxyflavanone 2, (E)-2',4'-dihydroxy-2,3-dihydrochalcone 3, (S)-5,7-dihydroxyflavanone 4, (S)-2',5,7,-trihydroxyflavanone 5, (S)-5,7-dihydroxy-2'-methoxyflavanone 6, 5,7-dihydroxy-4H-chromen-4-one 7, (S)-5-hydroxy-7-methoxyflavanone 8 and (E)-2-hydroxy-3',6'-dimethoxychalcone 9 were isolated from G. africana, while [sakuranetin] (S)-4',5-dihydroxy-7-methoxyflavanone 10 and [eriodictyol-3',7-dimethyl ether] (S)-4',5-dihydroxy-3',7-dimethoxyflavanone 11 were isolated from D. rhinocerotis. Compounds 6 and 9 are new while this is the first reported isolation of 1, 2, 3, 4, 5, 7, 8, 10 and 11 from these plants. All isolated compounds were tested for their antimycobacterial activity against the reference strain Mtb H37Rv. The most active compound, 9, demonstrated a MIC99 of 5 µM against Mtb H37Rv American Type Culture (ATCC) and (ATCC27294), which were also sensitive to Isoniazid (INH) and Rifampicin. The antibacterial activity of 9 might be ascribed to the presence of features such as the α,ß-unsaturated ketone and the substitution patterns on the A and B rings.

Nizwaside: a new anticancer pregnane glycoside from the sap of Desmidorchis flava.

The sap from the succulent Desmidorchis flava (N.E.Br) Meve and Liede yielded a new pregnane glycoside, named nizwaside whose structure was established using 1D and 2D NMR techniques as well as mass spectrometry (ESIMS). Nizwaside was tested for anticancer, DPPH antioxidant, urease enzyme inhibition, α-glucosidase enzyme inhibition and acetylcholinesterase inhibition activities. Interestingly, nizwaside showed significant anti-proliferative effects on MDA MB231 breast cancer cells with an IC(50) of 23.5 µg/ml. Moreover, nizwaside was more effective than Doxorubicin, a well-known clinical anticancer drug, in suppressing MDA MB231 cell proliferation even at concentrations lower than that of Doxorubicin (75 µg/ml nizwaside vs. 100 µg/ml Doxorubicin). On the other hand, nizwaside showed relatively weak antioxidant activity with 15 % inhibition.

The genus Pluchea: phytochemistry, traditional uses, and biological activities.

In this review, literature data on phytochemical and biological investigations on the genus Pluchea are compiled. Pluchea is a genus of flowering plants in the Asteraceae family and comprises ca. 80 species distributed mainly in Northern and Southern America, Africa, Asia, and Australia. Sesquiterpenoids and flavonoids are the main constituents of this genus. Compounds isolated from plants of the Pluchea genus display a variety of biological properties, viz., anticancer, antileishmanial, immunosuppressive, antioxidant, anti-acetylcholinesterase, antimicrobial, trypanocidal, hepatoprotective, cytotoxic, larvicidal, anti-ulcer, anti-inflammatory, and antinociceptive activities.

Kenganthranol F, a new anthranol from Psorospermum aurantiacum.

A new anthranol, kenganthranol F, was isolated from the ethyl acetate extracts of the seeds and the whole plant of the Cameroonian plant Psorospermum aurantiacum (Hypericaceae), together with fifteen known compounds viz., ferruginin B, vismin, vismion D, haronginanthrone, kenganthraquinone, kenganthranol B and kenganthranol E isolated from the fruits and 3-geranyloxyemodinanthrone, 2-geranylemodin, bianthrone A1, vismione D, 1,8-dihydroxy-3-geranyloxy-6-methylanthraquinone, vismione M, vismiaquinone, vismiaquinone C being isolated from the whole plant. The structure of the new isomer of kenganthranol F was determined to be 1,8,10-trihydroxy-3,4-[2,2-dimethyldihydropyrano]-6-methyl-2,5-bis-(3,3-dimethylallyl)-anthrone.

Chemistry and biology of genus Vismia.

CONTEXT: Many herbal remedies have been employed in the treatment and management of various human ailments since the beginning of human civilization. Vismia is an extensive genus of the family Hypericaceae and consists of small trees inhabiting the tropical and subtropical regions of South and Central America. Within the framework of an International Cooperative Biodiversity Groups project, three Vismia species were studied for their potential anticancer activity. OBJECTIVES: This review is an extensive study of the available scientific literature published and comprises of the ethnopharmacological, phytochemical and therapeutic potential of genus of plants under the umbrella Vismia. METHODS: The present review includes 134 natural products with 47 references compiled from the major databases, viz., Chemical Abstracts, Science Direct, SciFinder, PubMed, Dr. Dukes Phytochemical and Ethnobotany, CIMER, and InteliHealth. RESULTS: An exhaustive survey of the accessed literature revealed that flavonoids, flavanols, xanthones, anthraones, anthraquinones, benzophenones, lignans, steroids, monoterpenes and triterpenes constituted the major classes of phytoconstituents of this genus. Pharmacological reports revealed that it is used for skin diseases such as dermatitis, leprosy, syphilis, herpes, scabies and eczemas, and as an anticancer for human breast, CNS, and lung cancer cell lines. CONCLUSION: Genus Vismia plants seem to hold great potential for an in-depth investigation towards discovering biological activities, especially for the treatment of cancers affecting our society. Through this review, the authors hope to attract the attention of natural product researchers throughout the world to focus on the unexplored potential of Vismia plants, with the view of developing new formulations with an improved therapeutic value.

Chemistry and biology of the genus Voacanga.

CONTEXT: Herbal remedies have been employed for the treatment and management of various ailments since the beginning of human civilization. Voacanga is an extensive genus of the family Apocynaceae and consists of small trees inhabiting the tropical and subtropical regions of Africa. Voacanga plants have been used in the treatment of leprosy, diarrhea, and generalized edema, convulsions in children as well as to treat cases of orchitis, ectopic testes and gonorrhea. OBJECTIVES: The aim of this review is to present as much information as was established from the available scientific literature. The present review comprises the ethnopharmacological, phytochemical and therapeutic potential of the plant genus Voacanga. METHODS: The present review reports on 111 natural products as found in 44 references compiled from the major databases, viz., Chemical Abstracts, Science Direct, SciFinder, PubMed, Dr. Dukes Phytochemical and Ethnobotany, CIMER, and InteliHealth. RESULTS: An exhaustive survey of the literature revealed that indole alkaoids and steroids constitute the major classes of phytoconstituents of this genus. Pharmacological reports revealed that products derived from this genus have been used for the treatment of cancer, and for CNS, cardiotonic, antituberculosis, acetylcholinesterase (AChE), butyrylcholinesterase, antagonistic, anti-diarrheal activities.

Multifunctional cytotoxic agents from Anacardium occidentale.

The effects of anacardic acids and cardols isolated from the cashew nut and apple Anacardium occidentale (Anacardiaceae) on murine B16-F10 melanoma cells were tested. Although anacardic acids and cardols were found to inhibit tyrosinase, a key enzyme in melanin synthesis, melanogenesis in melanocytes was not suppressed in cultured cells but rather enhanced. Both anacardic acids and cardols exhibited moderate cytotoxicity.

Minor secondary metabolic products from the stem bark of Plumeria rubra Linn. displaying antimicrobial activities.

Four new iridoids viz., plumeridoids A, B, and C and epiplumeridoid C were isolated from the stem bark of Plumeria rubra Linn. together with twenty-four known compounds viz., 1-( P-hydroxyphenyl)propan-1-one, isoplumericin, plumericin, dihydroplumericin, allamcin, fulvoplumerin, allamandin, plumieride, P- E-coumaric acid, 2,6-dimethoxy- P-benzoquinone, scopoletin, cycloart-25-en-3 beta,24-diol, 2,4,6-trimethoxyaniline, ajunolic acid, ursolic acid, oleanolic acid, beta-amyrin acetate, betulinic acid, lupeol and its acetate, 2,3-dihydroxypropyl octacosanoate, glucoside of beta-sitosterol, and a mixture of common sterols (stigmasterol and beta-sitosterol). Their structures were determined by means of spectroscopic data including HREIMS, 1H NMR, 13C NMR, 2D NMR (HMQC, HMBC, NOESY) and by comparison with published data. All but one of thirteen tested compounds exhibited antifungal, antialgal, and/or antibacterial activities.

Evaluation of lipoxygenase inhibitory activity of anacardic acids.

6-Alkylsalicylic acids inhibit the linoleic acid peroxidation catalyzed by soybean lipoxygenase-1 (EC 1.13.11.12, type 1) competitively and without pro-oxidant effects. This activity is largely dependent on the nature of their alkyl side chains. Inhibitory activities of anacardic acids, viz. 6-pentadec(en)ylsalicylic acids, isolated from the cashew Anacardium occidentale, were initially used for comparison because their aromatic head portions are the same. Consequently, the data should be interpreted to mean that changes in the hydrophobic side chain tail portions of the molecules evaluated correlate with the specific activity determined.

Antimicrobial prenylated dihydrochalcones from Eriosema glomerata.

Two new natural dihydrochalcones exhibiting antimicrobial properties together with six known compounds were isolated from the Cameroonian medicinal plant Eriosema glomerata. The structures of the new dihydrochalcones were elucidated as 2',4'-dihydroxy-4-methoxy-3'-( gamma, gamma-dimethylallyl)dihydrochalcone and 2',4'-dihydroxy-3'-( gamma, gamma-dimethylallyl)dihydrochalcone by detailed spectroscopic analysis. The two new dihydrochalcones, named erioschalcones A ( 1) and B ( 2), demonstrated significant inhibitory activity against the microbial strains Bacillus megaterium, Escherichia coli, Chlorella fusca and Microbotryum violaceum.

Design and evaluation of anacardic acid derivatives as anticavity agents.

On the basis of antibacterial anacardic acids, 6-pentadecenylsalicylic acids, isolated from the cashew apple, Anacardium occidentale L. (Anacardiaceae), a series of 6-alk(en)ylsalicylic acids were synthesized and tested for their antibacterial activity against Streptococcus mutans ATCC 25175. Among them, 6-(4',8'-dimethylnonyl)salicylic acid was found to exhibit the most potent antibacterial activity against this cariogenic bacterium with the minimum inhibition concentration (MIC) of 0.78 microg/ml.

Inhibition of soybean and potato lipoxygenases by bhilawanols from bhilawan (Semecarpus anacardium) nut shell liquid and some synthetic salicylic acid analogues.

Bhilawanol diene (3) isolated from bhilawan nut shell liquid was found to be a potent inhibitor of both soybean and potato lipoxygenases with IC50 values of 0.85 microM and 1.1 microM, respectively. However, the monoene (2) and saturated (1) bhilawanols exhibited relatively lower inhibitory activity. In addition, inhibition studies with synthetic analogues of salicylic acid (4-8) suggested that the unsaturated lipophilic side chain may be an absolute requirement for inhibitory activity.