Unusually cyclized triterpenoids: occurrence, biosynthesis and chemical synthesis.

Covering: 2009 to 2021Biosynthetically, most of the syntheses of triterpenes follow the cascade cyclization and rearrangement of the acyclic precursors viz., squalene (S) and 2,3-oxidosqualene (OS), which lead to the very well known tetra- and pentacyclic triterpene skeletons. Aside from these, numerous other triterpenoid molecules are also reported from various natural sources and their structures are derived from "S" and "OS" via some unusual cyclization operations which are different from the usual tetra- and pentacyclic frameworks. Numerous compelling advances have been made and reported in the identification of these unusual cyclized mono-, di-, tri- and tetracyclic triterpenes between 2009 and 2021. Besides a dramatic increase in the newly isolated uncommon cyclized triterpenoids, substantial progress in the (bio)-synthesis of these triterpenes has been published along with significant progress in their biological effects. In this review, 180 new unusual cyclized triterpenoids together with their demonstrated biogenetic pathways, syntheses and biological effects will be categorized and discussed.

Knowledge, Attitudes and Perceptions towards COVID-19 Vaccinations: A Cross-Sectional Survey in Pakistan.

Background and Objectives: Several vaccines have been approved for the prevention of the coronavirus disease, discovered on 31 December in Wuhan, China. Pakistan procured vaccines from various countries. However, the lack of knowledge and reluctance of the general population to embrace the use of the vaccines are considered to be the major determinant of the slow vaccination rate. Hence, it is necessary to evaluate the willingness of the general population about their perception of the COVID-19 vaccination. Materials and Methods: A cross sectional survey based on a self-structured questionnaire comprising 18 questions was conducted (from 21 April-21 June) on 400 Pakistani participants to evaluate their knowledge, attitude, and perception towards the COVID-19 vaccination. Chi-square independent t-test and one-way Anova including a multiple step wise linear regression were used to draw conclusions about the results. p < 0.05 was considered significant. Results: A total of 400 participants responded in the knowledge, attitude, and perception (KAP) survey of which 46.5% were female and 53.5% were male. The mean age of participants was 36.08 years. This survey showed a poor knowledge (50.5%), a fair attitude (75.1%) and a poor perception (58.1%) towards the COVID-19 vaccination. Higher mean knowledge and attitude scores were reported in the age group 21-40, females, and unmarried urban citizens. Regression analysis showed that age, education, residence, and employment status influenced the knowledge and perception score to a considerable extent. Conclusions: The findings reflect an inadequate knowledge and perception on the one hand, but a better attitude towards the COVID-19 vaccination. This knowledge attitude and perception (KAP) survey will help in better understanding the opinion of the general population towards vaccination, and will be useful for policy makers and health care authorities aiming to increase the vaccination rate.

Fruit Peels: Food Waste as a Valuable Source of Bioactive Natural Products for Drug Discovery.

Fruits along with vegetables are crucial for a balanced diet. These not only have delicious flavors but are also reported to decrease the risk of contracting various chronic diseases. Fruit by-products are produced in huge quantity during industrial processing and constitute a serious issue because they may pose a harmful risk to the environment. The proposal of employing fruit by-products, particularly fruit peels, has gradually attained popularity because scientists found that in many instances peels displayed better biological and pharmacological applications than other sections of the fruit. The aim of this review is to highlight the importance of fruit peel extracts and natural products obtained in food industries along with their other potential biological applications.

Deciphering the chemical instability of sphaeropsidin A under physiological conditions - degradation studies and structural elucidation of the major metabolite.

The fungal metabolite sphaeropsidin A (SphA) has been recognised for its promising cytotoxicity, particularly towards apoptosis- and multidrug-resistant cancers. Owing to its intriguing activity, the development of SphA as a potential anticancer agent has been pursued. However, this endeavour is compromised since SphA exhibits poor physicochemical stability under physiological conditions. Herein, SphA's instability in biological media was explored utilizing LC-MS. Notably, the degradation tendency was found to be markedly enhanced in the presence of amino acids in the cell medium utilized. Furthermore, the study investigated the presence of degradation adducts, including the identification, isolation and structural elucidation of a major degradation metabolite, (4R)-4,4',4'-trimethyl-3'-oxo-4-vinyl-4',5',6',7'-tetrahydro-3'H-spiro[cyclohexane-1,1'-isobenzofuran]-2-ene-2-carboxylic acid. Considering the reduced cytotoxic potency of aged SphA solutions, as well as that of the isolated degradation metabolite, the reported antiproliferative activity has been attributed primarily to the parent compound (SphA) and not its degradation species. The fact that SphA continues to exhibit remarkable bioactivity, despite being susceptible to degradation, motivates future research efforts to address the challenges associated with this instability impediment.

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.

Synthesis and in vitro growth inhibitory activity of novel silyl- and trityl-modified nucleosides.

Seventeen silyl- and trityl-modified (5'-O- and 3',5'-di-O-) nucleosides were synthesized with the aim of investigating the in vitro antiproliferative activities of these nucleoside derivatives. A subset of the compounds was evaluated at a fixed concentration of 100µM against a small panel of tumor cell lines (HL-60, K-562, Jurkat, Caco-2 and HT-29). The entire set was also tested at varying concentrations against two human glioma lines (U373 and Hs683) to obtain GI50 values, with the best results being values of ∼25µM.

Anti-proliferative and computational studies of two new pregnane glycosides from Desmidorchis flava.

Two new pregnane glycosides named desmiflavasides C (1) and D (2) were isolated from the sap of Desmidorchis flava (N.E.Br.) Meve & Liede and have had their structures confirmed from 1D and 2D NMR spectroscopic techniques and mass spectrometry (ESIMS). Further, the effects of desmiflavasides C (1) and D (2) on the proliferation of breast and ovarian cancer cells as well as normal breast epithelial cells in culture were examined. Interestingly, desmiflavasides C (1) and D (2) were able to cause a substantial decline in the viability of cancer cells in a concentration-dependent manner. Moreover, treatment of normal cells with compound 2 resulted in no significant growth inhibition, indicating that its cytotoxicity was selective towards cancer cells. Furthermore, the activity of compound 2 against cancer as well as normal epithelial cells was found to be similar to that of a previously reported pregnane glycoside, nizwaside (3). Molecular docking studies of desmiflavasides C (1) and D (2) and nizwaside (3) were carried out to ascertain if it was possible to predict any important binding orientations required of small molecule drug candidates with suggested protein target molecules for the purposes of being able to predict the affinity and activity to an acceptable degree by such compounds. Desmiflavaside D (2) showed a relatively good binding affinity (-22.4449kcal/mol) as compared to the other two compounds viz., nizwaside (3) (-20.0319kcal/mol), and desmiflavaside C (1) (-19.4042kcal/mol). Docking results of the three pregnane glycosides viz., 1-3 revealed that these ligand molecules can accurately interact with the target protein.

Alkaloids with Activity against the Zika Virus Vector Aedes aegypti (L.)-Crinsarnine and Sarniensinol, Two New Crinine and Mesembrine Type Alkaloids Isolated from the South African Plant Nerine sarniensis.

Two new Amaryllidaceae alkaloids, belonging to the mesembrine- and crinine-types, named crinsarnine (1) and sarniensinol (2), were isolated from the dried bulbs of Nerine sarniensis together with bowdensine (3), sarniensine (4), hippadine (5) and 1-O-acetyl-lycorine (6). Crinsarnine (1) and sarniensinol (2) were characterized using spectroscopic and chiroptical methods as (1S,2S,4aR,10bS)-2,7-dimethoxy-1,2,3,4,4a,6-hexahydro-5,11b-ethano[1,3]dioxolo-[4,5-j]phenanthridin-1-yl acetate and (6-(3aR,4Z,6S,7aS)-6-methoxy-1-methyl-2,3,3a,6,7,7a-hexa-hydro-1H-indol-3a-yl)benzo[d][1,3]dioxol-5-yl)methanol, respectively. Furthermore, the complete spectroscopic characterization of bowdensine (3) is reported for the first time. Compounds 1-6 were evaluated against the Orlando reference strain of Aedes aegypti. None of compounds showed mortality against 1st instar Ae. aegypti larvae at the concentrations tested. In adult topical bioassays, only 1 displayed adulticidal activity with an LD50 = 2.29 ± 0.049 µg/mosquito. As regards the structure-activity relationship, the pretazettine and crinine scaffold in 2 and 4 and in 1 and 3 respectively, proved to be important for their activity, while the pyrrole[de]phenanthridine scaffold present in 5 and 6 was important for their reactivity. Among the pretazettine group compounds, opening of the B ring or the presence of a B ring lactone as well as the trans-stereochemistry of the A/B ring junction, appears to be important for activity, while in crinine-type alkaloids, the substituent at C-2 seems to play a role in their activity.

Microsphaerol and seimatorone: two new compounds isolated from the endophytic fungi, Microsphaeropsis sp. and Seimatosporium sp.

A new polychlorinated triphenyl diether named microsphaerol (1), has been isolated from the endophtic fungus Microsphaeropsis sp. An intensive phytochemical investigation of the endophytic fungus Seimatosporium sp., led to the isolation of a new naphthalene derivative named seimatorone (2) and eight known compounds, i.e., 1-(2,6-dihydroxyphenyl)-3-hydroxybutan-1-one (3), 1-(2,6-dihydroxyphenyl)butan-1-one (4), 1-(2-hydroxy-6-methoxyphenyl)butan-1-one (5), 5-hydroxy-2-methyl-4H-chromen-4-one (6), 2,3-dihydro-5-hydroxy-2-methyl-4H-chromen-4-one (7), 8-methoxynaphthalen-1-ol (8), nodulisporins A and B (9 and 10, resp.), and daldinol (11). The structures of 1 and 2 were elucidated by detailed spectroscopic analysis including (1) H- and (13) C-NMR, COSY, HMQC, HMBC, and HR-EI-MS, while the structures of the known compounds were deduced from comparison of their spectral data with those in the literature. Preliminary studies revealed that microsphaerol (1) showed good antibacterial activities against B. Megaterium and E. coli, and good antilagal and antifungal activities against C. fusca, M. violaceum, respectively. On the other hand, seimatorone (2) exhibited moderate antibacterial, antialgal, and antifungal activities.

Seimisochromenes A and B: two new dihydroisochromenes from the endophytic fungus, Seimatosporium sp.

Two new dihydroisochromenes, named seimisochromenes A and B (1 and 2), were isolated from an endophytic fungus, Seimatosporium sp. The structures of seimisochromenes A and B have been determined from 1D ((1)H and (13)C NMR spectra) and 2D (COSY, HMQC, HMBC, and NOESY) NMR experiments.

C1,C2-ether derivatives of the Amaryllidaceae alkaloid lycorine: retention of activity of highly lipophilic analogues against cancer cells.

As a continuation of the studies aimed at the development of new anticancer agents derived from the Amaryllidaceae alkaloid lycorine, 35 C1,C2-ether analogues of this natural product were synthesized. The compounds were evaluated for antiproliferative activities in vitro in a panel of tumor cell lines with varied levels of apoptosis resistance. A strong correlation between the compound lipophilicity and anticancer activity was observed, indicating that cell permeability properties must be an important determinant in the design of lycorine-based anticancer agents. A theoretical docking model, consistent with the experimental observations, is presented.

Coniothyren: a new phenoxyphenyl ether from the endophytic fungus, Coniothyrium sp.

Phytochemical investigation of the endophytic fungus Coniothyrium sp. resulted in the isolation of a new phenoxyphenyl ether, named coniothyren (1), and two known compounds, coniol (2) and (+)-epoxydon (3). The structure of the new compound was elucidated by detailed spectroscopic analysis, namely, (1)H NMR, (13)C NMR, COSY, HMQC, HMBC, and HR-EI-MS. Preliminary studies demonstrated that (+)-epoxydon (3) displayed good antibacterial and antialgal activities toward Bacillus megaterium and Chlorella fusca, respectively.

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.

Advances in the total synthesis of biologically important callipeltosides: a review.

An overview of synthetic efforts toward callipeltosides A-C, macrolide natural products, from 1998 to present is provided. The emphasis of this review is the various ring-constructing and stereoforming strategies employed in these synthetic routes.

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.

Marine life as a source for breast cancer treatment: A comprehensive review.

Breast cancer, one of the most significant tumors among all cancer cells, still has deficiencies for effective treatment. Moreover, substitute treatments employing natural products as bioactive metabolites has been seriously considered. The source of bioactive metabolites are not only the most numerous but also represent the richest source. A unique source is from the oceans or marine species which demonstrated intriguing chemical and biological diversity which represents an astonishing reserve for discovering novel anticancer drugs. Notably, marine sponges produce the largest amount of diverse bioactive peptides, alkaloids, terpenoids, polyketides along with many secondary metabolites whose potential is mostly therapeutic. In this review, our main focus is on the marine derived secondary metabolites which demonstrated cytotoxic effects towards numerous breast cancer cells and have been isolated from the marine sources such as marine sponges, cyanobacteria, fungi, algae, tunicates, actinomycetes, ascidians, and other sources of marine organisms.

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.

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.