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Rosemary (Rosmarinus officinalis L.), a culinary herb of the family Lamiaceae, has promising anticancer activity. This overview has updated the current knowledge on the chemistry and anticancer properties of rosemary extract, carnosic acid, carnosol, and rosmanol, focusing on colon and prostate cancer cells since they are the most susceptible. The information was procured from Google, Google Scholar, PubMed, PubMed Central, Science Direct, J-Stage, and PubChem. Phenolic compounds isolated from the aerial parts of R. officinalis are flavonoids, phenolic acids, diterpenes, triterpenes, terpenoids, and phenylpropanoids. Some of the compounds are new to science, to the genus, and to the species. Almost 30 compounds possess anticancer properties. Rosemary extracts contain abietane diterpenes, with carnosic acid, carnosol, and rosmanol being the most common. Their molecular structures are similar to three fused aromatic rings. Carnosic acid has a –COOH group at C20, carnosol has a lactone ring occurs across the B ring, and rosmanol has a –OH group at C7. Against colon and prostate cancer cells, the rosemary extract and diterpenes inhibited cell viability and induced apoptosis and G2/M phase cell cycle arrest. The inhibition of cell migration and adhesion has also been reported. The rosemary extract and diterpenes also inhibited colon and prostate cancer xenograft in mice. Rosemary extract is more cytotoxic than the diterpenes due to its polyphenols such as flavonoids and triterpenes. In vitro and in vivo cytotoxic activities involve different molecular targets and signalling pathways. Some prospects and areas for future research are suggested.

A new abietane-type diterpenoid, rubesanolidic acid (1), alongside six known compounds including β-sitosterol (2), lupeol (3), betulinic acid (4) ursolic acid (5), β-sitosterol 3-O-β-D-glucopyranoside (6) and stigmasterol 3-O-β-D-glucopyranoside (7) were isolated from the roots of Burkea africana through column chromatography. Their structures were elucidated from spectroscopic analyses (UV, IR, MS, 1D and 2D NMR) data and by comparison with data from previous studies. The extract and compounds were tested for their α-amylase inhibition. The extract was more active than the isolated compounds with a percentage inhibition of 51.0 ± 2.5% at 400 µg/mL and was the only sample showing above 50% inhibition at this dose. Amongst the isolated compounds and at the dose of 400 µg/mL, the new diterpenoid Rubesanolidic acid exibited the highest percentage inhibition of α-amylase of 38.2 ± 2.0% while β-sitosterol showed the lowest inhibition of 9.6 ± 0.5%. The results indicate that B. africana is a potential source of antidiabetic compounds.

A new icetexane diterpenoid, 11, 12, 20α-trihydroxyl-7β-methoxyicetexa-8, 11, 13-triene-19, 10-lactone [Phyllane A (1)], and a new abietane diterpenoid, 7β, 20-epoxy-3β, 17-acetoxy-abieta-8, 11, 13...

The name Salvia, the largest genus of Lamiaceae, derives from the Latin "salvere" (= to feel good, healthy). In the Mediterranean basin, S. officinalis has been used since the time of the ancient Egyptians for medicinal purposes. Pliny the Elder was the first known author to describe a plant called "Salvia" by the Romans. Recent scientific research has confirmed the antituberculosis properties of numerous species present in the traditional ethnobotany.

Prunella vulgaris is a widely used edible Chinese medicinal plant. In the present study, two new abietane-type diterpenoids, abietoquinones A (1) and B (2), were isolated from this plant by an immunosuppressive bioassay-guided isolation procedure. Their structures were elucidated unambiguously by NMR spectroscopic analysis, single-crystal X-ray crystallography, and electronic circular dichroism calculations. Compounds 1 and 2 bear a cyclohex-2-ene-1,4-dione moiety, which is uncommon among abietane diterpenes. Also, abietoquinone A (1) suppressed murine splenocyte proliferation and decreased the production of proinflammatory cytokines induced by concanavalin A (Con A) in vitro. In Con A-challenged mice, preinjection with 1 significantly ameliorated liver injury. Additionally, abietoquinone A (1) exhibited inhibitory activities against the proliferation of murine splenocytes and human T cells induced by anti-CD3/anti-CD28 monoclonal antibodies (mAbs).

Twenty-four diterpenoids (1-24), classified into nine diverse carbon skeletal types, 8-nor-7(8→14),9(8→7)-di-abeo-abietane (1, 2, and 13), 7(8→14),9(8→7)-di-abeo-abietane (3 and 4), 6-nor-6,7-seco-abietane (5 and 6), 6,7-seco-abietane (7 and 11), 9,10-seco-abietane (8), abietane (9, 10, and 14-21), 11(9→8),20(10→11)-di-abeo-abietane (12), 15(13→12)-abeo-abietane (22 and 23), and 4,5-seco-20(10→5)-abeo-abietane (24), respectively, were isolated from the roots of Salvia deserta. The structures of 10 new diterpenoids, named salviadesertins A-J (1-10), were elucidated by spectroscopic data interpretation, quantum-chemical calculations including calculated 13C NMR-DP4+ analysis and electronic circular dichroism as well as X-ray crystallography analysis. The absolute configurations of compounds 1-3, 7, 14, and 22 were defined by single-crystal X-ray diffraction analysis. All the isolated diterpenoids 1-24 were evaluated for their cytotoxicity against five cancer cell lines, and 6-hydroxysalvinolone (14) showed micromolar potencies against MCF-7, A-549, SMMC-7721, and HL-60 cells, whereas the other diterpenoids were inactive (half-maximal inhibitory concentration greater than 10.0 μM).

Phytochemical investigation of the aqueous methanol and butanol extracts of Salvia multicaulis from Jordan resulted in the isolation of 17 compounds including one new abietane diterpene derivative that was identified as 2,20-dihydroxyferruginol. Structural elucidation of all isolated compounds was based on extensive analysis of their spectroscopic data.

The phytochemical profile of Lepechinia meyenii (Walp.) Epling and Lepechina floribunda (Benth.) Epling obtained by liquid chromatography associated with high-resolution mass spectrometry is presented. Forty eight compounds were detected exhibiting a variety of salvianolic acids and abietane phenolic diterpenoids. A simple procedure by cold evaporative crystallization to purify rosmarinic acid from these botanical species was also shown.

Covering: up to 2019The large and medicinally important tropical plant genus Plectranthus (Lamiaceae) was recently split into three separate genera on the basis of molecular and morphological evidence; Plectranthus sensu stricto, Coleus and Equilabium. We found striking differences between the diterpenoids which strongly support this taxonomic split. Coleus is characterised by abietanes oxygenated at C-14 such as royleanones, spirocoleons and acylhydroquinones, which could be useful chemotaxonomic markers to distinguish this genus from Plectranthus s.s. In contrast, the abietanes in Plectranthus s.s. lack C-14 oxygenation, but are often acylated with unusual acids. Equilabium species do not seem to produce diterpenoids. The structures of the nearly 240 abietanes so far reported from Coleus and Plectranthus and their distribution are presented. The aim of this Highlight is to provide an overview of the differences in diterpenoid diversity between these newly defined genera, which are relevant to predict which previously understudied species could hold untapped potential for their medicinal and other economic uses, and to underpin future research on how these plants have evolved to synthesise distinct abietane types.

Seven new (1-7) and 11 known diterpenoids were isolated and identified from Caryopteris aureoglandulosa. These diterpenoids were structurally determined by HRESIMS and NMR spectroscopic analyses, single-crystal X-ray diffraction, and ECD data. Structurally, aureoglandulosin A (1) is a highly oxygenated abietane diterpenoid with an unprecedented 7/6/6/5-ring system. Aureoglandulosins B (2) and C (3) represent naturally occurring new diterpenoids with an unusual 6/6/6/5-ring system. Additionally, the configurations of two known abietane diterpenoids 11 and 12 were determined by X-ray crystallographic data analysis for the first time. A plausible biosynthetic pathway for compounds 1-3 is proposed. The cytotoxicity of all isolates was evaluated, and compounds 1 and 11 exhibited significant cytotoxic activity against some cell lines with IC50 values in the range 1.6-8.2 μM.

Three previously undescribed ent-abietane-type diterpenoids, designated as 11β-hydroxy-14-oxo-17-al-ent-abieta-8(9),13(15)-dien-16,12β-olide (1), 11β,17-dihydroxy-12-methoxy-ent-abieta-8(14),13(15)...

Nine new and nineteen known compounds were isolated and identified from Rosmarinus officinalis under the guidance of bioassay and LCMS. They all belonged to abietane diterpenoids which enriched the types of compounds in R. officinalis, especially the discovery of a series of 20-norabietane diterpenoids (4, 6-9, and 26-27). The antioxidative damage activity of the compounds was tested on H2O2 damaged SH-SY5Y cells. Compounds 5, 6, and 7 presented moderate ability for promoting the growth of damaged cells. Compounds 10, 11, 13-20, 27, and 28 displayed a high antioxidative damage effect whose cell viability rates were more than 80%. The antioxidative damage effect of 11, 16, 18, and 20 were higher than that of EGCG (positive control) in which 11, 18, and 20 were the acetylated derivatives of carnosic acid (10), 7α-methoxy-isocarnosol (16), and carnosol (19), respectively. It suggested that 10-carboxyl/formyl of abietane diterpenoids was essential for maintaining the antioxidative damage activity and the adjacent hydroxyl groups on the benzene ring was less important for holding the bioactivity. These acetylated derivatives with high bioactivity and stability could be regarded as new sources of antioxidants or antioxidative damage agents being used in the food and medical industry.

Three new diterpenoids (1–3) (two abietane type diterpenoids and a paralianone type diterpenoid), together with four known compounds (4–7) were isolated from the whole plants of Euphorbia peplus. T...

The development of multidrug resistance (MDR) is a major cause of failure in cancer chemotherapy. Several abietane diterpenes with antitumoral activities have been isolated from Plectranthus spp. such as 6,7-dehydroroyleanone (DHR, 1) and 7α-acetoxy-6β-hydroxyroyleanone (AHR, 2). Several royleanone derivatives were prepared through hemisynthesis from natural compounds 1 and 2 to achieve a small library of products with enhanced anti-P-glycoprotein activity. Nonetheless, some derivatives tend to be unstable. Therefore, to reason such lack of stability, the electron density based local reactivity descriptors condensed Fukui functions and dual descriptor were calculated for several derivatives of DHR. Additionally, molecular docking and molecular dynamics studies were performed on several other derivatives to clarify the molecular mechanisms by which they may exert their inhibitory effect in P-gp activity. The analysis on local reactivity descriptors was important to understand possible degradation pathways and to guide further synthetic approaches toward new royleanone derivatives. A molecular docking study suggested that the presence of aromatic moieties increases the binding affinity of royleanone derivatives toward P-gp. It further suggests that one royleanone benzoylated derivative may act as a noncompetitive efflux modulator when bound to the M-site. The future generation of novel royleanone derivatives will involve (i) a selective modification of position C-12 with chemical moieties smaller than unsubstituted benzoyl rings and (ii) the modification of the substitution pattern of the benzoyloxy moiety at position C-6. This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in ACS Medicinal Chemistry Letters, copyright © American Chemical Society after peer review. To access the final edited and published work see [https://pubs.acs.org/doi/10.1021/acsmedchemlett.9b00642]. Related to: [http://ibiss-r.rcub.bg.ac.rs/handle/123456789/3817].

Callicarpa bodinieri is a Chinese traditional medicine herb with anti-inflammatory activity in clinic. Herein, we report two new 9,10-seco and etherified abietane diterpenoids bodinieric acids J and K (1 and 2) and one known compound (3) isolated from the leaves and twigs of this plant. Their chemical structures were elucidated by detailed spectrometry data analysis and DP4 + NMR calculation methods. Hypothetical biosynthetic pathways of 1−3 were preliminarily speculated. Compound 3 inhibited inflammasome activation and exhibited blockage of NLRP3 inflammasome activation at non-cytotoxic concentrations in vitro.

A novel cytochrome P450 from Tripterygium wilfordii, CYP81AM1, specifically catalyses the C-15 hydroxylation of dehydroabietic acid. This is the first CYP450 to be found in plants with this function. Cytochrome P450 oxygenases (CYPs) play an important role in the post-modification in biosynthesis of plant bioactive terpenoids. Here, we found that CYP81AM1 can catalyze the formation of 15-hydroxydehydroabietic acid by in vitro enzymatic reactions and in vivo yeast feeding assays. This is the first study to show that CYP81 family enzymes are involved in the hydroxylation of abietane diterpenoids. At the same time, we found that CYP81AM1 could not catalyse abietatriene and dehydroabietinol, suggesting that the occurrence of the reaction may be related to the carboxyl group. Through molecular docking and site mutations, it was found that some amino acid sites (F104, K107) near the carboxyl group had an important effect on enzyme activity, also suggesting that the carboxyl group played an important role in the occurrence of the reaction.

Nepeta bracteata Benth. is used clinically to treat tracheal inflammation, coughs, asthma, colds, fevers, adverse urination, and other symptoms, along with functions in clearing heat and removing dampness. However, there have been few studies characterizing the material basis of its efficacy. Therefore, the aim of this study was to screen for compounds with anti-inflammatory activities in N. bracteata Benth. Using silica gel, ODS C18, and Sephadex LH-20 column chromatography, as well as semipreparative HPLC, 10 compounds were separated from&nbsp, N. bracteata Benth. extract, including four new diterpenoids (1–4), one amide alkaloid (5), and five known diterpenoids (6–10). The structures of all the isolates were elucidated by HR-ESI-MS, NMR, and CD analyses. Using lipopolysaccharide (LPS)-stimulated RAW&nbsp, 264.7 cells, we investigated the anti-inflammatory&nbsp, activities of compounds 1–10. It is worth noting that all were able to inhibit nitric oxide (NO) production with IC50 values &lt, 50 μM and little effect on RAW 264.7 macrophage viability. Compounds 2 and 4 displayed remarkable inhibition with IC50 values of 19.2 and 18.8 μM, respectively. Meanwhile, screening on HCT-8 cells demonstrated that compounds 2 and 4 also had moderate cytotoxic activities with IC50 values of 36.3 and 41.4 μM, respectively, which is related to their anti-inflammatory effects.

Two new abietane diterpenoids (1,2), along with five known diterpenoids (3–7), were first isolated and purified from the stems of Clerodendrum bracteatum. The structures of the new compounds were established by extensive analysis of mass spectrometric and 1-D, 2-D NMR spectroscopic data. Their antioxidant activities were determined on DPPH radical scavenging and ABTS. The in vitro cytotoxic activities of the compounds were evaluated against the HL-60 and A549 cell lines by the MTT method.

Salvia corrugata Vahl. is an interesting source of abietane and abeo-abietane compounds that showed antibacterial, antitumor, and cytotoxic activities. The aim of the study was to obtain transformed roots of S. corrugata and to evaluate the production of terpenoids in comparison with in vivo root production. Hairy roots were initiated from leaf explants by infection with ATCC 15834 Agrobacterium rhizogenes onto hormone-free Murashige and Skoog (MS) solid medium. Transformation was confirmed by polymerase chain reaction analysis of rolC and virC1 genes. The biomass production was obtained in hormone-free liquid MS medium using Temporary Immersion System bioreactor RITA®. The chromatographic separation of the methanolic extract of the untransformed roots afforded horminone, ferruginol, 7-O-acetylhorminone and 7-O-methylhorminone. Agastol and ferruginol were isolated and quantified from the hairy roots. The amount of these metabolites indicated that the hairy roots of S. corrugata can be considered a source of these compounds.

Viruses cause widely transmitted diseases resulting in pandemic conditions. Currently, the world is being hit by the Covid-19 pandemic caused by the SAR-CoV-2 infection. Countries in the world are competing to develop antivirals to overcome this problem. Diterpene compounds derived from natural ingredients (plants, corals, algae, fungi, sponges) and synthesized products have potential as antivirals. This article summarizes the different types of diterpenes such as daphnane, tiglilane, kaurane, abietane, pimarane, labdane, dollabelane, jatrophane, dolastane, prenylated guaiane, tonantzitlolone, casbane, have antivirals activity such as targeting HIV, Coxsackie virus, herpes virus, hepatitis virus, influenza virus, Chikungunya virus, Zika virus, dengue virus, and SARS-CoV. Some compounds such as andrographolide and its derivatives show promising activity in inhibiting the influenza virus. Additionally, compounds such as pineolidic acid, forskolin, sugiol, and many other diterpene compounds showed anti-SAR-CoV activity. The diterpene compound class's high antivirals potential does not rule out the possibility that these compounds can also act as anti-SAR-CoV-2 drugs in the future., Antivirals, Covid-19, Diterpenes, Pandemic, SARS-CoV-2, Infectious diseases.

A phytochemical investigation of the leaves of the medicinal plant Isodon rubescens led to the isolation of the two new degraded abietane lactone diterpenoids rubesanolides F (1) and G (2). Their structures were elucidated based on the analyses of the HRESIMS and 1D/2D NMR spectral data, and their absolute configurations were determined by ECD spectrum calculations and X-ray single crystal diffraction methods. Compounds 1 and 2, with a unique γ-lactone subgroup between C-8 and C-20, were found to form a carbonyl carbon at C-13 by removal of the isopropyl group in an abietane diterpene skeleton. Rubesanolide G (2) is a rare case of abietane that possesses a cis-fused configuration between rings B and C. The two isolates were evaluated for their biological activities against two cancer cell lines (A549 and HL60), three fungal strains (Candida alba, Aspergillus niger and Rhizopus nigricans) and three bacterial strains (Escherichia coli, Staphylococcus aureus and Bacillus subtilis).

Two new dimeric abietane-type diterpenoids, 12-hydroxyabieta-8,11,13-trien-7α-yl 7β-hydroxyisopimara-8(14),15-diene-18-peroxoate (trivial name japonicinol A, 1) and 6α,7α-O-(7,8-secoabieta-9(11),13-diene-8,12-dioxo-7-ylidene)ferruginol (trivial name japonicinol B, 3), together with three known dimeric abietane-type diterpenoids, sugikurojin J (2), sugikurojin B (4) and formosaninol (5), were isolated from the bark of Cryptomeria japonica D. Don. Structure elucidation was accomplished by spectroscopic methods, mainly 1D and 2D NMR and HREIMS, as well as by comparison of their NMR data with those of related known analogues. At the concentration of 50 μM, compounds 1–5 inhibited xanthine oxidase activity by 31.3, 23.4, 18.7, 17.3 and 24.4%, respectively. In addition, compound 4 also inhibited angiotensin-converting enzyme (ACE) activity by 19.2%.

Background: Lamiaceae is one of the large families that occur worldwide and has species that are adaptable to almost all habitats and altitudes. Plectranthus is an important genus of Lamiaceae, recognized globally as an ornamental as well as a medicinal herb with good economic interest. The Plectranthus species possess antiseptic, vermicidal and purgative activities. Objective: The isolated compounds (1-3) from Plectranthus bishopianus were tested for their preliminary pharmacological evaluation for antibacterial, antioxidant and cytotoxic activities. Materials and Methods: The Plectranthus bishopianus leaves were collected from the Western Ghats of India. Extractions followed by isolation of the three compounds and structures were identified by NMR, HRMS. Results: The isolated compounds, 6,7-dehydroroyleanone (1), 6β-hydroxy-7α-methoxyroyleanone (2) and 6β, 7α-dihyroxyroyleanone (3) showed good antioxidant activity by DPPH method. The results of the cytotoxicity evaluation of the compounds (1-3) displayed excellent activity against MCF-7 cell line with IC50 values at 3.8 µg/mL, 3.85 µg/mL and 3.7 µg/mL respectively, which is more potent than the reference standard cisplatin. Conclusion: The structures of isolated compounds were confirmed by NMR, LC-HRMS and further pharmacological evaluation was accomplished. In addition, the isolates (1-3) were subjected to insilico molecular properties prediction by employing Molinspiration software for calculating their oral bioavailability and predicted to possess excellent oral bioavailability.

Celastrus orbiculatus is a medicinal plant belonging to the Celastraceae family. In this survey on the secondary metabolites of plants for obtaining antitumor substances, the chemical constituents of the stems of C. orbiculatus were investigated. Nortriptonoterpene (1), a new C19-norabietane diterpenoid, together with six other known abietane-type diterpenoids (2–7) and five known kaurane-type diterpenoids (8–12) were isolated and identified from the EtOAc extract of C. orbiculatus. Their structures were elucidated on the basis of extensive spectroscopic methods, including UV, IR, HR-ESI–MS, ECD, and NMR experiments, and by comparison with literature data. Compound 1 is a new C19-norabietane diterpenoid with 19 carbons. All compounds except for 10 and 11 were isolated from C. orbiculatus for the first time. The NMR data of 9 were reported for the first time. Compounds 1, 7 and 11 showed cytotoxicities against SGC-7901 with IC50 values of 63.2, 80.9 and 56.7 μM, respectively.

Two new ent-abietane diterpenoids, euphcopenoids A (1) and B (2), along with six known analogues (3 – 8), were isolated from the whole plants of Euphorbia helioscopia. Their structures were determined by various spectroscopic methods (MS, UV, IR, and NMR), and the absolute configurations of compounds 1 and 2 were determined by quantum chemical ECD calculations. All compounds were screened for the cytotoxicity against A549 and HEPG2 cancer cell lines, but were inactive.

The aerial parts of Salvia clinopodioides afforded abietanes 1a, 2a, and 3 (clinopodiolides A–C), two of which possess an unusual lactol moiety at C-19–C-20, together with an icetexane named clinopodiolide D (4a). Their structures were established by spectroscopic means, mainly 1H and 13C NMR, including 1D and 2D homo- and heteronuclear experiments. The antioxidant, antiprotozoal, and antidiarrheal effects of the isolates were evaluated. Compounds 2a and 3 showed better effects than α-tocopherol in the inhibition of lipid peroxidation with IC50 (μM) = 5.9 ± 0.1 and 2.7 ± 0.2, respectively, and moderate activity in the DPPH assay. All tested compounds showed moderate antiamoebic and antigiardial activity, as well as a good antipropulsive effect.

Cytotoxicity screenings have identified Plectranthus plants as potential sources of antitumor lead compounds. In this work, several extracts from Plectranthus madagascariensis were prepared using different solvents (acetone, methanol, and supercritical CO2) and extraction techniques (maceration, ultrasound-assisted, and supercritical fluid extraction), and their chemical composition was detailed using high-performance liquid chromatography with a diode array detector. The cytotoxic activity of the major compounds identified, namely, rosmarinic acid (1) and abietane diterpenes 7α,6β-dihydroxyroyleanone (2), 7α-formyloxy-6β-hydroxyroyleanone (3), 7α-acetoxy-6β-hydroxyroyleanone (4), and coleon U (5), was evaluated in a battery of human cancer cell lines, including breast (MDA-MB-231, MCF-7), colon (HCT116), and lung (NCI-H460, NCI-H460/R) cancer, and also in healthy lung (MCR-5) cells. Royleanone (3) was isolated for the first time from P. madagascariensis, and its full spectroscopic characterization (proton and carbon nuclear magnetic resonance) was accomplished. A high selectivity for lung cancer cells was observed for royleanones (2, 4) with selectivity indexes of 4.3 and 3.2, respectively. The observed results combined with literature data allowed the establishment of important structure–activity relationships for substituted royleanone abietanes, such as the requirement for an electron-donating group at positions 6 and/or 7 in the abietane skeleton, and an improved cytotoxic effect for substituents with log P values between 2 and 5.

Rosemary and sage species from Lamiaceae contain high amounts of structurally related but diverse abietane diterpenes. A number of substances from this compound family have potential pharmacological activities and are used in the food and cosmetic industry. This has raised interest in their biosynthesis. Investigations in Rosmarinus officinalis and some sage species have uncovered two main groups of cytochrome P450 oxygenases that are involved in the oxidation of the precursor abietatriene. CYP76AHs produce ferruginol and 11-hydroxyferruginol, while CYP76AKs catalyze oxidations at the C20 position. Using a modular Golden-Gate-compatible assembly system for yeast expression, these enzymes were systematically tested either alone or in combination. A total of 14 abietane diterpenes could be detected, 8 of which have not been reported thus far. We demonstrate here that yeast is a valid system for engineering and reconstituting the abietane diterpene network, allowing for the discovery of novel compounds with potential bioactivity.

Bioactivity-guided isolation of the cultures of the endophytic fugus Xylaria sp. XC-16 residing in a deciduous tree Toona sinensis led to the discovery of four new allelochemicals (1-4), including three cytochalasins, epoxycytochalasin Z17 (1), epoxycytochalasin Z8 (2), and epoxyrosellichalasin (3), and an abietane-type diterpenoid, hydroxyldecandrin G (4), along with four known analogues, 10-phenyl-[12]-cytochalasins Z16 (5) and Z17 (6), cytochalasin K (7), and cytochalasin E (8). The structures of these compounds were elucidated by comprehensive spectroscopic methods, and their absolute configurations were determined by electronic circular dichroism (CD) and X-ray diffraction. All of the chemicals were tested for their allelopathic effects on turnip ( Raphanus sativus) and wheat ( Triticum aestivum). Notably, compounds 3, 4, and 7 strongly inhibited wheat shoot elongation, and compounds 5, 7, and 8 inhibited wheat root elongation, showing comparable IC50 values to the positive control glyphosate. Meanwhile, compound 8 was a potential inhibitor on turnip root elongation, with an IC50 value of 1.57 ± 0.21 μM, which was 50-fold more potent than glyphosate. Nevertheless, compounds 5 and 7 stimulated turnip shoot elongation at lower concentrations.

Twenty-four diterpenoids of abietane family, including thirteen undescribed compounds and eleven known ones, were isolated from the leaves of Leucosceptrum canum. Their structures were elucidated by comprehensive spectroscopic analyses (including 1D and 2D-NMR and HRMS), and in the case of 15-hydroxy-abieta-8,11,13-trien-3-one by single-crystal X-ray diffraction. Their frameworks are highly diversified, involving normal abietane, 9,10-epoxy-9,10-seco-abietane, 18(4 → 3)-abeo-abietane, 3,4-seco-18(4 → 3)-abeo-abietane, and 16-nor-abietane. Selected compounds were evaluated for their cytotoxic activity against three human tumor cell lines, NCI-H1975, HepG2 and MCF-7. Among them, 3β-hydroxy-abieta-8,13-diene, 3β-hydroxy-abieta-8,11,13,15-tetraene, and 3β-hydroxy-9,10-epoxy-9,10-seco-abieta-8,11,13-triene exhibited moderate cytotoxicity against all three cell lines with IC50 values ranging from 8.11 to 50.73 μM, while 3α-hydroxy-abieta-8,11,13,15-tetraene, 3β-hydroxy-abieta-8,11,13,15-tetraen-7-one, and 15-hydroxy-18(4 → 3)-abeo-abieta-3,8,11,13-tetraene were selectively active with IC50 values ranging from 28.80 to 71.29 μM.

Plant-derived diterpenoids are commonly used as conifer-specific biomarkers and for chemotaxonomic assignment or confirmation. Numerous studies have reported on the utility of diterpenoids as chemotaxonomic indicators, but few have quantitatively analyzed diterpenoid concentrations, especially with respect to conifer phylogeny. In addition, the carbon isotope values (δ13C) of diterpenoids provide a means to track conifer-specific δ13C values, which is useful for tracking water availability and the carbon cycle. To expand on previous work, we measured diterpenoid concentrations and carbon isotopes of 43 conifer species, and Ginkgo biloba, collected at the University of California Botanical Garden at Berkeley. In this collection, all extant conifer families and almost two-thirds of extant genera are present, including many subtropical and Southern Hemisphere groups that were once common and widespread components of fossil assemblages. Overall, we found diterpenoid concentrations were highly variable among species and families. Despite this variability, there is coarse family-level phylogenetic structuring with the lowest concentrations in Pinaceae. When diterpenoid concentrations are fitted to a model of trait evolution (Brownian motion), we however find that there is no phylogenetic signal. In contrast, when terpenoids are analyzed by the proportion of diterpenoid compound structure classes (abietanes, labdanes, pimaranes, tetracyclics, and totarols/sempervirol), there was significant phylogenic signal for the abietane and tetracyclic structures. Diterpenoid biosynthetic carbon isotope fractionation, as expressed between diterpenoids and leaf tissue (editerpenoid), also contained a phylogenetic signal, as well as the broad phylogenetic structuring observed in total diterpenoid concentrations. Overall, these results indicate that the Pinaceae is unique among conifer clades with respect to terpenoid structure classes, concentrations and editerpenoid. When diterpenoids are applied to taxonomic assignment of fossils, it would be useful to combine several traits (concentration, proportion, and editerpenoid). In this context, it should be possible to broadly distinguish three major conifer groups: Cupressaceae, Podocarpaceae and Pinaceae. However, based on these results, we recommend against assuming that closely related species have similar diterpenoid compositions.

Coleus amboinicus Lour., Lamiaceae, is a perennial herb that is native to Indonesia and also cultivated in Africa, Asia and Australia. The major phytochemicals responsible for its bioactivity are rosmarinic acid (RA) and its analogues, flavonoids and abietane diterpenoids. The possibility of cultivation in a colder climate would extend the use of this herb and provide new opportunities to herb growers and livestock farmers. Our study to compare feed value and phytochemical composition of C. amboinicus plants cultivated in its original region, Indonesia, and in Poland. The crude protein content was significantly higher in plants cultivated in Indonesia compared to those cultivated in Poland—21% and 13% of dry matter, respectively. The higher ADF contents were detected in C. amboinicus cultivated in Indonesia, 38–41%, in comparison to 34% in plants cultivated in Poland. The phytochemical composition was also significantly influenced by the cultivation location. Polish samples were higher in polyphenols (RA and its analogues), and also had 1.5–2-fold higher antioxidant potential, as measured by DPPH scavenging, phosphomolybdenum reduction and Fenton reaction driven lipid peroxidation. The Indonesian samples contained more diterpenoid compounds, such as dihydroxyroyleanone, and the sum of terpenoids was ca. 10 times higher than in samples from Poland (15.59–23.64 vs. 1.87 µg/g of extracts). In conclusion, C. amboinicus is suitable for cultivation in non-optimal climatic conditions but some nutritional properties and bioactivity are significantly affected.

As part of our studies on antiprotozoal activity of approved herbal medicinal products, we previously found that a commercial tincture from Salvia officinalis L. (common Sage, Lamiaceae) possesses high activity against Trypanosoma brucei rhodesiense (Tbr), causative agent of East African Human Trypanosomiasis. We have now investigated in detail the antitrypanosomal constituents of this preparation. A variety of fractions were tested for antitrypanosomal activity and analyzed by UHPLC/+ESI QqTOF MS. The resulting data were used to generate a partial least squares (PLS) regression model that highlighted eight particular constituents that were likely to account for the major part of the bioactivity. These compounds were then purified and identified and their activity against the pathogen tested. All identified compounds (one flavonoid and eight diterpenes) displayed significant activity against Tbr, in some cases higher than that of the total tincture. From the overall results, it can be concluded that the antitrypanosomal activity of S. officinalis L. is, for the major part, caused by abietane-type diterpenes of the rosmanol/rosmaquinone group.

Four undescribed ent-kaurane diterpenoids, wilkaunoids A − D (1–4), and three undescribed abietane diterpenoids, wilabinoids A − C (13–15), along with thirteen known ones (5–12 and 16–20), were isolated from Tripterygium wilfordii. Their structures were elucidated by extensive spectroscopic methods, electronic circular dichroism calculation, and X-ray diffraction analysis. Compounds 1 and 2 were a pair of C-19 epimers of ent-kaurane diterpenoids, featuring a rare 19,20-epoxy-19,20-dimethoxy-kaurane fragment. Compound 3 possessed a rare naturally occurring 1,3-dioxacyclohexane moiety. Compounds 13 and 15 represented the first example of abietane diterpenoids with an isovalerate substitution from the genus of Tripterygium. The possible biosynthetic pathways of 1–3 were postulated. The effect of 1–20 on nitric oxide production was examined in lipopolysaccharide-stimulated RAW 264.7 cells. Abietane diterpenoid quinones 7–13 (IC50: 1.9–10.2 μM) exhibited the significant activity to inhibit nitric oxide production versus positive control (NG-monomethyl- l -arginine acetate salt, IC50 = 24.9 μM). The structure activity relationship of 7–13 in inhibiting nitric oxide production was then discussed. The most potent 7 and 8 were found to significantly suppress the expression of cyclooxygenase-2 and inducible nitric oxide synthase proteins, showing a good anti-inflammatory potential. The findings provided some valuable insights for the discovery and structural modification of abietane diterpenoids towards anti-inflammatory lead compounds.

Plectranthus species (Lamiaceae) have been employed in traditional medicine and this is now validated by the presence of bioactive abietane-type diterpenoids. Herein, sixteen Plectranthus acetonic extracts were prepared by ultrasound-assisted extraction and their biological activity was screened. The antimicrobial activity of each extract was screened against yeasts, and Gram-positive and Gram-negative bacteria. The P. hadiensis and P. mutabilis extracts possessed significant activity against Staphylococcus aureus and Candida albicans (microdilution method). Moreover, all extracts showed antioxidant activity using the DPPH method, with P. hadiensis and P. mutabilis extracts having the highest scavenging activities. Selected by the Artemia salina model, P. hadiensis and P.ciliatus possessed low micromolar anti-proliferative activities in human colon, breast, and lung cancer cell lines. Furthermore, the most bioactive extract of P. hadiensis leaves and the known abietane diterpene, 7α-acetoxy-6β-hydroxyroyleanone isolated from this plant, were tested against the aggressive type triple negative breast cancer (MDA-MB-231S). P. hadiensis extract reduced the viability of MDA-MB-231S cancer cell line cells, showing an IC50 value of 25.6 µg/mL. The IC50 value of 7α-acetoxy-6β-hydroxyroyleanone was 5.5 µM (2.15 µg/mL), suggesting that this lead molecule is a potential starting tool for the development of anti-cancer drugs.

[EN] The abietane-type diterpenoids are significant bioactive compounds exhibiting a varied range of pharmacological properties. In this study, the first synthesis and biological investigation of the new abietane-diterpenoid (+)-4-epi-liquiditerpenoid acid (8a) together with several of its analogs are reported. The compounds were generated from the readily available methyl callitrisate (7), which was obtained from callitrisic acid present in Moroccan Sandarac resin. A biological evaluation was conducted to determine the effects of the different functional groups present in these molecules, providing basic structure-activity relationship (SAR) elements. In particular, the ferruginol and sugiol analogs compounds 10-16 were characterized by the presence of a phenol moiety, higher oxidization states at C-7 (ketone), and the hydroxyl, methyl ester or free carboxylic acid at C19. The biological profiling of these compounds was investigated against a panel of six human solid tumor cell lines (HBL-100, A549, HeLa, T-47D, SW1573 and WiDr), four parasitic Leishmania species (L. donovani, L. infantum, L. guyanensis and L. amazonensis) and two malaria strains (3D7 and K1). Furthermore, the capacity of the compounds to modulate gamma-aminobutyric acid type A (GABA(A)) receptors (alpha(1)beta(2)gamma(2s)) is also described. A comparison of the biological results with those previously reported of the corresponding C18-functionalized analogs was conducted., This research was funded by Spanish National Research Council: 201680I008; Austrian Science Fund: FWF W 1232; American Lebanese Syrian Associated Charities. Santander Bank. Spanish Ministry of Science: PGC2018-094503-B-C22 and "The APC was funded by MDPI".

In the present study, activity-guided isolation and structural elucidation of antioxidant secondary metabolites of ethanol extracts prepared from the root and aerial parts of Salvia rosifolia and Salvia cerino-pruinosa var. elazigensis species was aimed. The ethanol extracts of the species were fractionated and the antioxidant capacities of the fractions were determined by DPPH-free radical and ABTS-cation radical scavenging activity, and cupric-reducing antioxidant capacity (CUPRAC) assays. Isolation studies of the fractions with high antioxidant activities were carried out. Thirty nine secondary metabolites of known structure were isolated from the active extracts. 17 of the isolated compounds are in phenolic-flavonoid structure, 4 of them are in fatty acid structure, 7 of them are in abietane type diterpene structure, 2 of which are paraquinone and 5 of which are in aromatic structure, 8 of them are in triterpene structure, 2 of which are ursane, 2 of which are oleane and 4 of which are lupane structure, and 3 of them are in steroid structure. The structures of the isolated compounds were determined by UV, IR, H-1- and C-13-NMR-(APT), HMQC-HMBC, LCMS-IT/TOF and GC-MS techniques. It was determined that phenolic compounds among the isolated compounds were more active than terpenoid compounds in all three methods.

Summary The geoterpenoid composition of the Paleocene sediments from the Barsingsar lignite mine of Bikaner-Nagaur Basin (Rajasthan) have been studied with the help of gas chromatography-mass spectrometry (GC-MS) to understand their botanical origin. The terpenoids include sesquiterpenoids, diterpenoids and few triterpenoids. The sesquiterpenoids and terpenoids indicate higher plant-derived. The diterpenoid primarly comprising of abietane, phyllocladane, kaurane, pimarane/isopimarane and podocarpane-class compounds show affinities to Southern Hemisphere conifer families, Podocarpaceae and Araucariaceae. The tetracyclic diterpenoids include 18-norkaurane, ent-beyerane, ent-16s(H)-kaurane and 16a(H)-phyllocladane. The tricyclic diterpenoid, rosane and its derivative are identified. Exceptional void of phenolic abietanes and labdane derivatives rules out the probability of Pinaceae being the source. Low abundance in pentacyclic terpenoids like oleananes and their degraded forms suggest a negligible angiosperm contribution . The average value of pr/phy in the realm is 1.8 indicating dysaerobic depositional setting. The ar-AGI values for the samples range from 0.01 to 1. The t-AGI 1 and t-AGI 2 values range from 0.009 to 1.23 and 0.002 to 0.34 respectively indicating low angiosperm input. This work provided evidence of the occurrence of a gymnosperm dominated tropical rainforest as refugia in the midst of emerging angiosperms and a probable clue to biotic exchange out-of-India during the Paleocene.

The roots of Salvia spinosa L. (Lamiaceae) were extracted with hexane, dichloromethane (DCM) and ethyl acetate. The DCM extract exhibited cytotoxic activity (IC50 32.7 µg/mL) against MFC-7 breast cancer cell line in MTT colorimetric bioassay. Ferruginol (1), taxodione (2), 12-deoxy-6-hydroxy-6,7-dehydroroyleanone (3), 14-deoxycoleon U (4), 15-deoxyfuerstione (5) and taxodone (6) were isolated from the DCM roots extract. Their structures were elucidated by a combination of spectroscopic analyses including EIMS and 1H- and 13C NMR spectra. The cytotoxicity of compound 3 was determined against MCF-7 and K562 cell lines and compared with the other compounds. A pharmacophore model was built based on potent input compounds to resolve important pharmacophore features responsible for cytotoxic activity of the isolated compounds. Salvia spinosa produces cytotxic abietane diterpenoids

Quorum-sensing (QS) is a regulatory mechanism in bacterial communication, important for pathogenesis control. The search for small molecules active as quorum-sensing inhibitors (QSI) that can synergize with antibiotics is considered a good strategy to counteract the problem of antibiotic resistance. Here the antimicrobial labdane diterpenoids sclareol (1) and manool (2) extracted from Salvia tingitana were considered as potential QSI against methicillin-resistant Staphylococcus aureus. Only sclareol showed synergistic activity with clindamycin. The quantification of these compounds by LC–MS analysis in the organs and in the calli of S. tingitana showed that sclareol is most abundant in the flower spikes and is produced by calli, while manool is the major labdane of the roots, and is abundant also in the leaves. Other metabolites of the roots were abietane diterpenoids, common in Salvia species, and pentacyclic triterpenoids, bearing a γ-lactone moiety, previously undescribed in Salvia. Docking simulations suggested that 1 and 2 bind to key residues, involved in direct interactions with DNA. They may prevent accessory gene regulator A (AgrA) binding to DNA or AgrA activation upon phosphorylation, to suppress virulence factor expression. The antimicrobial activity of these two compounds probably achieves preventing upregulation of the accessory gene regulator (agr)-regulated genes.

In this work, the sawmill waste from Picea abies debarking was considered as source of valuable phytoconstituents. The extraction was performed using different ethanol/water mixtures, and characterization was obtained by LC-MSn. This latter revealed flavonoid glycosides, lignans, and procyanidins. Extraction with organic solvents (dichloromethane and methanol) and chromatographic separations of the obtained extracts by silica column followed by semi-preparative HPLC led to the isolation of polyphenols and terpenoids such as 21α-metoxy-serrat-14-en-3-one, 21α-hydroxy-serrat-14-en-3-one, pinoresinol, dehydroabietic acid, 15-hydroxy-dehydroabietic acid, 7-oxo-dehydroabietic acid, pimaric acid, 9β-pimara-7,15-dien-19-ol, 13-epi-manoyl oxide, taxifolin-3′-O-glucopyranoside, trans-astringin, and piceasides. Piceaside V and 9β-pimara-7-keto-19β-olide, two novel compounds identified for the first time in P. abies bark, were isolated, and their structures were elucidated using 1D and 2D NMR and MS techniques. The polyphenolic composition of the methanolic portion was also investigated using LC-MSn, and the piceaside content was estimated. To assess the antioxidant activity of main constituents, semi-preparative HPLC was performed on the methanolic extract, and the obtained fractions were assayed by using the DPPH test. Overall, this work shows the potential usefulness of P. abies bark as a source of valuable phytochemicals.

Five undescribed abietane diterpenoids, dracocephalumoids A–E, together with six known analogues were isolated from the aqueous EtOH extract of aerial parts of Dracocephalum moldavica L.. The structures were elucidated through extensive analysis of spectroscopic data, and their absolute configurations were established by Mosher's method and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculation. Cell-based anti-inflammatory assays displayed that dracocephalumoid A, uncinatone, trichotomone F and caryopterisoid C showed potent suppressive effects against TNF-α, IL-1β or NO production in LPS-induced RAW 264.7 cells, with IC50 values ranging from 1.12 to 5.84 μM. The structure-activity relationship of these compounds was also discussed.

Salvia species are frequently used in traditional medicine and are a source of diterpenoid antioxidants. In this study, the hydroperoxide radical scavenging activity of seven known abietane diterpenoids (ADs), isolated from Salvia barrelieri, are investigated using a quantum chemical approach. The ADs are 7-oxoroyleanone-12-methyl ether (1), 7a-acetoxyroyleanone-12-methyl ether (2), royleanone (3), horminone (4), 7-acetylhorminone (5), cryptojaponol (6), and inuroyleanol (7). It was found that formal hydrogen transfer is the main mechanism of the antiradical activity of these ADs in nonpolar environments, whereas the single electron transfer mechanism of anion states is favored in aqueous environment. The antioxidant activity of compounds 1-5 involves H-abstraction at the C7(15)-H bonds whereas for the compounds 6 and 7 the H abstraction takes place at the O12-H bond. The HOO• scavenging activity of compounds 1-5 is minor in all of the studied media, however 6 and 7 exhibit excellent antiradical activity in aqueous solution. Remarkably, the HOO• scavenging activity of compound 7 is substantially higher than that of Trolox, the reference antioxidant: the calculated rate constant was 122.3 times higher in polar and 6.1 times higher in nonpolar environments, respectively. Consistently 7 is a promising radical scavenger in physiological environments.

The life-long and life-threatening Chagas disease is one of the most neglected tropical diseases caused by the protozoan parasite Trypanosoma cruzi. It is a major public health problem in Latin America, as six to seven million people are infected, being the principal cause of mortality in many endemic regions. Moreover, Chagas disease has become widespread due to migrant populations. Additionally, there are no vaccines nor effective treatments to fight the disease because of its long-term nature and complex pathology. Therefore, these facts emphasize how crucial the international effort for the development of new treatments against Chagas disease is. Here, we present the in vitro and in vivo trypanocidal activity of some oxygenated abietane diterpenoids and related compounds. The 1,4-benzoquinone 15, not yet reported, was identified as a fast-acting trypanocidal drug with efficacy against different strains in vitro and higher activity and lower toxicity than benznidazole in both phases of murine Chagas disease. The mode of action was also evaluated, suggesting that quinone 15 kills T. cruzi by inducing mitochondrion-dependent necrosis through a bioenergetics collapse caused by a mitochondrial membrane depolarization and iron-containing superoxide dismutase inhibition. Therefore, the abietane 1,4-benzoquinone 15 can be considered as a new candidate molecule for the development of an appropriate and commercially accessible anti-Chagas drug.

With an estimated 28,137 recorded medicinal plants species, it is not surprising that over 80% of the world’s population rely on traditional herbal medicines as their primary source of healthcare. In recent years, herbal medicinal use in the West has seen a resurgence, as an alternative and complementary approach to treating and preventing disease. Plectranthus species (Lamiaceae family) have widespread ethnobotanical and traditional uses, including in southern Africa to treat listeriosis, tuberculosis-related problems and skin diseases. The extensive use of these plants suggests this genus may be highly promising for the discovery of medicinal compounds, including antitumour, antimicrobial and antioxidant compounds. This review enumerates the abietane diterpene secondary metabolites, isolated to date, from the extracts and fractions of Plectranthus ecklonii Benth. Using the search terms, ‘Plectranthus ecklonii’, ‘parvifloron D’, ‘parvifloron E’, ‘parvifloron F’ and ‘sugiol’, databases, including PubMed, Web of Science and ScienceDirect, were examined. This work focuses on the documented bioactivity of the isolated active compounds, parvifloron D, E, F and sugiol, in order to consider their potential for pharmaceutical development of novel drugs.

Diabetes mellitus (DM) is one of the most dangerous metabolic diseases with a high rate of mortality worldwide. It is well known that insulin resistance and deficiency in insulin production from pancreatic &beta, cells are the main characteristics of DM. Due to the detrimental side effects of the current treatment, there is a considerable need to develop new effective antidiabetic drugs, especially alpha-glucosidase and alpha-amylase inhibitors with lesser adverse effects. These inhibitors are known to be directly involved in the delay of carbohydrate digestion, resulting in a reduction of glucose absorption rate and, consequently, reducing the postprandial rise of plasma glucose, which can reduce the risk of long-term diabetes complications. Furthermore, natural products are well-known sources for the discovery of new bioactive compounds that can serve as scaffolds for drug discovery, including that of new antidiabetic drugs. The phytochemical investigation of Salvia aurita collected from Hogobach Pass, Eastern Cape Province, South Africa (SA), yielded four known abietane diterpenes namely carnosol (1), rosmanol (2), 7-methoxyrosmanol (3), 12-methoxycarnosic acid (4), and one flavonoid named 4,7-dimethylapigenin (5). Structural characterization of these isolated compounds was conducted using 1 and 2D NMR, in comparison with reported spectroscopic data. These compounds are reported for the first time from S. aurita. The biological evaluation of the isolated compound against alpha-glucosidase exhibited strong inhibitory activities for 3 and 2 with the half maximal inhibitory concentration (IC50) values of 4.2 &plusmn, 0.7 and 16.4 &plusmn, 1.1 &micro, g/mL respectively, while 4 and 1 demonstrated strong alpha-amylase inhibitory activity amongst the isolated compounds with IC50 values of 16.2 &plusmn, 0.3 and 19.8 &plusmn, 1.4 &micro, g/mL. Molecular docking analysis confirms the strong inhibitory activity of 3 against alpha-glucosidase. Additionally, excellent antioxidant capacities were displayed by 2, 1, and 3, respectively, with oxygen radical absorbance capacity (ORAC) (25.79 &plusmn, 0.01, 23.96 &plusmn, 23.94 &plusmn, 0.02) mM Trolox equivalent (TE)/g, 1 and 2 as ferric-ion reducing antioxidant power (FRAP) (3.92 &plusmn, 0.002, 1.52 &plusmn, 0.002) mM ascorbic acid equivalent (AAE)/g, 5 and 2 as Trolox equivalent absorbance capacity (TEAC) (3.19 &plusmn, 0.003, 2.06 &plusmn, 0.003) mM TE/g. The methanolic extract of S. aurita is a rich source of abietane diterpenes with excellent antioxidant and antidiabetic activities that can be useful to modulate oxidative stress and might possibly be excellent candidates for the management of diabetes. This is the first scientific report on the phytochemical isolation and biological evaluation of the alpha-glucosidase and alpha-amylase inhibitory activities of Salvia aurita.

Three undescribed dammarane-type saponins, russelliinosides A-C, together with a common sterol (β-sitosterol), an abietane diterpenoid (18-hydroxyferruginol), two oleane triterpenoids (daturaolone and oleanolic acid), an ursane triterpenoid (ursolic acid) as well as three 5-hydroxyflavones (cirsimaritin, eupatorin, and salvigenin) were isolated from a dichloromethane extract of the aerial parts of Salvia russellii Benth. The chemical structures of the aforementioned compounds were characterized, using detailed spectroscopic analyses, including high-resolution mass spectrometry and 1D and 2D NMR (1H–1H COSY, TOCSY, HSQC, HMBC and NOESY) spectroscopy as well as physicochemical properties. Cytotoxic effects of S. russellii extract and the three isolated russelliinosides were tested against MCF-7 human breast and A549 lung cancer, as well as non-cancer NIH/3T3 cells using MTT reduction assay. Russelliinosides A and B exhibited cytotoxic activities with IC50 values of 7.1 and 30.7 μg/ml against MCF-7 and 33.9 and 69.4 μg/ml against A549 cells, respectively, while russelliinoside C did not show cytotoxicity against cancer cells. On the other hand, russelliinoside A showed an IC50 value of 31.5 μg/ml against NIH/3T3 cells, while russelliinosides B and C had no effect on the viability of these non-cancer cells.

The prevalence of diabetes mellitus (DM), considered one of the most common metabolic disorders, has dramatically increased and resulted in higher rate of morbidity and mortality around the world, in the past decade. It is well known that insulin resistance in target tissues and a deficiency in insulin secretion from pancreatic β-cells are the main characteristic of type 2 diabetes. The aim of this study was the bio-evaluation of compounds isolated from three selected plant species; namely, Salvia africana-lutea, Leonotis ocymifolia and Plectranthus madagascariensis, for their glucose uptake ability. Methanolic extracts were produced from the arterial part of each plant. Compounds were identified using different spectroscopic techniques. The glucose uptake ability of each compound was then evaluated in mammalian cells using 2-deoxyglucose-6-phosphate. The cytotoxicity of each compound was established via the MTT assay. Chromatographic purification of the three plant species yielded fifteen pure terpenoids. Compounds 1 (p = 0.0031), 8 (p = 0.0053), and 6 (p = 0.0086), showed a marked increase in glucose uptake, with p values of p=0.0031, p=0.0053 and p=0.0086, respectively. Additionally, 1, 4 and 6 exhibited cytotoxicity toward mammalian tissue with a decrease in cell viability of ~70%, ~68% and ~67%, respectively. The results suggested that several compounds demonstrated a marked increase in glucose uptake while two of the compounds exhibited signs of cytotoxicity. It may, therefore, be suggested that these compounds be considered as potential candidates for novel plant-derived alternative therapies in the treatment of type 2 diabetes.

A total of twenty abietane quinone diterpenoids including ten new ones (1-10) were isolated from the roots extract of Salvia deserta. Their chemical structures were delineated by extensive spectrometric and spectroscopic techniques including HRESIMS, NMR, UV, IR, and single-crystal X-ray diffraction analysis, calculated 13C NMR-DP4+ analysis, calculated ECD, and Mo2(OAc)4-induced ECD. The absolute configurations of salvidesertone A (1), 8α,9α-epoxy-6-deoxycoleon U (18), and 7,20-epoxyroyleanone (19) were determined by single-crystal X-ray diffraction analysis. Salvidesertone A (1) represents the first example of a 9-hydroxyabieta-7(8)-ene quinone diterpenoid. This is the first report of the crystal structures of 8α,9α-epoxy-6-deoxycoleon U (18) and 7,20-epoxyroyleanone (19). Abietane quinone diterpenoids 1, 2, and 4-20 were evaluated for their antiproliferative activities against five cancer cell lines A-549, SMMC-7721, SW480, MCF-7, and HL-60 and a normal epithelial cell line BEAS-2B in vitro. Salvidesertones E (8) and F (9) selectively inhibited the proliferation of A-549, SMMC-7721, and SW480 cancer cell lines. Importantly, salvidesertones E (8) and F (9), horminone (13), taxoquinone (14), 7α-O-methylhorminone (15), and 8α,9α-epoxy-6-deoxycoleon U (18) showed more potent antiproliferative effects against A-549 than the positive control cis-platin. A preliminary structure-activity relationship for the antiproliferative effects of abietane quinone diterpenoids 1-20 was discussed.

Ethnopharmacological relevance Plectranthus madagascariensis (Pers.) Benth. is an indigenous aromatic South African plant species that are traditionally used to treat various dermatological and respiratory ailments. Aim of the study Three varieties of P. madagascariensis exist in South Africa, namely, Plectranthus aliciae (Codd) van Jaarsv. & T.J. Edwards, Plectranthus ramosior (Benth.) Van Jaarsv. and Plectranthus madagascariensis (Pers.) Benth var. madagascariensis. This article summarizes the documented ethnobotanical uses and research which has been conducted to date on the chemical constituents and biological effects of P. madagascariensis and its varieties. This review aimed to investigate and highlight the lack scientific reports of the potential activity of these varieties based on their traditional usage and to emphasise the need for further investigation of the benefits of P. madagascariensis and its varieties. Materials and methods Extensive database retrieval using platforms not limited to but including Google Scholar, ScienceDirect and PubMed, was performed by using keywords such as “Plectranthus madagascariensis” “Plectranthus madagascariensis var. aliciae”, “Plectranthus aliciae”, “Plectranthus ramosior”, “Plectranthus madagascariensis var. ramosior” and “Plectranthus hirtus” In addition, relevant books and digital documentation were consulted to collect all available scientific literature to provide a comprehensive review. Results Several studies have reported the traditional usage of P. madagascariensis for the treatment of diseases related to the respiratory system such as coughs, colds and asthma as well as dermatological disorders associated with wounds and inflammation. Whilst there are no reports on the traditional usage of P. madagascariensis varieties to treat other maladies, several other species within the genus are used in other traditional practices. Plectranthus ramosior is used as a toxin for fishing. In literature, seven major phytochemical compounds have been identified from P. madagascariensis. Its extract and essential oil contain polyphenols, abietane diterpenes and abietane diterpenes with a quinone moiety. The extracts and major chemical constituents of P. madagascariensis and its major phytochemicals have reported activity against several biological targets. Reports relating to the antibacterial activity of P. madagascariensis against microbes associated with tuberculosis and wound infections has been consistent and correlates with the documented traditional usage of the plant. Literature reported on the antibacterial activity of P. aliciae targeting bacteria associated with wound infections and lung cancer cells. No further literature reports of the biological activity of the other P. madagascariensis varieties have been found. Other noteworthy biological activities reported in the literature of P. madagascariensis and its compounds include their activities against targets of Alzheimer's disease and breast cancer, in particular. This activity is not related to the traditional usage of the plant. Conclusion Plectranthus madagascariensis and its compounds have been proven to be effective in treating a range of maladies. Based on the extensive literature on this plant, it can be concluded that numerous in vitro pharmacological activities of P. madagascariensis have been reported. However, there is a lack of information available for this species with regards to its in vivo data including both pre-clinical and clinical studies. Since the extract of P. madagascariensis and its isolated compounds have displayed noteworthy anticancer potential, we recommend further investigation of pharmacokinetic studies to be included in future research.