Synthesis of the natural product prattinin A and some new derivatives has been achieved using abietic acid. The final products and a selection of intermediates were evaluated for their antibacterial ...activity against three human pathogenic bacteria:
,
, and
. The results showed that the antibacterial activity varies depending on the chemical structure of the compounds. Notably, compound
exhibited the most potent activity against
and
with a minimal inhibitory concentration (MIC) of 11.7 µg/mL, comparable to that of the standard antibiotic ciprofloxacin, and strong activity against
, with an MIC of 23.4 µg/mL. Furthermore, we assessed the stability of these derivative compounds as potential antimicrobial agents and determined their interactions with the crystal structure of the protein receptor mutant TEM-12 from
(pdb:1ESU) using molecular docking via UCSF Chimera software 1.17.3. The results suggest that
has potential as a natural antibiotic agent.
Pterolobirin H (3), a cassane diterpene isolated from the roots of Pterolobium macropterum, exhibits important anti-inflammatory and anticancer properties. However, its relatively complex tetracyclic ...structure makes it difficult to obtain by chemical synthesis, thus limiting the studies of its biological activities. Therefore, we present here a short route to obtain a rational simplification of pterolobirin H (3) and some intermediates. The anti-inflammatory activity of these compounds was assayed in LPS-stimulated RAW 264.7 macrophages. All compounds showed potent inhibition of NO production, with percentages between 54 to 100% at sub-cytotoxic concentrations. The highest anti-inflammatory effect was shown for compounds 15 and 16. The simplified analog 16 revealed potential NO inhibition properties, being 2.34 higher than that of natural cassane pterolobirin H (3). On the other hand, hydroxyphenol 15 was also demonstrated to be the strongest NO inhibitor in RAW 264.7 macrophages (IC50 NO = 0.62 ± 0.21 μg/mL), with an IC50NO value 28.3 times lower than that of pterolobirin H (3). Moreover, the anticancer potential of these compounds was evaluated in three cancer cell lines: HT29 colon cancer cells, Hep-G2 hepatoma cells, and B16-F10 murine melanoma cells. Intermediate 15 was the most active against all the selected tumor cell lines. Compound 15 revealed the highest cytotoxic effect with the lowest IC50 value (IC50 = 2.45 ± 0.29 μg/mL in HT29 cells) and displayed an important apoptotic effect through an extrinsic pathway, as evidenced in the flow cytometry analysis. Furthermore, the Hoechst staining assay showed that analog 15 triggered morphological changes, including nuclear fragmentation and chromatin condensation, in treated HT29 cells. Finally, the in silico studies demonstrated that cassane analogs exhibit promising binding affinities and docking performance with iNOS and caspase 8, which confirms the obtained experimental results.
A set of thirteen cassane-type diterpenes was synthesized and an expedient synthetic route was used to evaluate 14-desmethyl analogs of the most active tested cassane. The anti-inflammatory ...activities of these 13 compounds were evaluated on a lipopolysaccharide (LPS)-activated RAW 264.7 cell line by inhibition of nitric oxide (NO) production, some of them reaching 100% NO inhibition after 72 h of treatment. The greatest anti-inflammatory effect was observed for compounds 16 and 20 with an IC50 NO of 2.98 ± 0.04 μg/mL and 5.71 ± 0.14 μg/mL, respectively. Flow-cytometry analysis was used to determine the cell cycle distribution and showed that the inhibition in NO release was accompanied by a reversion of the differentiation processes. Moreover, the anti-cancer potential of these 13 compounds were evaluated in three tumor cell lines (B16-F10, HT29, and Hep G2). The strongest cytotoxic effect was achieved by salicylaldehyde 20, and pterolobirin G (6), with IC50 values around 3 μg/mL in HT29 cells, with total apoptosis rates 80% at IC80 concentrations, producing a significant cell-cycle arrest in the G0/G1 phase, and a possible activation of the extrinsic apoptotic pathway. Additionally, initial SAR data analysis showed that the methyl group at the C-14 positions of cassane diterpenoids is not always important for their cytotoxic and anti-inflammatory activities.
Taiwaniaquinoids are a unique family of diterpenoids predominantly isolated from Taiwania cryptomerioides Hayata. Previously, we evaluated the antiproliferative effect of several synthetic ...taiwaniaquinoids against human lung (A-549), colon (T-84), and breast (MCF-7) tumor cell lines. Herein, we report the in vitro and in vivo antitumor activity of the most potent compounds. Their cytotoxic activity against healthy peripheral blood mononuclear cells (PBMCs) has also been examined. We underscore the limited toxicity of compound C36 in PBMCs and demonstrate that it exerts its antitumor effect in MCF-7 cells (IC50 = 1.8 µM) by triggering an increase in reactive oxygen species, increasing the cell population in the sub-G1 phase of the cell cycle (90 %), and ultimately activating apoptotic (49.6 %) rather than autophagic processes. Western blot results suggested that the underlying mechanism of the C36 apoptotic effects was linked to caspase 9 activation and a rise in the Bax/Bcl-2 ratio. In vivo analyses showed normal behavior and hematological parameters in C57BL/6 mice post C36 treatment. Moreover, no significant impact was observed on the biochemical parameters of these animals, indicating that C36 did not induce liver toxicity. Furthermore, C36 demonstrated a significant reduction in tumor growth in immune-competent C57BL/6 mice implanted with E0771 mouse mammary tumor cells, effectively improving survival rates. These findings position taiwaniaquinoids, particularly compound C36, as promising therapeutic candidates for human breast cancer.
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•Synthesized taiwaniaquinoids display potent cytotoxicity against cancer cells.•C36 exhibits low toxicity in normal cells, suggesting therapeutic potential.•C36 acts by generating ROS, halting the cell cycle and inducing apoptosis.•In vivo studies confirm the safety and anticancer efficacy of C36.
The acid treatment of 6,7-seco-abietane dialdehydes gives, in high yield, the corresponding derivatives with the 4a-methyltetrahydrofluorene skeleton of taiwaniaquinoids. A mechanism involving the ...elimination of formic acid from the cyclic aldol intermediate is proposed here. This process can be postulated as a new biogenetic pathway from abietane diterpenes to taiwaniaquinoids. Using this novel reaction, the first enantiospecific synthesis of bioactive natural cupresol and taxodal has been obtained.
Synthesis of the rearranged abietane diterpenes pygmaeocins C and D, viridoquinone, saprorthoquinone, and 1-deoxyviroxocine has been successfully achieved. The anticancer and anti-inflammatory ...activities of selected orthoquinonic compounds 5, 7, 13, and 19, as well as pygmaeocin C (17), were evaluated for the first time. The antitumor properties were assessed using three cancer cell lines: HT29 colon cancer cells, Hep G2 hepatocellular carcinoma cells, and B16-F10 murine melanoma cells. Compounds 5 and 13 showed the highest cytotoxicity in HT29 cells (IC50 = 6.69 ± 1.2 µg/mL and IC50 = 2.7 ± 0.8 µg/mL, respectively). Cytometric studies showed that this growth inhibition involved phase S cell cycle arrest and apoptosis induction, possibly through the activation of the intrinsic apoptotic pathway. Morphological apoptotic changes, including nuclear fragmentation and chromatin condensation, were also observed. Furthermore, the anti-inflammatory activity of these compounds was evaluated on the basis of their ability to inhibit nitric oxide production on the lipopolysaccharide activated RAW 264.7 macrophage cell line. Although all compounds showed high anti-inflammatory activity, with percentages between 40 and 100%, the highest anti-inflammatory potential was obtained by pygmaeocin B (5) (IC50NO = 33.0 ± 0.8 ng/mL). Our results suggest that due to their dual roles, this type of compound could represent a new strategy, contributing to the development of novel anticancer agents.
Treatment of (−)-sclareol and related compounds with lead tetraacetate affords tetracyclic compounds bearing a 2,8-dioxabicyclo5.2.0nonane moiety with complete regio- and stereoselectivity. This ...process, which is also applicable to 1,5-diols with a similar substitution pattern, facilitates the development of efficient syntheses toward oxepane terpenoids, such as aplysistatin derivatives.
The objective of this pilot study was to gather and analyze data on radon concentrations in workplaces in three buildings of Granada University (Southern Spain) constructed in different centuries. ...All measurements were made at basement or ground floor level under normal use conditions except for one space (mineral store), in which measurements were compared between the door closed and open. Measurements were conducted during different time periods between October 2013 and March 2019 with a Radon-Scout PLUS portable Radonmonitor. The duration of continuous recordings at different sites ranged between 42 and 1104 h. Mean accumulated radon concentrations ranged between 12 and 95 Bq/m
, below the maximal level of 300 Bq/m
set by the World Health Organization (WHO). Relatively high values were recorded in the oldest building (15th century), which was also poorly ventilated. Ventilation appeared to be an important factor in reducing radon levels, especially in areas less exposed to radon, such as Southern Spain.
Two main products namely 18-hydroxy-
cis
-clerodan-3-ene-15-oic acid and 18-acetoxy-
cis
-clerodan-3-ene-15-oic acid were isolated from the extract of the plant
Cistus monspeliensis
. The 18-acetoxy ...acid converted to its mother 18-hydroxy acid in good yield. Other two 1,3,4- oxadiazole derivatives namely 5-((R)-4-((1S,2R,4aS,8aR)-5-(hydroxymethyl)-1,2,4a-trimethyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl)-2-methylbutyl)-1,3,4-oxadiazole-2(3H)-thione and 5-((R)-2-methyl-4-((1S,2R,4aS,8aR)-1,2,4a,5-tetramethyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl)butyl)-1,3,4-oxadiazole-2(3H)-thione were synthesized from the obtained acid, characterized by infrared,
1
H,
13
C-NMR and mass spectroscopy. Their antioxidant power using the DPPH method showed interesting results compared with the reference ascorbic acid (IC
50
= 16.30 μM). Their antibacterial activity on Gram-positive bacteria
Staphylococcus aureus
(ATCC 33862) and
Bacillus cereus
(ATCC 10876), and Gram-negative bacteria
Pseudomonas aeruginosa
(ATCC 27853) and
Escherichia coli
(ATCC 25922) showed that the resulting 1,3,4-oxadiazole thiones have interesting effects against both Gram-positive bacteria using amikacin as a positive reference. The anti-inflammatory activity investigation showed that both clerodane diterpenoid 1,3,4-oxadiazolyl-5-thionyl derivatives had higher inhibition effect on the nitric oxide production with IC
50 NO
values of 43.59 ± 1.8 and 18.64 ± 0.06 μM compared to that of diclofenac (IC
50 NO
= 73.30 ± 0.40 μM). Docking studies showed that the terpene skeleton of the starting material and both heterocycles form hydrophobic and H-bonds interactions with iNOS. The thione group of the C18-methyl oxadiazole forms a hydrogen bond with Met368, which may explain its highest anti-inflammatory activity.
Graphical abstract
Treatment of o-allyl phenols with catalytic NIS–PPh3 affords the corresponding spirodihydrobenzofuran derivatives in high yield with high regio- and total stereoselectivity under mild conditions. ...These results were utilized to achieve the first total synthesis of the protein kinase C inhibitor corallidictyal D starting from α-ionone.
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