Red Fluorescent Molecule with Aggregation-Induced Emission Based on Dehydroabietic Acid Diarylamine for Bioimaging.

In this paper, molecules with AIE red light properties were designed by coupling dehydroabietic acid diarylamine and 2,3-diphenylfumaronitrile, which were designated 2DTPA-CN and 2TPA-CN. The emission wavelengths were 683 nm and 701 nm, respectively. The 2DTPA-CN and 2TPA-CN showed typical AIE characteristics with large Stokes shifts of 7.4 × 104 cm-1 and 6.7 × 104 cm-1, respectively. The obvious solvatochromism and electron cloud distributions of HOMO/LUMO in the ground and excited states both reveal the intramolecular charge transfer (ICT) effect. The 2DTPA-CN, boasting exceptional biocompatibility, was successfully prepared into nanoparticles (NPs), which were applied to tumor cell imaging, showing good bioimaging effects both in vitro imaging in live cells and in vivo imaging in live mice. The results demonstrated that it possesses significant potential as an effective bioimaging reagent for the detection of tumor cells. Furthermore, the incorporation of 2,3-diphenylfumaronitrile moieties to dehydroabietic acid diarylamine emerged as a proficient approach to broaden the emission wavelengths of rosin-based fluorescent materials.

Synthesis, antitumor evaluation and computational study of thiazolidinone derivatives of dehydroabietic acid-based B ring-fused-thiazole.

In an attempt to search for new natural product-based antitumor agents, a series of novel thiazolidinone derivatives of dehydroabietic acid-based B ring-fused-thiazole were designed and synthesized. The primary antitumor tests showed that compounds 5 m exhibited almost the best inhibitory activity against the tested cancer cells. The computational study suggested NOTCH1, IGF1R, TLR4, and KDR were the core targets of the title compounds, and the IC50 of SCC9 and Cal27 is strong correlation with the binding ability of TLR4 and compounds.

CYP72D19 from Tripterygium wilfordii catalyzes C-2 hydroxylation of abietane-type diterpenoids.

KEY MESSAGE: CYP72D19, the first functional gene of the CYP72D subfamily, catalyzes the C-2 hydroxylation of abietane-type diterpenoids. The abietane-type diterpenoids, e.g., triptolide, tripdiolide, and 2-epitripdiolide, are the main natural products for the anti-tumor, anti-inflammatory, and immunosuppressive activities of Tripterygium wilfordii, while their biosynthetic pathways are not resolved. Here, we cloned and characterized the CYP72D19-catalyzed C-2 hydroxylation of dehydroabietic acid, a compound that has been proven to be a biosynthetic intermediate in triptolide biosynthesis. Through molecular docking and site-directed mutagenesis, L386, L387, and I493 near the active pocket were found to have an important effect on the enzyme activity, which also indicates that steric hindrance of residues plays an important role in function. In addition, CYP72D19 also catalyzed a variety of abietane-type diterpenoids with benzene ring, presumably because the benzene ring of the substrate molecule stabilized the C-ring, allowing the protein and the substrate to form a relatively stable spatial structure. This is the first demonstration of CYP72D subfamily gene function. Our research provides important genetic elements for the structural modification of active ingredients and the heterologous production of other 2-hydroxyl abietane-type natural products.

Anti-Virulence Strategy of Novel Dehydroabietic Acid Derivatives: Design, Synthesis, and Antibacterial Evaluation.

Anti-virulence strategies are attractive and interesting strategies for controlling bacterial diseases because virulence factors are fundamental to the infection process of numerous serious phytopathogenics. To extend the novel anti-virulence agents, a series of dehydroabietic acid (DAA) derivatives decorated with amino alcohol unit were semi-synthesized based on structural modification of the renewable natural DAA and evaluated for their antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac), and Pseudomonas syringae pv. actinidiae (Psa). Compound 2b showed the most promising antibacterial activity against Xoo with an EC50 of 2.7 µg mL-1. Furthermore, compound 2b demonstrated remarkable control effectiveness against bacterial leaf blight (BLB) in rice, with values of 48.6% and 61.4% for curative and protective activities. In addition, antibacterial behavior suggested that compound 2b could suppress various virulence factors, including EPS, biofilm, swimming motility, and flagella. Therefore, the current study provided promising lead compounds for novel bactericides discovery by inhibiting bacterial virulence factors.

Design and Properties of Natural Rosin-Based Phosphoester Functional Surfactants.

As an important forestry biomass resource, rosin has a wide range of applications in medicine, adhesives, surfactants and other fields. Using natural dehydroabietic acid as a raw material, dehydroabietic acid-based phosphorus monoester (DPM) and diester (DPD) surfactants were designed and synthesized. The chemical structures and self-assembly properties were characterized by FT-IR, NMR and TEM, and the effects of pH on critical micelle concentration, γCMC, emulsifying properties, foam properties and micelle morphology were studied. The results showed that the CMC, γCMC value and aggregate morphology had certain pH responsiveness. The γCMC value under acidic conditions was smaller than γCMC under alkaline conditions, and the foaming performance and foam stability under acidic conditions were better than those under alkaline conditions. TEM micelle morphology studies have shown that DPM and DPD surfactants can self-assemble into rod-shaped and spherical micelle morphologies with a pH change in an aqueous solution. At the same pH, the foaming and emulsification properties of DPD were better than those of DPM. The best foaming and emulsification ability of DPD were 11.8 mL and 175 s, respectively. At the same time, the foaming ability of DPD is also affected by pH. DPD has excellent foaming properties in acidic conditions, but these disappeared in neutral conditions.

Design, synthesis and biological evaluation of dehydroabietic acid derivative as potent vasodilatory agents.

Using dehydroabietic acid as the lead compound for structural modification, 25 dehydroabietic acid derivatives were synthesized. Among them, compound D1 not only showed the strongest relaxation effect on the aortic vascular ring in vitro (Emax = 99.5 ± 2.1%, EC50 = 3.03 ± 0.96 µM), but also significantly reduced systolic and diastolic blood pressure in rats at a dose of 2.0 mg/kg in vivo. Next, the vascular protective effect of the best active D1 and its molecular mechanism were further investigated by HUVECs. The results showed that D1 induced endothelium-dependent diastole in the rat thoracic aorta in a concentration-dependent manner. Endothelium removal or aortic ring pretreatment with NG-nitro-l-arginine methylester (l-NAME), 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one (ODQ), and tetraethylammonium (TEA) significantly inhibited D1-induced relaxation. In addition, wortmannin, KT5823, triciribine, diltiazem, BaCl2, 4-aminopyridine, indomethacin, propranolol, and atropine attenuated D1-induced vasorelaxation. D1 increased the phosphorylation of eNOS in HUVECs Furthermore, D1 attenuated the expression of TNF-α-induced cell adhesion molecules such as ICAM-1 and VCAM-1. However, this effect was attenuated by the eNOS inhibitors l-NAME and asymmetric dimethylarginine (ADMA). The findings suggest that D1-induced vasorelaxation through the PI3K/Akt/eNOS/NO/cGMP/PKG pathway by activating the KCa, Kir and KV channels or muscarinic and ß-adrenergic receptors, and inhibiting the l-type Ca2+ channels, which is closely related to the hypotensive action of the agent. Furthermore, D1 exhibits an inhibitory effect on vascular inflammation, which is associated with the observed vascular protective effects.

Experimental Determination and Computational Prediction of Dehydroabietic Acid Solubility in (-)-α-Pinene + (-)-ß-Caryophyllene + P-Cymene System.

The solubility of dehydroabietic acid in (-)-α-pinene, p-cymene, (-)-ß-caryophyllene, (-)-α-pinene + p-cymene, (-)-ß-caryophyllene + p-cymene and (-)-α-pinene + (-)-ß-caryophyllene were determined using the laser monitoring method at atmospheric pressure. The solubility of dehydroabietic acid was positively correlated with temperature from 295.15 to 339.46 K. (-)-α-pinene, p-cymene, and (-)-ß-caryophyllene were found to be suitable for the solubilization of dehydroabietic acid. In addition, the non-random two liquid (NRTL), universal quasi-chemical (UNIQUAC), modified Apelblat, modified Wilson, modified Wilson-van't Hoff, and λh models were applied to correlate the determined solubility data. The modified Apelblat model gave the minor deviation for dehydroabietic acid in monosolvents, while the λh equation showed the best result in the binary solvents. A comparative analysis of compatibility between solutes and solvents was carried out using Hansen solubility parameters. The thermodynamic functions of ΔsolH0, ΔsolS0, ΔsolG0 were calculated according to the van't Hoff equation, indicating that the dissolution was an entropy-driven heat absorption process. The Conductor-like Screening Model for Real Solvents (COSMO-RS) combined with an experimental value was applied to predict the reasonable solubility data of dehydroabietic acid in the selected solvents systems. The interaction energy of the dehydroabietic acid with the solvent was analyzed by COSMO-RS.

Semisynthetic Abietic and Dehydroabietic Acid Derivatives and Triptoquinone Epimers Interfere with LPS-Triggered Activation of Dendritic Cells.

Abietic acid (AA), dehydroabietic acid (DHA) and triptoquinones (TQs) are bioactive abietane-type diterpenoids, which are present in many edible vegetables and medicinal herbs with health-promoting properties. Evidence suggests that beneficial effects of diterpenes operate, at least in part, through effects on cells in the immune system. Dendritic cells (DCs) are a key type of leukocyte involved in the initiation and regulation of the immune/inflammatory response and natural or synthetic compounds that modulate DC functions could be potential anti-inflammatory/immunomodulatory agents. Herein, we report the screening of 23 known semisynthetic AA and DHA derivatives, and TQs, synthesized previously by us, in a multi-analyte DC-based assay that detects inhibition of pro-inflammatory cytokine production. Based on the magnitude of the inhibitory effect observed and the number of cytokines inhibited, a variety of activities among compounds were observed, ranging from inactive/weak to very potent inhibitors. Structurally, either alcohol or methyl ester substituents on ring A along with the introduction of aromaticity and oxidation in ring C in the abietane skeleton were found in compounds with higher inhibitory properties. Two DHA derivatives and two TQs exhibited a significant inhibition in all pro-inflammatory cytokines tested and were further investigated. The results confirmed their ability to inhibit, dose dependently, LPS-stimulated expression of the co-stimulatory molecules CD40 and/or CD86 and the production of the pro-inflammatory cytokines IL-1ß, IL-6, IL-12 and TNFα. Our results demonstrate that DC maturation process can be targeted by semisynthetic DHA derivatives and TQ epimers and indicate the potential of these compounds as optimizable anti-inflammatory/immunomodulatory agents.

Synthesis and Antiproliferative Activity of Novel Dehydroabietic Acid-Chalcone Hybrids.

Dehydroabietic Acid (DHA, 1) derivatives are known for their antiproliferative properties, among others. In the context of this work, DHA was initially modified to two key intermediates bearing a C18 methyl ester, a phenol moiety at C12, and an acetyl or formyl group at C13 position. These derivatives allowed us to synthesize a series of DHA-chalcone hybrids, suitable for structure-activity relationship studies (SARS), following their condensation with a variety of aryl-aldehydes and methyl ketones. The antiproliferative evaluation of the synthesized DHA-chalcone hybrids against three breast cancer cell lines (the estrogen-dependent MCF-7 and the estrogen-independent MDA-MB-231 and Hs578T) showed that eight derivatives (33, 35, 37, 38, 39, 41, 43, 44) exhibit low micromolar activity levels (IC50 2.21-11.5 µΜ/MCF-7). For instance, some of them showed better activity compared to the commercial anticancer drug 5-FU against MCF-7 cells (33, 41, 43, 44) and against MDA-MB231 (33 and 41). Hybrid 38 is a promising lead compound for the treatment of MCF-7 breast cancer, exhibiting comparable activity to 5-FU and being 12.9 times less toxic (SI = 22.7). Thus, our findings suggest that DHA-chalcone hybrids are drug candidates worth pursuing for further development in the search for novel breast cancer therapies.

Screening of pyroptosis-related genes influencing the therapeutic effect of dehydroabietic acid in liver cancer and construction of a survival nomogram.

OBJECTIVE: This study aimed to screen pyroptosis-related genes influencing the therapeutic effect of dehydroabietic acid in liver cancer and to construct an effective survival prognostic nomogram model. METHODS: Differentially expressed genes (DEGs) between liver cancer tissues and normal tissues were analyzed with The Cancer Genome Atlas database, weighted gene coexpression network analysis and a genetic expression compilation database. The targets of dehydroabietic acid were screened with databases such as TCMSP and pharmacy. Spearman correlation analysis was analyzed. The prognosis model was built through one-factor Cox analysis and LASSO regression. The final core targets were screened by prognosis-related genes combined with a protein-protein interaction (PPI) network. On this basis, the survival nomogram was constructed. The effects of different concentrations of dehydroabietic acid on the growth of HepG2 liver cancer cells were detected by CCK8. Moreover, the expression of related genes was further verified through real-time fluorescence quantitative PCR and Western blot. RESULTS: Venn diagram analysis of DEGs of liver cancer in three databases was performed, through which 890 genes related to the genesis and development of liver cancer were acquired. According to Venn diagram analysis of targets of dehydroabietic acid and related genes of liver cancer, 44 intersecting targets for liver cancer treatment with dehydroabietic acid were acquired. Then, 7 prognosis-related genes were identified through one-factor Cox analysis and LASSO regression of 25 related genes. Next, 10 targets were screened through the PPI network, and the intersection was processed, thus obtaining 3 ultimate core targets of KIF11, CCNA2 and CDC25A. The IC50 of dehydroabietic acid is 23.22 ± 0.98 µg/mL. According to further verification of related genes, the mRNA and protein levels of KIF11, CCNA2 and CDC25A decrease significantly after treatment with dehydroabietic acid. The nomogram shows that T stage is an independent risk factor, and the postoperative survival C-index of the model group was 0.709. CONCLUSIONS: Three pyroptosis-related genes that influence the therapeutic effect of dehydroabietic acid in liver cancer were screened through bioinformatics methods. The survival prognostic nomogram model, which is built based on independent risk factors that influence the postoperative survival of patients in the T stage, has good accuracy and can provide references for clinical and fundamental studies in the future.

Synthesis and antitumor evaluation of (aryl)methyl-amine derivatives of dehydroabietic acid-based B ring-fused-thiazole as potential PI3K/AKT/mTOR signaling pathway inhibitors.

In an attempt to search for new natural product-based antitumor agents, a series of novel (aryl)methyl-amine derivatives of dehydroabietic acid-based B ring-fused-thiazole were designed and synthesized. The primary bioassay showed that compounds 5r and 5s presented certain inhibitory activity against cancer cells, weak cytotoxic activity against normal cells, and inhibitory activity against PI3K/AKT/mTOR signaling pathway. The binding modes and the binding site interactions between the active compounds and the target proteins were predicted preliminarily by the molecular docking method.

Facile Construction of Bio-Based Supramolecular Hydrogels from Dehydroabietic Acid with a Tricyclic Hydrophenanthrene Skeleton and Stabilized Gel Emulsions.

Supramolecular hydrogels have attracted great attention due to their special properties. In this research, bio-based supramolecular hydrogels were conveniently constructed by heating and ultrasounding two components of dehydroabietic acid with a rigid tricyclic hydrophenanthrene skeleton and morpholine. The microstructures and properties of hydrogels were investigated by DSC, rheology, SAXS, CD spectroscopy, and cryo-TEM, respectively. The critical gel concentration (CGC) of the hydrogel was 0.3 mol·L-1 and the gel temperature was 115 °C. In addition, the hydrogel showed good stability and mechanical properties according to rheology results. Cryo-TEM images reveal that the microstructure of hydrogel is fibrous meshes; its corresponding mechanism has been studied using FT-IR spectra. Additionally, oil-in-water gel emulsions were prepared by the hydrogel at a concentration above its CGC, and the oil mass fraction of the oil-in-water gel emulsions could be freely adjusted between 5% and 70%. This work provides a convenient way to prepare bio-based supramolecular hydrogels and provides a new method for the application of rosin.

Synthesis and anticancer evaluation of novel 1H-benzo[d]imidazole derivatives of dehydroabietic acid as PI3Kα inhibitors.

Phosphatidylinositol 3-kinase (PI3K) is one of the most attractive therapeutic targets for cancer treatment. In this study, a series of new 2-arylthio- and 2-arylamino-1H-benzo[d]imidazole derivatives of dehydroabietic acid were designed, synthesized and characterized by 1H NMR, 13C NMR, IR and MS spectra analyses. In the in vitro anticancer assay, some title compounds showed significant inhibitory activities against four cancer cell lines (HCT-116, MCF-7, HeLa and HepG2). Among them, compound 9g exhibited the most potent activity with IC50 values of 0.18 ± 0.03, 0.43 ± 0.05, 0.71 ± 0.08 and 0.63 ± 0.09 µM against four cancer cell lines, and considerably lower cytotoxicity to human gastric mucosal cell line Ges-1 (IC50: 21.95 ± 0.73 µM). Besides, compound 9g displayed a certain selective activity to PI3Kα (IC50 = 0.012 ± 0.002 µM) over PI3Kß, γ and δ, and meanwhile, it can remarkably decrease the expression level of p-Akt (Ser473). In addition, compound 9g could increase intracellular reactive oxygen species level, decrease mitochondrial membrane potential, upregulate Bax and cleaved caspase-3/9 levels, downregulate Bcl-2 level and thus induce the apoptosis of HCT-116 cells in a dose-dependent manner. The results suggested that compound 9g could be considered as a promising PI3Kα inhibitor.

Widely Adaptable Oil-in-Water Gel Emulsions Stabilized by an Amphiphilic Hydrogelator Derived from Dehydroabietic Acid.

A surfactant, R-6-AO, derived from dehydroabietic acid has been synthesized. It behaves as a highly efficient low-molecular-weight hydrogelator with an extremely low critical gelation concentration (CGC) of 0.18 wt % (4 mm). R-6-AO not only stabilizes oil-in-water (O/W) emulsions at concentrations above its critical micelle concentration (cmc) of 0.6 mm, but also forms gel emulsions at concentrations beyond the CGC with the oil volume fraction freely adjustable between 2 % and 95 %. Cryo-TEM images reveal that R-6-AO molecules self-assemble into left-handed helical fibers with cross-sectional diameters of about 10 nm in pure water, which can be turned to very stable hydrogels at concentrations above the CGC. The gel emulsions stabilized by R-6-AO can be prepared with different oils (n-dodecane, n-decane, n-octane, soybean oil, olive oil, tricaprylin) owing to the tricyclic diterpene hydrophobic structure in their molecules that enables them to adopt a unique arrangement in the fibers.

Synthesis and biological evaluation of novel N-(piperazin-1-yl)alkyl-1H-dibenzo[a,c]carbazole derivatives of dehydroabietic acid as potential MEK inhibitors.

In this paper, a series of novel 1H-dibenzo[a,c]carbazole derivatives of dehydroabietic acid bearing different N-(piperazin-1-yl)alkyl side chains were designed, synthesised and evaluated for their in vitro anticancer activities against three human hepatocarcinoma cell lines (SMMC-7721, HepG2 and Hep3B). Among them, compound 10g exhibited the most potent activity against three cancer cell lines with IC50 values of 1.39 ± 0.13, 0.51 ± 0.09 and 0.73 ± 0.08 µM, respectively. In the kinase inhibition assay, compound 10g could significantly inhibit MEK1 kinase activity with IC50 of 0.11 ± 0.02 µM, which was confirmed by western blot analysis and molecular docking study. In addition, compound 10g could elevate the intracellular ROS levels, decrease mitochondrial membrane potential, destroy the cell membrane integrity, and finally lead to the oncosis and apoptosis of HepG2 cells. Therefore, compound 10g could be a potent MEK inhibitor and a promising anticancer agent worthy of further investigations.

Dehydroabietic Acid Induces Regeneration of Collagen Fibers in Ultraviolet B-Irradiated Human Dermal Fibroblasts and Skin Equivalents.

BACKGROUND/AIMS: Dehydroabietic acid (DAA) is a natural phytochemical found in red pine trees and herbal plants. While DAA and its derivatives are known for improving diabetes and hyperlipidemia, the antiaging effect and its underlying mechanisms of DAA on skin have not been fully examined. Here, we assessed the antiaging effects of DAA on human dermal fibroblasts and skin equivalents. METHODS: We investigated the effect of DAA on the secretion of type I procollagen and matrix metalloproteinase-1 (MMP-1) in ultraviolet B (UVB)-irradiated neonatal normal human dermal fibroblasts (NHDFn). Using nonlinear optical imaging techniques, we visualized quantitative and qualitative changes of collagen fibers by DAA treatment in human skin equivalent models. RESULTS: DAA induces increases in type I procollagen secretion when treated on UVB-irradiated NHDFn. DAA also downregulates secretion of MMP-1 through the inhibition of the JNK signaling pathway. In human skin equivalent models, we successfully visualized the spatial distribution of collagen fibers in the dermis and found that quantity, diameter, and arrangement of collagen fibers in the dermis were significantly improved by DAA treatment. CONCLUSION: Our results suggest that DAA could be a useful agent for improving skin photoaging through the protection and regeneration of collagen fibers in skin.

Identification and Quantitative Determination of Resin Acids from Corsican Pinus pinaster Aiton Oleoresin Using 13 C-NMR Spectroscopy.

Twenty-three resin samples have been obtained by tapping from individual Pinus pinaster adult trees grown in Corsica and submitted to acido-basic partition. Identification and quantitative determination of resin acids has been carried out using 13 C-NMR spectroscopy following a method developed by our group. The main components were dehydroabietic acid (up to 37.6 %), levopimaric acid (up to 35.5 %) and abietic acid (up to 24.7 %). A lignan, pinoresinol, has been identified in some samples. Within the 23 compositions, submitted to k-means analysis and Principal Component Analysis, two clusters have been perfectly differentiated, whose compositions were dominated by dehydroabietic acid (Group I, M=23.5 %, SD=6.3) and levopimaric acid (Group II, M=21.2 %; SD=6.2), respectively. Both compositions have been observed in the three locations of harvest.

Dehydroabietic Acid Suppresses Inflammatory Response Via Suppression of Src-, Syk-, and TAK1-Mediated Pathways.

Dehydroabietic acid (DAA) is a naturally occurring diterpene resin acid derived from coniferous plants such as Pinus and Picea. Various bioactive effects of DAA have been studied including antibacterial, antifungal, and anticancer activities. However, the anti-inflammatory mechanism of DAA remains unclear. We evaluated the anti-inflammatory effect of DAA in macrophage cell lines. Dehydroabietic acid clearly reduced nitric oxide (NO) production and inflammatory gene expression decreased according to RT-PCR results. Dehydroabietic acid displayed anti-inflammatory activity at the transcriptional level in results from NF-κB- or AP-1-mediated luciferase assays. To identify the DAA target protein, we investigated NF-κB and AP-1 pathways by Western blotting analysis. Dehydroabietic acid suppressed the activity of proto-oncogene tyrosine protein kinase (Src) and spleen tyrosine kinase (Syk) in the NF-κB cascade and transforming growth factor beta-activated kinase 1 (TAK1) in the AP-1 cascade. Using overexpression strategies, we confirmed that DAA targeted these kinases. Our findings demonstrate the anti-inflammatory effects and molecular mechanism of DAA. This suggests that DAA has potential as a drug or supplement to ameliorate inflammation.

Synthesis and Antiproliferative Evaluation of Novel Hybrids of Dehydroabietic Acid Bearing 1,2,3-Triazole Moiety.

To discover novel potent cytotoxic diterpenoids, a series of hybrids of dehydroabietic acid containing 1,2,3-triazole moiety were designed and synthesized. The target compounds were characterized by means of FT-IR, 1H NMR, 13C NMR, ESI-MS and elemental analysis techniques. The in vitro cytotoxicity of these compounds was evaluated by standard MTT (methyl thiazolytetrazolium) assay against CNE-2 (nasopharynx), HepG2 (liver), HeLa (epithelial cervical), BEL-7402 (liver) human carcinoma cell lines and human normal liver cell (HL-7702). The screening results revealed that most of the hybrids showed significantly improved cytotoxicity over parent compound DHAA. Among them, [1-(3-fluorobenzyl)-1H-1,2,3-triazole-4-yl]dehydroabietic acid methyl ester (3c), and [1-(2-nitrobenzyl)-1H-1,2,3-triazole-4-yl]dehydroabietic acid methyl ester (3k) displayed better antiproliferative activity with IC50 (50% inhibitory concentration) values of 5.90 ± 0.41 and 6.25 ± 0.37 µM toward HepG2 cells compared to cisplatin, while they exhibited lower cytotoxicity against HL-7702. Therefore, the 1,2,3-triazole-hybrids could be a promising strategy for the synthesis of antitumor diterpenoids and it also proved the essential role of 1,2,3-triazole moiety of DHAA in the biological activity.

The synthesis and antistaphylococcal activity of N-sulfonaminoethyloxime derivatives of dehydroabietic acid.

A series of N-sulfonaminoethyloxime derivatives of dehydroabietic acid were synthesized and investigated for their antibacterial activity against Staphylococcus aureus Newman strain and multidrug-resistant strains (NRS-1, NRS-70, NRS-100, NRS-108 and NRS-271). Most of the target compounds having chloro, bromo, trifluoromethyl phenyl moiety exhibited potent in vitro antistaphylococcal activity. The meta-CF3 phenyl derivative T23 showed the highest activity with MIC of 0.39-0.78 µg/mL against S. aureus Newman, while several analogues showed similar potent antibacterial activity with MIC values between 0.78 and 1.56 µg/mL against five multidrug-resistant S. aureus. The stability of T35 in plasma of SD rat and the cellular cytotoxicity were also evaluated.