Enhancing Systemic Translocation of Insecticides via Nanoformulations Incorporating ß-Cyclodextrin Octadecarboxylate as a Carrier.

The conversion of contact-killing pesticides into systemic pesticides can significantly enhance the bioavailability of pesticides, thereby reducing pesticide usage and environmental harm. A series of ß-cyclodextrin fatty acid esters with varying branch chains were synthesized and employed as carriers in nanoformulation of insecticide. The investigation revealed that nanoformulations prepared using ß-cyclodextrin octadecarboxylate (ß-CDs) exhibited superior stability and remarkable systemic translocation within plants. Six contact-killing insecticide nanoformulations were developed utilizing ß-CDs as carriers, and tests indicated that ß-CDs significantly enhanced the systemic translocation of insecticides in plants compared to carrier-free nanoformulations. It was found that ß-CDs increased the level of systemic translocation of insecticides by 5-12 times. Additionally, characterization results from λ-cyhalothrin-ß-CDs nanoformulation demonstrated their superior ability to improve photolysis resistance, prolong release time, and extend insecticidal duration. Consequently, ß-CDs can be utilized as a green additive in pesticide production to enhance the systemic translocation of pesticides in plants and increase their bioavailability.

Synthesis, antitumor activity evaluation of 2-selenocyano-3-selenocyanoalkyloxyestradiols with a bisselenocyanate structure.

The combination of steroid structure and selenocyano group offers high potential for the design and synthesis of new potential anti-tumor drugs. Beginning with estradiol, a series of 2-selenocyano-3-selenocyanoalkyloxyestradiol derivatives with remarkable antiproliferative activity was synthesized. Additionally, a 2,4-bisselenocyanoestradiol was synthesized by directly selenocyanating estradiol diacetate. It was found that the cytotoxicity of 2-selenocyano-3-selenocyanoalkyloxyestradiol derivatives was significantly increased in comparison to the corresponding monoselenocyanate precursor, whereas the cytotoxicity of the 2, 4-bisselenocyanoestradiol derivative was significantly reduced compared to the respective monosubstituted precursor. The introduction of the second selenocyano group at different locations of estradiol shows a various impact on the cytotoxicity of the compounds. Among them, compound 3e showed the best cytotoxicity, with an IC50 value of less than 5 µM against the tested tumor cells, and strong inhibitory activities against HeLa and MCF-7 cell xenograft tumors in zebrafish, suppressing tumor cell migration and neovascularization. Notably, compound 3e was more effective at inhibiting neovascularization of MCF-7 cell xenograft tumors than the positive control 2-methoxyestradiol. Furthermore, compound 3e showed excellent anti-oxidative stress effect in zebrafish. Therefore, these estrogen bisselenocyanate compounds may be promising anti-tumor agents, warranting further investigation.

Emamectin-sodium alginate nano-formulation based on charge attraction with highly improved systemic translocation and photolysis resistance.

Nano pesticides offer an effective means of improving the bioavailability of pesticide due to their excellent solubility and wettability, superior foliar adhesion, and permeability to target insects. By using high-speed homogenization and ultrasonic dispersion technology, an emamectin-sodium alginate nano-formulation (EB@SA) with a particle size ranging from 30 to 50 nm was successfully fabricated using electrostatic self-assembly. The microscopic morphology and structure of EB@SA were further analyzed through transmission electron microscopy, dynamic light scattering, infrared spectroscopy, and 1H NMR. The photolysis resistance behavior of EB@SA demonstrated an improved anti-photolysis ability more than double that of conventional formulations while also exhibiting good sustained-release properties. Not only does EB@SA maintain the inherent insecticidal toxicity of emamectin benzoate (EB), but it also significantly prolongs its insecticidal duration. At a concentration of 20 mg/L, the lethality rate against Armyworms remains above 70 % over a period of 16 days compared to <50 % for general emamectin emulsifiable concentrate. Furthermore, EB@SA greatly enhances the systemic translocation of EB in corn plants by exhibiting favorable bidirectional systemic translocation characteristics. This research presents an efficient and environmentally friendly pesticide nano-formulation that can be effectively utilized for field pest control.

Discovery and biological evaluation of pregnenolone selenocyanoamides with potential anticancer and antimicrobial activities.

Starting with pregnenolone, a 20-carbonyl group was converted into an amino group through a series of chemical reactions. This amino group was further converted into selenocyanoalkylamide, leading to the synthesis of six pregnenolone selenocyanoalkylamide derivatives. These compounds were then screened for antitumor activity in vitro, yielding promising results. Compounds 4b-4f show higher inhibitory activity than the positive control abiraterone and 2-methoxyestradiol, with IC50 values lower than 10 µmol/L against breast, ovarian, and cervical cancer cell lines that closely related to human hormone expression levels. The Annexin V assay of compound 4f revealed that compounds inhibited tumor cell proliferation primarily through the induction of programmed apoptosis. The zebrafish test results indicated that compound 4d had significant inhibitory activity against MCF-7 cell xenografts in vivo. Moreover, the antibacterial test indicated that compounds 4a and 4d-4e had better inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) than the positive controls vancomycin and ampicillin. These results suggest that these compounds may hold promise as novel antitumor agents or antimicrobial agents for further study.

Asymmetric α-Allylation of N-Unprotected Amino Acid Esters with 1,3-Disubstituted Allyl Acetates Enabled by Chiral-Aldehyde/Palladium Catalysis.

A chiral aldehyde/palladium catalysis-enabled asymmetric α-allylation of NH2-unprotected amino acid esters with 1,3-disubstituted allyl acetates is described in this work. With the utilization of different chiral phosphine ligands, both the anti- and syn-selective allylation reactions are achieved enantioselectively. A series of α,α-disubstituted amino acid esters bearing two adjacent chiral centers are produced in moderate-to-excellent yields, diastereoselectivities, and enantioselectivities.

Normalized TSH strategy can improve the initial assessment of thyroid nodules.

BACKGROUND: Serum thyrotropin (TSH) has been recommended for the initial assessment of patients with thyroid nodules to exclude functional thyroid nodules (FTN). However, the sensitivity of TSH is very low. The increased level of thyroid peroxidase antibody (TPOAb) is considered to be one of the reasons. OBJECTIVE: To investigate whether normalized TSH (nTSH) can improve diagnostic efficiency by removing TPOAb interference in the first evaluation of thyroid nodules compared with traditional TSH strategy. METHODS: Thyroid nodules were retrospectively analysed in 90 patients with FTN and 1038 patients with non-functioning thyroid nodules (non-FTN). The regression coefficient (ß) of TPOAb affecting the TSH levels was assessed in patients with thyroid nodules, and then, the nTSH level was calculated based on the following formula: nTSH = TSH-ß*TPOAb. We used nTSH levels to initially evaluate the thyroid nodules instead of the traditional TSH values and finally compared the results of the two strategies. RESULTS: The sensitivity, specificity, accuracy, positive prediction rate (PPV) and negative prediction rate (NPV) of nTSH for accessing FTN were 50.00%, 87.70%, 84.67%, 26.01% and 95.29%, respectively, which were better than the values of 48.90%, 78.70%, 76.33%, 16.60% and 94.67% associated with TSH, respectively (p < 0.001). CONCLUSION: Serum TPOAb testing is recommended for the first assessment of thyroid nodules. Normalized TSH levels can improve assessment efficiency compared to traditional TSH assessment, increase the specificity and reduce an unnecessary 99mTc-TS test.

Synthesis, characterization and application of emamectin-alkaline lignin conjugate with photolysis resistance and systemic translocation.

Controlled release formulations (CRFs) are a key technical approach for the sustainable development of pesticides. In this study, a CRF conjugate (emamectin-alkaline lignin, EB-AL) was successfully prepared using alkaline lignin as the substrate, with amide bond connecting emamectin and alkaline lignin. The structure and morphology of the conjugate were characterized using IR, 1HNMR, elemental analysis, SEM and TG. The release of EB-AL showed that the conjugate maintained its original structure when released in 50 % methanol-water and soil column, and the amide bond remained intact. The anti-photolysis test revealed that EB-AL had a 3.5 times higher photolysis half-life T0.5 than the general emamectin suspension concentrate (EB-SC). Bioactivity tests in the greenhouse demonstrated that EB-AL possessed a longer insecticidal duration and good biosafety. Ostrinia nubilalis lethality rate remained above 70 % for 19 days, while EB-EC, the control, had a rate of <50 % after 11 days of application. Additionally, EB-AL conjugate demonstrated excellent systemic translocation in plants, likely due to its ability to mediate alkaline lignin.

Synthesis and antitumor activity of some cholesterol-based selenocyanate compounds.

The introduction of selenium-containing functional groups into steroids to study the biological activities of related derivatives is rarely reported in the literature. In the present study, using cholesterol as raw material, four cholesterol-3-selenocyanoates and eight B-norcholesterol selenocyanate derivatives were synthesized, respectively. The structures of the compounds were characterized by NMR and MS. The results of the in vitro antiproliferative activity test showed that the cholesterol-3-selenocyanoate derivatives did not exhibit obvious inhibitory on the tested tumor cell lines. However, the B-norcholesterol selenocyanate derivatives obtained by structural modification of cholesterol showed good inhibitory activity against the proliferation of tumor cell. Among them, compounds 9b-c, 9f and 12 showed similar inhibitory activity against tested tumor cells as positive control 2-methoxyestradiol, and better than Abiraterone. At the same time, these B-norcholesterol selenocyanate derivatives displayed a strong selective inhibitory against Sk-Ov-3 cell line. Except for compound 9g, the IC50 value of all B-norcholesterol selenocyanate compounds against Sk-Ov-3 cells was less than 10 µM, and compound 9d was 3.4 µM. In addition, Annexin V-FITC/PI double staining was used to analyze the cell death mechanism. The results showed that compound 9c could induce Sk-Ov-3 cells to enter programmed apoptosis in a dose-dependent manner. Furthermore, the in vivo antitumor experiments of compound 9f against zebrafish xenograft tumor showed that 9f displayed obvious inhibitory effect on the growth of human cervical cancer (HeLa) xenograft tumor in zebrafish. Our results provide new thinking for the study of such compounds as new antitumor drugs.

Synthesis and Antiproliferative Activity Evaluation of B-norcholesterol-6- amide Compounds.

BACKGROUND: The structure modification of steroids is commonly used to change the biological activity of steroids in medicinal chemistry. In recent years, it has been found that some derivatives derived from the structural modification of cholesterol display good inhibitory activity against tumor cell proliferation in vitro. METHODS: Using cholesterol as the starting material, different types of B-norcholesterol-6-amide derivatives were synthesized by the reaction of 6-carboxyl-B-norcholesterol with different alkyl amines or 6-amino-B-norcholesterol with different acyl chlorides. The inhibitory activity of compounds on the proliferation of tumor cell lines was investigated by the MTT method. RESULTS: The results showed that the B-norcholesterol-6-amide compounds displayed distinct cytotoxicity against Sk-Ov-3 cells but caused no obvious damage against HEK-293T cells. Additionally, the steroidal amide derivatives formed from 6-amino-B-norcholesterol showed stronger cytotoxicity than those produced from 6-carboxyl-B-norcholesterol. Specially, compounds with chloroalkyl structure displayed significant inhibitory activity against all tumor cells tested. Among them, compounds 19-21 showed cytotoxicity like 2-methoxyestradiol as a positive control, and the IC₅₀ value of compound 20 on HeLa cells was 3.9 µM. CONCLUSION: After introducing chloroalkyl acyl groups into 6-position of 6-amino-B-norcholesterol, the cytotoxicity of resulting B-norcholesterol-6-amide compounds can be greatly enhanced.

Difluorocarbene-Triggered Acyl Rearrangement Reaction: A Strategy for the Direct Introduction of the gem-Difluoromethylene Group.

A novel metal- and catalyst-free dearomative reaction of 2-oxypyridines to construct gem-difluoromethylenated N-substituted 2-pyridones has been developed. The reaction involves an attractive acyl rearrangement from O to CF2 of difluorocarbene-derived pyridinium ylides, which provides a new strategy for the direct introduction of the gem-difluoromethylene group with high efficiency and selectivity as well as broad substrate scope. Gram-scale synthesis and synthetic transformations have also been demonstrated.

Straightforward synthesis of steroidal selenocyanates through oxidative umpolung selenocyanation of steroids and their antitumor activity.

Straightforward access to steroidal selenocyanates in a single assembly step from steroids remains a significant challenge. However, the development of novel method for the synthesis of steroidal selenocyanates and further investigation of their bioactivities have largely lagged behind. In this work, selenocyano groups were directly introduced into the 17- or 21-position of pregnenolone, the 2-position of estradiol, and the 16-position of estrone. A total of 16 estrogen selenocyanate derivatives with diverse structures were synthesized, and the tumor cell lines closely related to the expression level of estrogen were used to investigate the inhibitory activity of the target products on tumor cell proliferation in vitro. The results revealed that the 17-selenocyano-substituted pregnenolone selenocyanate derivatives 1b-3b exhibit obvious inhibitory activity against the tested tumor cell lines. Additionally, the 2-selenocyano-substituted estradiol derivatives and 16-selenocyano-substituted estrone derivatives exhibit selective inhibitory on HeLa cell lines. Among them, 2-selenocyano-3-methoxyestradiol-17-benzoate (7e) displayed an IC50 value of 4.1 µM against HeLa cells and induced programmed apoptosis in HeLa cancer cells. Furthermore, compound 7e could significantly inhibit the growth of human cervical cancer xenografts in zebrafish in vivo. This approach provides new insights for future steroid antitumor drug design.

Rh(III)-Catalyzed Synthesis of Amino-isocoumarins with N-Functionalized Cyclic Carbonates via C-H/O-H Annulation.

A practical method to access amino-isocoumarins catalyzed by a Rh(III) complex through redox-neutral C-H/O-H annulation has been disclosed. The use of N-functionalized cyclic carbonates is crucial to facilitate the catalytic turnover, and a broad spectrum of amino-isocoumarin derivatives were prepared with satisfactory yields. Amino-isocoumarin estrone conjugated with a selenocyano functionality was identified to be nearly four times as active as the marketed drug abiraterone against T47D cancer cells.

Synthesis of estrone selenocyanate Compounds, anti-tumor activity evaluation and Structure-activity relationship analysis.

Introducing different functional groups into steroid can bring unexpected changes in biological activity of the steroid. Using estrone as a raw material, through the functional group conversion and modification of the 17-carbonyl, the structural fragments with selenocyano groups were instilled in the form of amide, ester, and oxime ester, respectively, and various 17-substituted estrone selenocyanate derivatives were synthesized. In addition, different 3-substituted estrone selenocyanate derivatives were synthesized by introducing different selenocyanoalkoxy fragments into the 3-position of estrone in the form of alkyl ether. Furthermore, the selenocyano-containing moieties were embedded into the 2-position of estrone by means of amide, affording diverse 2-selenocyanoamide-estrone derivatives. The antiproliferative activities of the target compounds were screened by selecting tumor cell lines related to the expression of human hormones. The results showed that the introduction of selenocyano group into estrone could endow estrone with significant biological activity of inhibiting the proliferation of tumor cells. Structure-activity relationship research showed that the cytotoxicity of 3-selenocyanoalkoxy-estrone was further increased with the extension of alkyl carbon-chain within 8 carbon chain lengths. In addition, the cytotoxicity of the products with selenocyano via the form of amide was stronger than that of ester or ether. Selenocyano moiety instilled at the 2-position of estrone in the form of amide was more cytotoxic than that of 17- or 3-position. Among them, compound 21a has better inhibitory activity on tested tumor cells than positive controls Abiraterone and 2-methoxyestradiol. Research showed that the compound 21c induced programmed apoptosis in Sk-Ov-3 cancer cells, and compound 17d inhibited significantly the growth of human cervical cancer zebrafish xenografts in vivo, offering useful insights into the synthesis of steroid antitumor drugs.

Synergistic Sc(III)/Au(I)-Catalyzed Dearomative Spiroannulation of 2-(Ethynyl)aryl Cyclopropanes with 2-Aryl Indoles.

The diastereoselective assembly of spiroindolenines via a synergistic scandium/gold-catalyzed dearomative spiroannulation is herein described. This protocol offers access to a wide variety of spiroindolenine derivatives in 86% average yield with moderate to excellent diastereoselectivities (up to 97:3 dr). The control experimental studies lend support to the bimetallic relay catalysis. Moreover, the scale-up reaction and synthetic transformations of spiroindolenine product further demonstrate its synthetic utility.

Improved glucose yield and concentration of sugarcane bagasse by the pretreatment with ternary deep eutectic solvents and recovery of the pretreated liquid.

In this study, a novel ternary deep eutectic solvents (DES) consisting of choline chloride/PEG/hydroxyethyl sulfonic acid (HSA) was developed to effectively improve glucose yield and concentration of sugarcane bagasse, and the conditions of the pretreatment were optimized by response surface method (RSM). Under the optimal conditions, the maximum glucose concentration (GC) could reach 12.39 g/L (HSA concentration 1.34 %, PEG400, 2.3 h, 150 °C), and the maximum glucose yield (GY) was 0.2497 g/g (HSA concentration 1.41 %, PEG400, 2.1 h, 150 °C). Hemicellulose was completely removed, and the maximum lignin removal rate was 86.89 %. After pretreatment, 95 % of the pretreated liquid can be recycled. Finally, the structural and morphological changes of bagasse before and after pretreatment were investigated by scanning electron microscopy (SEM), Fourier Transform infrared analyzer (FT-IR) and X-ray diffraction (XRD).

Identification of estrogen receptor down-regulators for endocrine resistant breast cancer.

Resistance to endocrine therapies remains an impediment for the treatment of estrogen receptor (ER) positive breast cancer. ER down regulator Fulvestrant has showed great activity to overcome the endocrine resistance. However, Fulvestrant has poor bioavailability due to the hydrophobicity. Identification of novel ER down regulator is still important. Compounds 172 and 183 are two steroidal compounds with androgen scaffold but significantly down regulated ER in multiple breast cancer cell lines. RT-PCR results indicated that both compounds did not affect ER gene expression. Proteasome inhibitor MG132 could attenuate ER down regulation effect of the compounds, suggesting that the ER down regulation was via ubiquitin-proteasomal pathway. Furthermore, compounds 172 and 183 could downregulate ER in endocrine resistant breast cancer cell model long term estrogen deprivation (LTED) MCF-7 cells. Hydrophobicity of compounds 172 and 183 were determined and showed improved solubility compared to Fulvestrant. All these results suggested that compounds 172 and 183 could be potential lead compounds for drug development for the treatment of endocrine resistance breast cancer.

Preparation and Insecticidal Activity Evaluation of Emamectin-Lignin Sulfonic Acid Conjugate with Antiphotolysis Property.

Controlled release formulations (CRFs) are considered an effective way to solve the low bioavailability of traditional pesticides. However, CRFs prepared by coating or encapsulation has the disadvantage of explosive release of the ingredients. Sustained-release pesticides prepared by coupling with a carrier can overcome this shortcoming. In the present study, an emamectin-lignin sulfonic acid conjugate (EB-SL), in which emamectin was connected via sulfonamide bonds with lignin, was prepared using sodium lignosulfonate as the carrier. The structure of the conjugate was characterized by IR, 1HNMR, and elemental analysis. The sustained-release results showed that EB-SL maintained its original structure when released in pure water and soil columns, and the sulfamide bond did not break. The photolysis test displayed that the photolysis half-life T 0.5 of EB-SL was increased by 1.5 times compared with the emamectin suspending concentrate (EB-SC). Bioactivity tests in the greenhouse showed that EB-SL not only had similar insecticidal toxicity to emamectin emulsion concentrate (EB-EC) against Ostrinia nubilalis but also displayed a longer duration. The lethality of EB-SL on O. nubilalis was maintained at more than 70% across 19 days, whereas EB-EC as the control was less than 50% after 11 days of application.

Study on the preparation of sustained-release thiamethoxam microspheres by blending microcrystalline wax with tapioca starch ester or dehydroabietic acid ester as the matrix.

The controlled release formulations (CRFs) are considered an effective way to solve damage to the environment caused by traditional pesticide formulations. To change the defects of traditional neonicotinoid formulations that dissolve quickly in soil, three types of thiamethoxam (TM) CRFs microspheres with content of 20% TM were prepared using microcrystalline wax (MK) as the matrix, laurate acid tapioca starch ester (MSK) and stearyl dehydroabietic acid ester (MDK) as the regulators of ingredient release. The release behavior of CRFs microspheres in water and soil showed that the microspheres had superior stability and different TM sustained-release periods, and TM release of the microspheres in soil was faster than that in water. The release rate is TM/MDK > TM/MSK > TM/MK. In water, the release of thiamethoxam technical was finished after 38 hours. However, for TM/MK, the release rate was 94% after 240 hours, and the release time was extended by 6 times. Meanwhile, TM/MDK has a particular pH-responsive release. Research shows that using microcrystalline wax as the matrix, by adding MSK or MDK to adjust the release of ingredients, pesticide CRFs microspheres with different release periods can be prepared to achieve the purpose of controlling the release of pesticides.

Synthesis and antiproliferative evaluation of some novel estradiol selenocyanates.

Selenocyano fragments with different structural characteristics have been successfully installed into the 3- and 17-position of estradiol through the etherification and esterification of its 3 or 17-hydroxyl group respectively. A total of 12 new estradiol selenocyanates were synthesized and their structures were characterized by NMR and HRMS. The tumor cell lines related to the expression of human hormones were selected as the screening objects, and the antiproliferative activity of the target compounds was further investigated. The results showed that the introduction of selenocyano group in estradiol could endue estradiol with the activity of inhibiting tumor cell proliferation, and 3-selenocyanoalkyl estradiol ethers had stronger cytotoxicity than their 17-selenocyanocarboxylates counterpart. Among them, IC50 value of compound 3e on HeLa cells was 5.69 µM. The information obtained from the studies may be useful for the design and development of novel chemotherapeutic drugs.

Fabrication and evaluation of slow-release lignin-based avermectin nano-delivery system with UV-shielding property.

Nanopesticide is one of the best pesticide formulation technologies to overcome the disadvantages of traditional pesticides, which has received great attention from the international community. Using high-speed emulsification and ultrasonic dispersion technology, an avermectin nano-delivery system (Av-NDs) with a particle size of 80-150 nm was prepared through embedding the pesticide molecule utilizing the cross-linking reaction between sodium lignosulfonate and p-phenylenediamine diazonium salt. The formulation and composition of Av-NDs were optimized, the morphology of Av-NDs was analyzed by scanning electron microscope, transmission electron microscope and dynamic light scattering, and the structure of Av-NDs was characterized by UV, IR and 1H NMR. Anti-photolysis and controlled-release tests show that the stability of Av-NDs is 3-4 times of the original avermectin (Av) and possesses the pH-responsive controlled release property. Furthermore, the insecticidal activity of Av-NDs is better than that of avermectin suspension concentrate (Av-SC). The Av-NDs with anti-photolysis and controlled-release characteristics is suitable for large-scale industrial production and is capable to be utilized as effective insecticide in the field.