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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.

(Z)-7-Aryl-5-acyldibenzo[e,g][1,4]diazocin-6(5H)-one, a unique saddle-shaped bridged biaryl containing synchronized aryl-aryl and N-aryl stereogenic axes, was constructed for the first time in good...

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.

An unprecedented tandem carbonylation/aminocarbonylation triggered by palladium-catalyzed enantioselective Heck-type exocyclopalladation delivering chiral heterocyclic α-ketoamides has been developed.

The binding mode of B-norcholesteryl benzimidazole compounds with ct-DNA is the groove mode.

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.

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.

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 IC

Using beeswax as wrapping matrix, two types of release-controlled TM (thiamethoxam)/BK(beeswax-kaolin) microcapsules were prepared by adsorbing TM on kaolin and then encapsulated with beeswax, or directly wrapping TM with beeswax. The structure and morphology of the TM/BK microcapsules were characterized. The effects of different preparation methods, the particle size, pH conditions and different additives on the release property of the TM/BK microcapsules were investigated in water and soil column to compare the advantages of the two approaches. Finally, the insecticidal effect of the TM/BK microcapsules against sugarcane borer and rice planthopper was tested. The results show that the TM/BK microcapsules have a better sustained-release in both water and soil, and the release rate is different under different pH conditions. In addition, the releasing time of the TM/BK microcapsules can be modified by different preparation methods and combination of different additives. In the field applications, the insecticidal activity of the TM/BK microcapsules was better than that of non-sustained control group. Especially in the rice field test, 45 days after the application, the control group lost the activity against rice planthopper because of drug loss, whereas the TM/BK microcapsule group still retained about 90% of the insecticidal activity. The results suggest that the microcapsules have better agricultural application for insect control.

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.

Using polyethylene wax (PW) as the coating matrix, the lambda-cyhalothrin-PW nanosuspoemulsion (LC-PW) with a particle size of 80-150nm was prepared through high-speed stirring, hot melt emulsification and ultrasonic dispersion. The formulation and composition of the LC-PW were optimized, the morphology of the LC-PW was analyzed by dynamic light scattering (DLS) and TEM, and the structure of the LC-PW was characterized by UV and IR. The anti-photolysis test showed that LC-PW had a good anti-photolysis performance. Furthermore, LC-PW could sustainably release Lambda-cyhalothrin, which was pH- and temperature dependent. The insecticidal activity analysis in the greenhouse indicated that the toxic strength between LC-PW and LC-SC (lambda-cyhalothrin-suspension concentrate) to

The simultaneous live-cell imaging of multiple intracellular and disease-related microRNAs (miRNAs) with low abundances is highly important to enhance specificity and accuracy for disease diagnosis. On the basis of the improved cell internalization and accelerated reaction kinetics, we develop a three-dimensional (3D) DNA nanoprobe that integrates intramolecular DNAzyme (intra-Dz) and catalytic hairpin assembly (intra-CHA) amplifications to simultaneously monitor multiple miRNAs in living cells. The sensing components are loaded on a DNA scaffold via the sticky-end hybridization of the DNA sequences to increase the local concentrations of the signal probes. The miRNA-21 and miRNA-155 target sequences can trigger intra-Dz and -CHA amplifications on the nanoprobes to show significantly amplified and distinct fluorescence at different wavelengths for simultaneously monitoring low levels of miRNAs. Real-time fluorescence microscopy reveals that such a 3D DNA nanoprobe design with the intra-Dz and -CHA amplifications can accelerate the reaction rate compared to that of the conventional free Dz and CHA because of the increased local concentrations of the sensing components. Importantly, the 3D DNA nanoprobe has desirable stability and biocompatibility and can be readily delivered into living cells to achieve multiplexed and highly sensitive sensing of intracellular miRNA-155 and miRNA-21 sequences. With the demonstration of its intracellular application, the developed 3D DNA nanoprobe thus holds promising potential for biological studies and accurate disease diagnosis.

By means of high-speed emulsification and ultrasonic dispersing, emamectin benzoate (EB)–sodium lignosulfonate (SL) nanoformulation (EBSLNf) with a particle size of 150–250 nm was developed by the ...

An efficient and “green” protocol for the synthesis of 3-acylimidazo[1,2-a]pyridines through intramolecular oxidative α-amination of carbonyl compounds has been developed. The reaction proceeds smoothly utilizing I2 as a catalyst and H2O2 as an oxidant under neat condition with broad substrate scope. Several complex nitrogen-containing fused rings are conveniently constructed, which are not easy to access by traditional methods.

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, IC

The simultaneous imaging of the dynamic expression variations of regulatory RNAs in cells, which remains a major challenge, has important applications in precise disease diagnosis, treatment and prognosis. Here, we describe the establishment of a biodegradable ZnO nanoparticle (NP)-assisted asymmetric amplification approach for the simultaneous imaging of microRNA-21 (miRNA-21) and programmed cell death 4 (PDCD4) mRNA at distinct expression levels in live cells. The DNA signal probe complexes are immobilized on the ZnO NPs and readily delivered into the target cancer cells via the endocytosis pathway. The acidic microenvironment in cancer cells leads to the dissolution of the ZnO NPs to release Zn2+ ions and the intracellular miRNA-21 activates the Zn2+-dependent DNAzyme to cleave the substrate signal probes with the assistance of the Zn2+ cofactor to show green fluorescence for imaging miRNA-21. Meanwhile, the PDCD4 mRNA can displace the other quenched signal probes to generate red fluorescence. Importantly, the PDCD4 mRNA sequences can be recycled and reused by using the DNAzyme-cleaved sequences as the fuel strands through two strand displacement reactions to yield amplified red fluorescence for detecting low levels of PDCD4 mRNA. Moreover, our approach can be used to evaluate the varied expression levels of miRNA-21 and PDCD4 mRNA responsive to different drugs in cells, reflecting its usefulness for precise cancer diagnosis and prognosis upon anticancer drug treatment.

In this work, a series of Biotin-substituted B-nor-cholesteryl benzimidazole compounds were synthesized. The antiproliferative activities of these compounds were evaluated in vitro using a series of human cancer cell lines, including HeLa (cervical cancer), SKOV3 (ovarian cancer), T-47D (thymus gland cancer), MCF-7 (human breast cancer) and HEK293T (normal renal epithelial) cells. These compounds displayed distinct antiproliferative activities against the currently tested cancer cells. The apoptotic properties induced by compound 6d were further investigated. Our results showed that compound 6d could induce the apoptosis of SKOV3 cells, blocking the cell growth in S-phase. Western blotting analyses revealed that compound 6d can induce cell apoptosis via the mitochondria-dependent pathway.

The current study aims to evaluate the antiproliferative activity of B-norcholesteryl benzimidazole compounds in human ovarian cancer cells (SKOV3). Our experimental data indicates that the tested compounds can induce apoptosis in SKOV3 cells, block S-phase growth, and decrease mitochondrial membrane potential. Western blot results showed that B-norcholesteryl benzimidazole compounds (1 and 2) induced apoptosis in SKOV3 cells via activation of the mitochondrial signaling pathway. Following SKOV3 cells treatment with compounds 1 and 2, the cell metabolism was assessed using the UHPLC-QE-MS (Ultra High Performance Liquid Chromatography-Q Exactive Orbitrap- Mass Spectrometry) non-target metabolomics analysis method. The results showed 10 metabolic pathways that mediated the effects of compound 1, including arginine and proline metabolism; alanine, aspartate, and glutamate metabolism; histidine metabolism; D-glutamine and D-glutamine and D-glutamate metabolism; cysteine and methionine metabolism; aminoacyl-tRNA biosynthesis; purine metabolism; Glutathione metabolism; D-Arginine and D-ornithine metabolism; and Nitrogen metabolism. From the perspective of metabolomics, compound 1 inhibits intracellular metabolism, protein synthesis, and slows down energy metabolism in SKOV3 cells. These changes result in the inhibition of proliferation and signal transduction, abrogate invasive and metastatic properties, and induce apoptosis, thus, exerting anti-tumor effects. Application of compound 2 altered activation of metabolic pathways in SKOV3 cells. The main metabolic pathways involved were glycerophospholipid metabolism; arginine and proline metabolism; purine metabolism; glycine, serine, and threonine metabolism; and ether lipid metabolism. The metabolic pathway with the greatest impact and the deepest enrichment was the glycerophospholipid metabolism. In conclusion, compound 2 inhibits proliferation of SKOV3 cells by interfering with glycerate metabolism, which plays a major role in regulation of cell membrane structure and function. Additionally, compound 2 can inhibit the invasion and metastasis of SKOV3 cells and induce apoptosis via interfering with the metabolism of arginine and proline.

The sensing of intracellular microRNAs (miRNAs) is of significance for early-stage disease diagnosis and therapeutic monitoring. DNA is an interesting building material that can be programed into assemblies with rigid and branched structures, especially suitable for imaging intracellular biomolecules or therapeutic drug delivery. Here, by introducing the palindromic sequences into the programmable DNA hairpins, we describe an endogenous target-responsive three-way branched and palindrome-assisted catalytic hairpin assembly (3W-pCHA) approach for imaging miRNA-155 of living tumor cells with high sensitivity. The miRNA-155 triggers autonomous assembly of the fluorescently quenched signal hairpin and two hairpin dimers formed via hybridization of their respective palindromic sequences to yield branched DNA junctions, which carry the unopened hairpins and thus provide addressable substrates for continuous assembly formation of DNA nanostructures. During the formation of the DNA nanostructures, the miRNA-155 is cyclically reused and many signal probes are unfolded to show highly intensified fluorescence for detecting miRNA-155 down to 6.9 pM in vitro with high selectivity. More importantly, these probes can be transfected into live cancer cells to initiate the assembly process triggered by intracellular miRNA-155, which provides a new way for imaging highly under-expressed miRNAs in cells. Besides, this approach can also be employed to differentiate miRNA-155 expression variations in different cells, indicating its promising potentials for early-stage disease diagnosis and biological studies in cells.

An efficient and green protocol for the synthesis of acylated imidazo[1,2-a]pyridines and indolizines via intramolecular dehydrogenative aminooxygenation of alkynes has been developed. The reaction proceeds smoothly utilizing I2 as a catalyst and TBHP as an oxidant with a broad substrate scope. Mechanism studies reveal that the reaction maybe experiences a hydration followed by an oxidative cycloamination process.

Background: The modification of steroidal structure is commonly used to change the biological activity of steroids in medicinal chemistry. Some steroids containing heterocycles exhibit distinct cytotoxicity against various cancer cell lines and have been receiving wide attention over the years by medicinal chemists for drug discovery. Methods: Using pregnenolone and stigmasterol as starting materials, via different chemical reaction, two series of heterosteroids with side chain of 20- and 22-hydrazone aromatic cycles or heterocycles in their structures were synthesized and characterized by IR, NMR and HRMS. The antiproliferative activity of the compounds in vitro was evaluated against human HT-29, HeLa, Bel 7404 and SGC 7901 cancer cells by MTT assays. Results: The steroidal compounds with side chain of 20-hydrazone aromatic cycles or heterocycles exhibited distinct cytotoxicity. However, analogues with the side chain of 22-hydrazone resulted in a dramatic decrease of the cytotoxicity. The result of Annexin V assay showed that the 20-hydrazone compounds were potent apoptotic inducers against these carcinoma cells. Conclusion: Steroidal compounds with the side-chain of 20-hydrazone aromatic heterocycles exhibit distinct antiproliferative activity in vitro. However, the compounds with the side-chain of 22-hydrazone aromatic heterocycle decreased the cytotoxicity of the compounds.

Hexamethylene bis-acetamide inducible protein 1 (HEXIM1) is identified as a novel inhibitor of estrogen stimulated breast cell growth, and it suppresses estrogen receptor-α transcriptional activity. HEXIM1 protein level has been found to be downregulated by estrogens. Recently, HEXIM1 has been found to inhibit androgen receptor transcriptional activity as well. Researchers have used Hexamethylene bis-acetamide (HMBA) for decades to stimulate HEXIM1 expression, which also inhibit estrogen stimulated breast cancer cell gene activation and androgen stimulated prostate cancer gene activation. However, the direct molecular targets of HMBA that modulate the induction of HEXIM1 expression in mammalian cells have not been identified. Based on HMBA and its more potent analog 4a1, we designed molecular probes to pull down the binding proteins of these compounds. Via proteomic approach and biological assays, we demonstrate that HMBA and 4a1 are actually heat shock protein 70 (HSP70) binders. The known HSP70 activator showed similar activity as HMBA and 4a1 to induce HEXIM1 expression, suggesting that HMBA and 4a1 might be putative HSP70 activators. Molecular target identification of HMBA and 4a1 could lead to further structural optimization of the parental compound to generate more potent derivatives to stimulate HEXIM1 expression, which could be a novel approach for hormone dependent breast cancer and prostate cancer treatment.

Three series of novel steroidal thiazole derivatives were synthesized by microwave assisted one-pot reaction from pregnenolone, testosterone and estrone, respectively. Their structures were characterized by IR, NMR and HRMS, and the antiproliferative activities of all the synthesized compounds against human cervical carcinoma (HeLa), human liver carcinoma(HepG2), human lung carcinoma(A549), nasopharyngeal carcinoma(CNE2) and normal kidney epithelial cells(HEK293T) were screened. Among the compounds, 1-estron-17′-ylidene-2-[4′-(p-bromophenyl)-2′-thiazol] hydrazone(12) displayed distinct antiproliferative activity against all the tested cancer cell lines and was almost inactive to normal kidney epithelial cells.

Histone deacetylase (HDAC) inhibitors modulate various cellular functions including proliferation, differentiation, and apoptosis. Vorinostat (SuberAniloHydroxamic Acid, SAHA) is the first HDAC inhibitor approved by FDA for cancer treatment. However, SAHA distributes in cancer tissue and normal tissue in similar levels. It will be ideal to selectively deliver SAHA into cancer cells. Rapidly growing cancer cells have a great need of cholesterol. Low-density lipoprotein (LDL) is the major cholesterol carrier in plasma and its uptake is mediated by LDL-receptor (LDL-R), a glycoprotein overexpressed on the surface of cancer cells. Herein, we designed and synthesized a SAHA cholesterol conjugate, and further formed the conjugate containing particles with LDL as the carrier. The diameters of the particles were determined. The inhibitory activity of the particles carrying the conjugate was determined with cancer cell proliferation assay, and the hydrolysis of the conjugate by the enzymes in cancer cells was confirmed with LC-MS/MS.

This study evaluated the relationship between urine mercury (UHg) concentrations and renal function (serum creatinine (SCr) and blood urea nitrogen (BUN)) in delivery women in the Wanshan mercury (Hg) mining area. Leishan County was selected as the control area. 165 and 65 maternal samples were collected from the Wanshan and Leishan area, respectively. The geometric means of UHg concentrations were 1.09 and 0.29 μg/L in Wanshan and Leishan subjects, respectively. Significant differences (p 0.01) of UHg were observed between the two populations, indicating the potential risks of inorganic Hg exposure in the Wanshan population. The median (interquartile range) values of SCr were 69.1 (12.5) μmol/L and 46.0 (11.0) μmol/L for the Wanshan and Leishan populations, respectively, indicating significant differences (p 0.01) between the two groups. However, no significant differences among BUN values for the two groups were observed. A significant positive correlation (r = 0.385, p 0.001) was observed between UHg concentration and SCr in the study population. The odds ratio (OR) value of UHg in Wanshan area was 9.29 times higher than that in Leishan area (95% confidence interval (CI): 3.58-24.1). The OR value of SCr decrease in patients with low UHg was 0.32 times higher than that in patients with high UHg (95% CI: 0.19-0.55). The OR value of SCr decrease in the population with fish consumption was 0.71 times higher than that of the population without fish consumption (95% CI: 0.58-0.88). In conclusion, maternal IHg exposure caused impaired renal function and fish consumption may play a role in preventing Hg-induced nephrotoxicity.

Despite the fact that the identification and detection of circulating tumor cells (CTCs) plays a critical role in cancer monitoring and diagnosis, it remains a major challenge to isolate and detect these cells, due to their extreme scarcity in peripheral blood. In this work, by coupling a dual recognition strategy and the commercial personal glucose meter, we established a point-of-care approach for detecting rare CTCs in whole blood with high sensitivity and selectivity. The antibody-conjugated magnetic beads lead to the capture and isolation of the CTCs while the enzyme- and second antibody-modified microspheres yield the signal for detection. Because of the dual recognition format, the developed method is highly selective, and a low detection limit of 7 cells can be realized as well, owing to the great signal amplification through the enzyme-loaded microbead labels. More importantly, the detection of CTCs in whole blood can be achieved in a point-of-care fashion with the using of the glucose meter transducer, offering our method a convenient and attractive alternative to traditional biopsy for the diagnosis of various cancers.

An efficient and "green" protocol for the synthesis of 3-acylimidazo[1,2

Certain B-norcholesteryl benzimidazole compounds were found to mediate marked anti-tumor proliferative effects in vitro in our earlier study. Here, the mechanism of action of these anti-tumor effects was evaluated using HeLa human cervical cancer cells. Methods for detecting cell invasion and migration, Annexin V-PI double staining, cell cycle status, and mitochondrial membrane potential Δψm were employed. These compounds were confirmed to significantly inhibit the proliferation of HeLa cells in vitro. Compound 1 induced apoptosis in S phase, compound 2induced apoptosis in the G0/G1 phase and compound 3 induced late apoptosis in the G2/M phase. These compounds induced HeLa cell apoptosis through depolarization of mitochondrial membrane potential Δψm in a dose-dependent manner. B-norcholesteryl benzimidazole compounds induced morphological changes in HeLa cells and inhibited proliferation, invasion and metastasis. Apoptosis was promoted by mechanisms involving p21 and p53 in this cervical cancer cell line.

Using cholesterol as a starting material, two novel steroidal thiadiazole derivatives possessing a structure of A-homo lactam and a B-nor steroidal skeleton were designed and synthesized by six steps of reactions, and their antiproliferative activities were assayed against various cancer cell lines. The result shows that compound 7b displays an excellent selective inhibition to A-549 (human lung carcinoma) cancer cell lines with an IC50 value of 8.0 μM.

A practical method for the umpolung selenocyanation of aryl ketones, alkyl ketones, β-ketoesters and electron-rich arenes has been developed, affording various selenocyanates in moderate to excellent yields. This transformation proceeds by an oxidative umpolung selenocyanation through nitrogen oxides-mediated electrophilic selenocyanation process. This method is simpler, more efficient, and less costly than precedent methods. Further transformations of the arylselenocyanate was performed to prove the synthetic utility of this methodology.

The study of molecule-DNA interaction is very important for designing an improved therapeutic agent. In previous studies, we synthesized some B-norcholesteryl benzimidazole compounds, and the tests on cancer cells showed that these compounds had good in vitro anti-cancer activities. In order to further investigate mechanism of their actions, three different B-norcholesteryl benzimidazole compounds were selected and interaction of these compounds with the calf thymus DNA (ct-DNA) was monitored by using various methods including UV–Vis and fluorescence spectroscopic techniques, viscosity measurement, and circular dichroism (CD). The results proved a hypochromic effect accompanied with a slight red-shift due to the interaction of the molecules with ct-DNA. According to the UV-Vis and fluorescence spectra, the mentioned compounds were bound to DNA, preferentially through partial intercalation into the DNA helix. Moreover, the ethidium bromide (EB) and Hoechst 33258 competitive binding experiments were also used to confirm the interaction mode of the compounds with ct-DNA. In the Hoechst 33258 displacement experiment, no significant change in the fluorescence intensity was observed. Additional assays such as iodide quenching, viscosity, and CD spectroscopy further confirmed that intercalation should be the major binding mode of the selected compounds with DNA. The cytotoxicity of these three compounds was also evaluated by MTT method, and the results confirmed that binding ability of these compounds to DNA was consistent with their cytotoxicity behavior. The experimental results indicated a higher binding affinity for compound 3 compared to the other compounds. This research provided a better understanding on the molecular mechanism of the interaction between B-norcholesteryl benzimidazole compounds and tumor cells, and offered a beneficial perspective to the designation of novel B-norsteroidal anticancer compounds.

Using pregnenolone as a starting material, some 3-substituted 17-[1',2',3']-selenadiazolylpregnenolone derivatives were synthesized, and their structures were characterized by IR, NMR and HRMS. The in vitro antitumor activity of the compounds was assayed against PC-3、SKOV3、T47D、MCF-7 and HEK293T cell lines. The results show that some compounds display selective antiproliferative activity against PC-3 and SKOV3 cells lines and are almost inactive to normal kidney epithelial cells (HEK293T). The IC50 value are much better than that of abiraterone (positive control).

The monitoring and imaging of intracellular microRNAs (miRNAs) with specific sequences plays a vital role in cell biology as it can potentially elucidate many cellular processes and diseases related to miRNAs in living cells with accurate information. However, the detection of trace amounts of under-expressed intracellular miRNAs in living cells represents one of the current major challenges. In an effort to address this issue, we describe the establishment of an in cell catalytic hairpin assembly (CHA) signal amplification strategy for imaging under-expressed intracellular miRNAs in this work. Gold nanoparticles functionalized with FAM- and TAMRA-labeled hairpins with disulfide bonds in the stems are readily delivered into cells via endocytosis. Glutathione with evaluated concentrations in cancer cells cleaves the disulfide bonds in the hairpins by reduction to release the hairpins, and the target miRNAs further trigger CHA between the two hairpins to form many DNA duplexes, which bring the FAM and TAMRA labels into close proximity to generate apparently enhanced fluorescence resonance energy transfer (FRET) for the sensitive monitoring of low amounts of under-expressed miRNAs in live cancer cells. Using CHA to amplify the signal output and FRET to reduce the background noise, a significantly enhanced signal-to-noise ratio, thereby high sensitivity, over conventional fluorescence imaging can be realized, making our method particularly suitable for monitoring low levels of intracellular species.

The development of sensitive and simple approaches capable of monitoring trace amounts of protein biomarkers is appealing for disease diagnosis and treatment. Towards this end, we have developed an electrochemical sensing platform for sensitive and simple detection of protein biomarkers by using thrombin as the model target molecules via a target-programmed proximity binding amplification approach. The binding of thrombin to the aptamer sequences in the partial dsDNA duplex probes induces the release of the ssDNA trigger strands, which catalyze subsequent assembly formation of many methylene blue (MB)-tagged proximate DNA motifs with the presence of the DNA fuel strands through cascaded toehold-mediated strand displacement reactions. Due to the proximity-binding effect, these MB-tagged proximate DNA motifs anneal with the capture probes on the sensor surface with significantly enhanced stability against the corresponding single component counterpart, thereby pulling the MB tags close to the sensor surface and generating substantially amplified signal responses for sensitive determination of thrombin down to 23.6 pM. In addition, such aptasensor can specifically discriminate thrombin from other interference proteins, and can also be utilized to monitor thrombin in diluted serum samples, demonstrating its great potential for sensitive determination of proteins for early disease diagnosis.

Using cholesterol, stigmasterol and sitosterol as starting materials, a series of 7-subsitituted-ster-3-yl 2-methoxybenzoate analogs were prepared through reacting with 2-methoxybenzoyl chloride and introducing some function groups, such as carbonyl, hydroxyl and various thiosemicarbazones, at 7-position of steroidal nucleus. The structures of these new compounds were characterized by IR, NMR and HRMS. Their antiproliferative activities were evaluated by using several types of cancer cells. Interestingly, the compounds displayed potent antiproliferative activity against CNE-2 (nasopharyngeal carcinoma cell lines), BEL-7402 (human liver cancer cell lines) and HepG2 (human liver cancer cell lines), suggesting that they have potential to be drug candidates for cancer treatment.

Taking orostanal (a compound from a Japanese marine sponge, Stelletta hiwasaensis) as a lead compound, some novel B-norcholesteryl benzimidazole and benzothiazole derivatives were synthesized. The antiproliferative activity of the compounds against human cervical carcinoma (HeLa), human lung carcinoma (A549), human liver carcinoma cells (HEPG2) and normal kidney epithelial cells (HEK293T) was assayed. The results revealed that the benzimidazole group was a better substituent than benzothiazole group for increasing the antiproliferative activity of compounds. 2-(3β′-Acetoxy-5β′-hydroxy-6′-B-norcholesteryl)benzimidazole (9b) with the structure of 6-benzimidazole displays the best antiproliferative activity to the cancer cells in all compounds, but is almost inactive to normal kidney epithelial cells (HEK293T). The assay of compound 9b to cancer cell apoptosis by flow cytometry showed that the compound was able to effectively induce cancer cell apoptosis. The research provided a theoretical reference for the exploration of new anti-cancer agents and may be useful for the design of novel chemotherapeutic drugs.

Here a series of dehydroepiandrosterone-17-hydrazone and estrone-17-hydrazone derivatives possessing various aromatic heterocycle structures in 17-side chain of their steroidal nucleus were synthesized and their structures were evaluated. The antiproliferative activity of synthesized compounds against some cancer cells was investigated. The results have demonstrated that some dehydroepiandrosterone-17-hydrazone derivatives show distinct antiproliferative activity against some cancer cells through inducing cancer cell apoptosis, and compound 8 with a quinoline structure in 17-side chain displays excellent antiproliferative activity in vitro against SGC 7901 cancer cell (human gastric carcinoma) with an IC50 value of 1 μM. In addition, estrone-17-hydrazone derivatives having a key feature of indole group in the structure showed a special obvious cytotoxicity against HeLa cells, but almost inactive against other cells. The information obtained from the studies is valuable for the design of novel steroidal chemotherapeutic drugs.

A series of 3-substituted-6-aza-B-homo-5-α-stigmastan-7-one and 3-substituted-6-aza-B-homo-5-α-sitostan-7-one derivatives were designed and synthesized by the oxidation, reduction, oximation, Beckman rearrangement and condensation reaction. Their structures were characterized. The antiproliferative activities were assayed, and some of the compounds synthesized displayed distinct cytotoxicity against SGC 7901, CNE, HeLa and Bel 7404 cancer cells. Our results revealed that the compounds with the side chain of sitosterol had better antiproliferative activity than the compounds with the side chain of stigmasterol. The compound 11b with 3-thiosemicarbazone and 12b with 3-(4′-methyl)thiosemicarbazone group displayed an excellent antiproliferative activity against Bel-7404 cells owning an IC50 value of 3.9 and 5.6 μM, respectively (compared with cisplatin, IC50: 11.6 μM). The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.