Publications by authors named "Chunfang Gan"

38 Publications

Fabrication and evaluation of Lambda-Cyhalothrin nanosuspoemulsion with pH- and temperature-responsive based on polyethylene wax as carrier.

J Environ Sci Health B 2021 13;56(8):741-752. Epub 2021 Aug 13.

Guangxi Key Laboratory of Natural Polymer Chemistry and Physics, Nanning Normal University, Nanning, PR China.

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 was similar within the same concentration ranges tested, but the insecticidal duration of LC-PW was significantly longer than LC-SC. Thus, the new type of LC-PW with the properties of anti-photolysis and controlled release is suitable for application in the field as a better insecticide.
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http://dx.doi.org/10.1080/03601234.2021.1941705DOI Listing
August 2021

3D DNA Scaffold-Assisted Dual Intramolecular Amplifications for Multiplexed and Sensitive MicroRNA Imaging in Living Cells.

Anal Chem 2021 07 7;93(28):9912-9919. Epub 2021 Jul 7.

Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, P. R. China.

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.
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http://dx.doi.org/10.1021/acs.analchem.1c02124DOI Listing
July 2021

Apoptosis inducing properties of 3-biotinylate-6-benzimidazole B-nor-cholesterol analogues.

Steroids 2021 05 12;169:108822. Epub 2021 Mar 12.

Guangxi Key Laboratory of Natural Polymer Chemistry and Physics, Key Laboratory of Beibu Gulf Environment Change and Resources Utilization, School of Chemistry and Material, Nanning Normal University, Nanning 530001, PR China. Electronic address:

In this work, a series of Biotin-substituted B-nor-cholesteryl benzimidazole compounds were synthesized. The antiproliferativeactivities 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.
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http://dx.doi.org/10.1016/j.steroids.2021.108822DOI Listing
May 2021

Studies on apoptosis induced by B-norcholesteryl benzimidazole compounds in HeLa cells.

Steroids 2021 04 13;168:108802. Epub 2021 Feb 13.

Guangxi Key Laboratory of Natural Polymer Chemistry and Physics, Key Laboratory of Beibu Gulf Environment Change and Resources Utilization, School of Chemistry and Material, Nanning Normal University, Nanning 530001, PR China. Electronic address:

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 Δψ 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 G/G phase and compound 3 induced late apoptosis in the G/M phase. These compounds induced HeLa cell apoptosis through depolarization of mitochondrial membrane potential Δψ 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.
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http://dx.doi.org/10.1016/j.steroids.2021.108802DOI Listing
April 2021

Biodegradable nanoparticle-assisted and multiplexed imaging of asymmetric RNA expressions in live cells for precise cancer diagnosis and prognosis.

Nanoscale 2020 Dec 26;12(47):24100-24106. Epub 2020 Nov 26.

Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, P. R. China.

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 Zn ions and the intracellular miRNA-21 activates the Zn-dependent DNAzyme to cleave the substrate signal probes with the assistance of the Zn 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.
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http://dx.doi.org/10.1039/d0nr07156kDOI Listing
December 2020

Untargeted metabolomics study and pro-apoptotic properties of B-norcholesteryl benzimidazole compounds in ovarian cancer SKOV3 cells.

J Steroid Biochem Mol Biol 2020 09 11;202:105709. Epub 2020 Jun 11.

Guangxi Key Laboratory of Natural Polymer Chemistry and Physics, Key Laboratory of Beibu Gulf Environment Change and Resources Utilization, School of Chemistry and Material, Nanning Normal University, Nanning 530001, PR China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jsbmb.2020.105709DOI Listing
September 2020

Release-controlled microcapsules of thiamethoxam encapsulated in beeswax and their application in field.

J Environ Sci Health B 2020 1;55(4):342-354. Epub 2019 Dec 1.

Guangxi Key Laboratory of Natural Polymer Chemistry and Physics, Nanning Normal University, Nanning, PR China.

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.
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http://dx.doi.org/10.1080/03601234.2019.1697588DOI Listing
May 2020

Maternal inorganic mercury exposure and renal effects in the Wanshan mercury mining area, southwest China.

Ecotoxicol Environ Saf 2020 Feb 26;189:109987. Epub 2019 Nov 26.

School of Public Health, Guizhou Medical University, Guiyang, 550025, China; Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 550025, China; State Key Laboratory of Environmental Geochemistry, Institute of Geochemistry, Chinese Academy of Sciences, Guiyang, 550081, China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ecoenv.2019.109987DOI Listing
February 2020

Study on the interactions between B-norcholesteryl benzimidazole compounds with ct-DNA.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Feb 31;227:117525. Epub 2019 Oct 31.

Guangxi Key Laboratory of Natural Polymer Chemistry and Physics, Key Laboratory of Beibu Gulf Environment Change and Resources Utilization, School of Chemistry and Material, Nanning Normal University, Nanning, 530001, PR China; Guangxi Colleges and University Key Laboratory of Beibu Gulf Oil and Natural Gas Resource Effective Utilization, Beibuwan University, Qinzhou, 535099, PR China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.saa.2019.117525DOI Listing
February 2020

Synthesis and antiproliferative evaluation of novel steroid-benzisoselenazolone hybrids.

Steroids 2019 12 20;152:108502. Epub 2019 Sep 20.

Guangxi Key Laboratory of Natural Polymer Chemistry and Physics, Nanning Normal University, Nanning 530001, PR China. Electronic address:

The two different types of steroidal benzisoselenazolone hybrids were synthesized by incorporating benzisoselenazolone scaffold into dehydroepiandrosterone and B-norcholesterol. The antiproliferative activity of the synthesized compounds against some carcinoma cell lines were investigated. The results showed that some of these compounds have better inhibitory activity than abiraterone on the proliferation of tumor cells associated with human growth hormone, and have less cytotoxicity on normal human cells. In particular, the IC values of the compound 8a and 8f are 5.4 and 6.5 µmol/L against human ovarian carcinoma (SKOV3) cell line, and possess SI values of 13.9 and 10.5, respectively. The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.
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http://dx.doi.org/10.1016/j.steroids.2019.108502DOI Listing
December 2019

Highly specific and sensitive point-of-care detection of rare circulating tumor cells in whole blood via a dual recognition strategy.

Biosens Bioelectron 2019 Oct 21;143:111604. Epub 2019 Aug 21.

Key Laboratory of Luminescent and Real-Time Analytical Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, PR China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.bios.2019.111604DOI Listing
October 2019

Synthesis and antiproliferative activity of 17-[1',2',3']-selenadiazolylpregnenolone compounds.

Steroids 2018 12 6;140:151-158. Epub 2018 Oct 6.

College of Chemistry and Material Science, Guangxi Teachers Education University, Nanning 530001, PR China. Electronic address:

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 IC value are much better than that of abiraterone (positive control).
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http://dx.doi.org/10.1016/j.steroids.2018.10.004DOI Listing
December 2018

Bio-cleavable nanoprobes for target-triggered catalytic hairpin assembly amplification detection of microRNAs in live cancer cells.

Nanoscale 2018 Sep;10(37):17623-17628

Key Laboratory on Luminescence and Real-Time Analysis, Ministry of Education, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, P. R. China.

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.
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http://dx.doi.org/10.1039/c8nr05229hDOI Listing
September 2018

Target-programmed and autonomous proximity binding aptasensor for amplified electronic detection of thrombin.

Biosens Bioelectron 2018 Oct 14;117:743-747. Epub 2018 Jul 14.

Key Laboratory of Luminescent and Real-Time Analytical Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.bios.2018.06.069DOI Listing
October 2018

Synthesis, characterization, and biological evaluations of some steryl 2-methoxybenzoates as anticancer agents.

Nat Prod Res 2019 Apr 30;33(8):1101-1105. Epub 2018 Mar 30.

a College of Chemistry and Material Science , Guangxi Teachers Education University , Nanning , China.

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.
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http://dx.doi.org/10.1080/14786419.2018.1457662DOI Listing
April 2019

Synthesis and Cytotoxic Evaluation of Steroidal Copper (Cu (II)) Complexes.

Bioinorg Chem Appl 2017 18;2017:4276919. Epub 2017 Oct 18.

Key Laboratory of Beibu Gulf Environment Change and Resources Utilization, College of Chemistry and Material Science, Guangxi Teachers Education University, Nanning 530001, China.

Using estrone and pregnenolone as starting materials, some steroidal copper complexes were synthesized by the condensation of steroidal ketones with thiosemicarbazide or diazanyl pyridine and then complexation of steroidal thiosemicarbazones or steroidal diazanyl pyridines with Cu (II). The complexes were characterized by IR, NMR, and HRMS. The synthesized compounds were screened for their cytotoxicity against HeLa, Bel-7404, and 293T cell lines in vitro. The results show that all steroidal copper (II) complexes display obvious antiproliferative activity against the tested cancer cells. The IC values of complexes and against Bel-7404 (human liver carcinoma) are 5.0 and 7.0 M.
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http://dx.doi.org/10.1155/2017/4276919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664251PMC
October 2017

Copalic acid analogs down-regulate androgen receptor and inhibit small chaperone protein.

Bioorg Med Chem Lett 2017 06 13;27(11):2292-2295. Epub 2017 Apr 13.

Department of Chemistry, Center for Gene Regulation in Health and Disease, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA. Electronic address:

Copalic acid, one of the diterpenoid acids in copaiba oil, inhibited the chaperone function of α-crystallin and heat shock protein 27kD (HSP27). It also showed potent activity in decreasing an HSP27 client protein, androgen receptor (AR), which makes it useful in prostate cancer treatment or prevention. To develop potent drug candidates to decrease the AR level in prostate cancer cells, more copalic acid analogs were synthesized. Using the level of AR as the readout, 15 of the copalic acid analogs were screened and two compounds were much more potent than copalic acid. The compounds also dose-dependently inhibited AR positive prostate cancer cell growth. Furthermore, they inhibited the chaperone activity of α-crystallin as well.
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http://dx.doi.org/10.1016/j.bmcl.2017.04.046DOI Listing
June 2017

HMBA is a putative HSP70 activator stimulating HEXIM1 expression that is down-regulated by estrogen.

J Steroid Biochem Mol Biol 2017 04 14;168:91-101. Epub 2017 Feb 14.

Department of Chemistry, Center for Gene Regulation in Health and Disease, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH, 44115, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jsbmb.2017.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5699885PMC
April 2017

Synthesis of Vorinostat and cholesterol conjugate to enhance the cancer cell uptake selectivity.

Bioorg Med Chem Lett 2017 02 10;27(4):816-820. Epub 2017 Jan 10.

Department of Chemistry, Center for Gene Regulation in Health and Disease, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.bmcl.2017.01.025DOI Listing
February 2017

Synthesis of some steroidal derivatives with side chain of 20- and 22-hydrazone aromatic heterocycles and their antiproliferative acitivity.

Med Chem 2016 Dec 5. Epub 2016 Dec 5.

College of Chemistry and Material Science, Guangxi Teachers Education University, Nanning 530001, China; Guangxi Colleges and Universities Key Laboratory of Beibu Gulf Oil and Natural Gas Resource Effective Utilization, Qizhou University, Qinzhou, China.

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 gotten 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.
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December 2016

Indomethacin derivatives as tubulin stabilizers to inhibit cancer cell proliferation.

Bioorg Med Chem 2016 Jan 9;24(2):277-85. Epub 2015 Dec 9.

Department of Chemistry, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA; Center for Gene Regulation in Health and Disease, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA. Electronic address:

Cyclooxygenase (COX) inhibitor Indomethacin analogs exhibited more potent cancer cell growth inhibition and apoptosis inducing activities than the parental compound. The anti-proliferative mechanism investigation of the analogs revealed that they inhibited tubulin polymerization at high concentrations whereas enhanced polymerization at low concentrations. The two opposite activities might antagonize each other and impaired the anti-proliferative activity of the derivatives eventually. In this study, we further performed lead optimization based on the structure activity relationship (SAR) generated. One of the new Indomethacin derivatives compound 11 {2-(4-(benzyloxy)phenyl)-N-(1-(4-bromobenzoyl)-3-(2-((2-(dimethylamino)ethyl)amino)-2-oxoethyl)-2-methyl-1H-indol-5-yl)acetamide} inhibited the proliferation of a panel of cancer cell lines with IC50s at the sub-micromole levels. Further study revealed that the compound only enhanced tubulin polymerization and was a tubulin stabilizer.
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http://dx.doi.org/10.1016/j.bmc.2015.12.016DOI Listing
January 2016

Synthesis and Antiproliferative Activity of Steroidal Thiosemicarbazone Platinum (Pt(II)) Complexes.

Bioinorg Chem Appl 2015 8;2015:742592. Epub 2015 Oct 8.

College of Chemistry and Materials Science, Guangxi Teachers Education University, Nanning 530001, China ; Guangxi Colleges and University Key Laboratory of Beibu Gulf Oil and Natural Gas Resource Effective Utilization, Qizhou University, Qizhou 535000, China.

Steroidal compounds exhibit particular physiological activities. In this paper, some steroidal thiosemicarbazones platinum (Pt(II)) complexes were synthesized by the condensation of steroidal ketones with thiosemicarbazide using estrone, chenodeoxycholic acid, and 7-deoxycholic acid as starting materials and complexation of steroidal thiosesemicarbazones with Pt(II). The complexes were characterized by IR, NMR, and MS, and their antiproliferative activities were evaluated. The results showed that some steroidal thiosemicarbazones platinum (Pt(II)) complexes displayed moderate cytotoxicity to HeLa and Bel-7404 cells. Thereinto, complex 6 showed an excellent inhibited selectivity to HeLa cells with an IC50 value of 9.2 μM and SI value of 21.7. At the same time, all compounds were almost inactive to HEK293T (normal kidney epithelial cells). The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.
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http://dx.doi.org/10.1155/2015/742592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618117PMC
December 2015

Synthesis and in vitro antiproliferative evaluation of some B-norcholesteryl Benzimidazole and Benzothiazole derivatives.

Mar Drugs 2015 Apr 22;13(4):2488-504. Epub 2015 Apr 22.

College of Chemistry and Material Science, Guangxi Teachers Education University, Nanning 530001, China.

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.
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http://dx.doi.org/10.3390/md13042488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413222PMC
April 2015

Synthesis and antiproliferative evaluation of some novel B-nor-D-homosteroids.

Steroids 2015 Jun 23;98:138-42. Epub 2015 Mar 23.

College of Chemistry and Materials Science, Guangxi Teachers Education University, Nanning 530001, China. Electronic address:

Using 3β-hydroxy-5-androsten-17-one as a starting material, a series of novel nitrogen-containing B-nor-D-homosteroids were designed and synthesized by the oximation, Beckman rearrangement, ozonation, cyclization and condensation reaction. The structures of all new compounds were determined by analysis of their NMR, MS and IR spectra. The antiproliferative activity of compounds was evaluated against HT-29 (colonic carcinoma), HeLa (human cervical carcinoma) and Bel 7404 (human liver carcinoma) cells.
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http://dx.doi.org/10.1016/j.steroids.2015.03.012DOI Listing
June 2015

Synthesis, characterization and antitumor activities of some steroidal derivatives with side chain of 17-hydrazone aromatic heterocycle.

Steroids 2015 Mar 9;95:32-8. Epub 2015 Jan 9.

College of Chemistry and Material Science, Guangxi Teachers Education University, Nanning 530001, China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.steroids.2015.01.002DOI Listing
March 2015

Synthesis and antiproliferative activity of some steroidal thiosemicarbazones, semicarbazones and hydrozones.

Steroids 2014 Sep 11;87:99-107. Epub 2014 Jun 11.

College of Chemistry and Life Science, Guangxi Teachers Education University, Nanning 530001, China. Electronic address:

Steroidal thiosemicarbazones, semicarbazones and hydrazones have received extensive attention of scientists recently because they exhibit some biological activities such as antibacterial, antiviral and anticancer. Using different steroids as starting materials, through different chemical methods, 24 steroidal compounds with thiosemicarbazone, semicarbazone or hydrazone groups in their structures, were synthesized, characterized by IR, NMR and MS. The antiproliferative activity of the compounds was evaluated against human gastric cancer (SGC-7901) and human liver cancer (Bel-7404) cells. The structure-activity relationship of these compounds was discussed. The results showed that compound 3 and 12a-12c exhibited significant inhibitory activity to Bel-7404 cells, and IC50 values of them were 4.2, 11.0, 7.4 and 15.0μM respectively (Cisplatin, IC50: 11.6μM).
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http://dx.doi.org/10.1016/j.steroids.2014.05.026DOI Listing
September 2014

Synthesis and evaluation of some new aza-B-homocholestane derivatives as anticancer agents.

Mar Drugs 2014 Mar 25;12(4):1715-31. Epub 2014 Mar 25.

Clinical Chemistry Program, Department of Chemistry, SI 424, Cleveland State University, Cleveland, OH 44115, USA.

Using analogues of some marine steroidal oximes as precursors, a series of aza-B-homocholestane derivatives possessing different substituted groups at the 3-position of the steroidal nucleus were synthesized. Their biological activity against cancer cell proliferation was determined with multiple cancer cell lines. Aza-B-homocholestane derivatives possessing 3-hydroxyl, 3-hydroximino and 3-thiosemicarbazone groups displayed remarkable cytotoxicity to cancer cells via apoptosis inducing mechanism. Compounds 5, 10, 12, 15 and 18 exhibited better potency to inhibit cancer cell proliferation. In addition, compound 15 was further evaluated with three dimensional (3D) multicellular spheroids assay to determine its potency against spheroid growth. The structure-activity relationship (SAR) generated in the studies is valuable for the design of novel chemotherapeutic agents.
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http://dx.doi.org/10.3390/md12041715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4012452PMC
March 2014

[Analysis mediating effect of self-efficacy between diet-related cognitive and behavioral].

Wei Sheng Yan Jiu 2014 Jan;43(1):87-91

Department of Public Health, Guiyang Medical University, Guiyang 550004, China.

Objective: To investigate the influence of self-efficacy between diet-related cognitive and behavioral by introducing the concept of mediating effect in children and adolescents.

Methods: Using multistage cluster sampling, 9 middle and primary school at 1 downtown area and 2 county areas in Guizhou province were selected. Referencing to the foreign-related research and design of the questionnaire, 1398 students were included. The general survey and the correlation analysis about the cognition and self-efficacy of related diet, the favorable behavior related health and the unfavorable behavior related health were conducted. Using the regression analysis and building the modeling to test the mediating effect of self-efficacy of related diet.

Results: The average scores of the cognition, self-efficacy and beneficial health's behavior of related diet were not high. There were significant correlation between the cognition and self-efficacy, the cognition and favorable behavior, the self-efficacy and favorable behavior, the favorable behavior and unfavorable behavior. The correlation coefficients were 0.292, 0.248, 0.228 and -0.102 (P < 0.01). The self-efficacy had significant indirect mediating effect between diet-related cognitive and beneficial health's behavior, the indirect mediating effect was 24.52% of the total effect. Bringing into the structural equation model to test, the indirect effect of self-efficacy (namely mediating effect) was more obvious (beta = 0.39, P < 0.01).

Conclusion: In the actual dietary behavior of children and adolescents, improving the self-efficacy can increase the degree of changing in behavior which acted by the cognition.
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January 2014

Synthesis and in vitro antiproliferative evaluation of some novel B-norcholesterols.

Steroids 2014 Jan 5;79:37-43. Epub 2013 Nov 5.

College of Chemistry and Life Science, Guangxi Teachers Education University, Nanning 530001, China. Electronic address:

Some novel B-norcholesterols with different substituted groups were synthesized. The antiproliferative activity of the compounds against cervical carcinoma (HeLa), liver cancer (Bel 7404) and gastric cancer (SGC 7901) cells was assayed. The results revealed that the presence of a 6-alkylthiosemicarbazone or 6-cyano group could enhance the antiproliferative activity of these compounds. The induction of compounds 6 and 9 to cancer cell apoptosis were assayed by flow cytometry, and the results showed that the compounds were able to effectively induce cancer cell apoptosis. The research provided a theoretical reference for the exploration of new anti-cancer drug. The results suggest that compounds 6 and 9 based on its abeo-cholestane may constitute a novel class of antiproliferative agents, which deserve further study.
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http://dx.doi.org/10.1016/j.steroids.2013.10.009DOI Listing
January 2014

Synthesis and cytotoxic activity of some 4,6-diaza-A,B-dihomo-steroid bilactams.

Steroids 2014 Jan 4;79:14-8. Epub 2013 Nov 4.

College of Chemistry and Life Science, Guangxi Teachers Education University, Nanning 530001, PR China. Electronic address:

Using cholesterol, stigmasterol and sitosterol as starting materials, some 4,6-diaza-A,B-dihomo-steroid bilactams were synthesized via two different synthetic routes by oxidation, reduction, oximation, Beckman rearrangement, etc. The cytotoxic activity of the synthesized compounds against SGC 7901 (human ventriculi carcinoma), Bel-7404 (human liver carcinoma), HeLa (human cervical carcinoma) and HT-29 (colonic carcinoma) cancer cells were investigated. The results showed that compounds 2 and 7b displayed a good cytotoxic activity to the SGC 7901, Bel 7404 and HeLa tumor cell lines with the IC50 values of 11.6, 16.4, 13.9 and 13.1, 21.8, 13.1 μmol/L, respectively. Their cytotoxic activity is almost same as cisplatin to these cells. The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.
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http://dx.doi.org/10.1016/j.steroids.2013.10.011DOI Listing
January 2014
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