CRYSTENGCOMM
·
2022
·Vol. 24
·期 35
·6165-6171
·
IF 3.756
Xinghui Hao,Jinhui Li,Chenguang Wang,Xinghua Zhao,Xin He,Changquan Calvin Sun
Dimetronidazole (DMZ), an veterinary antibiotic, exhibits poor photostability with only 80.38% potency remaining after exposure to illuminance of 4500 lux for 7 days. The photodegradation is accompanied by obvious color change. A 1 : 1 cocrystal of DMZ with saccharine exhibited profoundly improved photostability with 98.95% of DMZ remaining after 7 days under the same light exposure. Thus, this new cocrystal can be used to develop more stable drug products of DMZ.
研究领域:
药学
·
化学
✓ 已验证
DOI
高影响因子
CRYSTAL GROWTH & DESIGN
·
2020
·
IF 4.089
Dingyan Wang,Zeen Yang,Bingqing Zhu,Xuefeng Mei,Xiaomin Luo
A machine-learning model trained on the whole Cambridge Structural Database was developed to assist high-throughput cocrystal screening. With only 2D structures taken as inputs, the probability of cocrystal formation is returned for two given molecules. All of the cocrystal records in the CSD were used as positive samples, while negative samples were constructed by randomly combining different molecules into chemical pairs. Our model showed a prediction ability comparable with that of a widely used ab initio method in a head-to-head comparison test. Both experimental and virtual cocrystal screening against captopril were conducted at the same time to further validate the model. Two cocrystals of captopril with l-proline and sarcosine were obtained and characterized by PXRD, DSC, and FT-IR. These two coformers were also successfully predicted by our model. These results suggest that the tool we developed can be used to effectively guide coformer selection in the discovery of new cocrystals.
研究领域:
化学信息学
·
材料科学
·
药物化学
✓ 已验证
DOI
高影响因子
Cell Reports Physical Science
·
2025
·
IF 7.3
Yan-Wei Jiang,Zhong-Wei Zhang,Chi Wai Cheung,Jun-An Ma
Trifluoromethyl ketones (TFMKs) represent a crucial class of functional groups in organic synthesis and drug design. Carbo- and heteroatom-substituted methyl TFMKs have been developed extensively, leading to a broad array of structurally diverse trifluoromethylated compounds. However, aminomethyl TFMKs remain largely underexplored, likely due to the intrinsic incompatibility between amino and carbonyl groups. Here, we present a modular strategy for accessing aminomethyl TFMKs in a cyclic acetal-protected form. Using 2-(trifluoromethyl)-1,3-dioxolane-2-carboxylic acid as a masked trifluoroacetyl radical precursor, along with nitroarenes and tertiary alkylamines as readily available reaction components, we demonstrate the feasibility of assembling these compounds under metallaphotocatalytic conditions. This approach selectively yields a diverse array of N -(2-trifluoromethyl)dioxolanylmethyl aniline compounds, which act as inactivated forms of arylaminomethyl TFMKs and can be readily converted into arylaminomethyl TFMKs, various amine derivatives, and azaheterocycles. The structurally distinctive trifluoromethylated dioxolanylmethyl anilines and their downstream products hold significant potential for pharmaceutical and agrochemical development.
研究领域:
有机化学
·
药物化学
·
合成化学
✓ 已验证
DOI
高影响因子
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
·
2013
·
IF 2.206
Chongjun Liu,Leping Dang,Wenshuai Bai,Hongyuan Wei
The water activity aT[H2O] that corresponds to the transformation between hydrate and anhydrate forms of a drug is important to pharmaceutical process development; however, the traditional method for measuring aT[H2O] can be time-consuming. A thermodynamic model derived from the thermodynamic equilibrium in this study provides an easy way to predict the value of aT[H2O] at different temperatures through the solubility ratio of hydrate to anhydrate. The model also provides a new way to determine the solubility of the metastable form with accessible accuracy and offers a tool to study the activity coefficient of the solute. Experimental validation of the model was performed using the compounds theophylline and carbamazepine. The results illustrate that this new method is acceptably accurate and reproducible.
研究领域:
药学
·
物理化学
✓ 已验证
DOI
高影响因子
Frontiers in Microbiology
·
2024
·
IF 4
Qian Jiali,Li Zhennan,Wang Jinhui,Lin Yuxian,Yu Yingcong
The resistance of Helicobacter pylori (H. pylori) has increased in recent years, prompting a trend in the research and development of new drugs. In our study, three derivatives (JF-1, JF-2, and JF-3) were synthesized using 6-gingerol as the main component, while JF-4, containing both 6-gingerol and 6-shogaol as the main components, was extracted from dried ginger. The minimum inhibitory concentrations (MICs), determined using the ratio dilution method, were 80 μg/mL for JF-1, 40 μg/mL for JF-2, 30 μg/mL for JF-3, 40 μg/mL for JF-4, 60 μg/mL for 6-gingerol standard (SS), and 0.03 μg/mL for amoxicillin (AMX). After treating H. pylori-infected mice, the inflammation of the gastric mucosa was suppressed. The eradication rate of H. pylori was 16.7% of JF-3 low-dose treatment (LDT), 25.0% of JF-3 high-dose treatment (HDT), 16.7% of JF-4 LDT, 16.7% of JF-4 HDT, 30% of SS LDT, 50% of SS HDT, and 36.4% of the positive control group (PCG). The levels of gastrin, somatostatin (SST), IFN-γ, IL-4, and IL-8 were significantly recovered in the JF-3 and JF-4 administration groups, but the effect was stronger in the high-dose group. These results demonstrate that 6-gingerol and its derivatives have significant anti-Helicobacter pylori effects and are promising potential treatments for H. pylori infection.
研究领域:
药理学
·
微生物学
·
胃肠病学
·
化学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Fei Cai,Jinrong Dong,Peng Xie,Hanlong He,Huiyi Yao,Junxian Guo,Zhibo Yan,Li Ma,Tianfeng Chen
Developing structurally well-defined targeted drugs is an effective way to enhance the chemotherapy efficacy. Herein, a target mitochondrial complex I (complex I) inhibitor was developed for the key methylation site ARG-85 in the key subunit NDUFS2. Based on the unique :NH═C– group of guanidyl and the surrounding environment of ARG-85, the macrocyclic and bulky manganese porphyrin complex [MnIII(TTPPC2–)]+ was selected to insert into the gap of NDUFS2. Experimental and computational analyses revealed that the planar π system of the TTPPC2– ligand and the rotatable benzene ring stably bind between the :NH═C– group of ARG-85 and the manganese metal center, a medium-strong Lewis acid. The Mn-specific recognition of guanidine drives the selective inhibition of complex I activity. Further, MnIII(TTPPC2–)]+ was modified into targeted nanoformulation Mn NPs. In vitro and in vivo experiments confirmed the efficient and mechanism inhibition of complex I activity, offering a novel strategy for targeted drug development.
研究领域:
生物化学
·
药物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
iScience
·
2023
·
IF 5.8
Xiao Qi,Zihao Li,Jinrui Zhang,Hongru Li,Guangxin Zhang,Meng Li,Baofeng Li,Yilin Fu,Mingjun Cai,Hongda Wang,Ti Tong,Jing Gao
CDCP1 is a transmembrane protein that is involved in a variety of important biological processes and upregulated in a variety of human solid malignancies; however, its spatial distribution and variation at the molecular level remain unclear. To solve this problem, we first analyzed its expression level and prognostic implications in lung cancer. Then, we used super-resolution microscopy to reveal the spatial organization of CDCP1 at different levels, and found that cancer cells generated more and larger CDCP1 clusters than normal cells. Furthermore, we found that CDCP1 can be integrated into larger and denser clusters as functional domains upon activation. Our findings elucidated the significant differences of CDCP1 clustering characteristics between cancer and normal cells, and revealed the relationship between its distribution and function, which will contribute to a comprehensive understanding of its oncogenic mechanism, and will be of great help for the development of CDCP1-targeted drugs for lung cancer.
研究领域:
肿瘤学
·
细胞生物学
·
分子生物学
·
成像科学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Tissue Engineering
·
2025
·
IF 7
Yue Ma,Runbang He,Bo Deng,Miaomiao Luo,Wenjie Zhang,Lina Mao,Wenxiang Hu,Yilei Mao,Huayu Yang,Pengyu Huang
The development of advanced in vitro models for assessing liver toxicity and drug responses is crucial for personalized medicine and preclinical drug development. 3D bioprinting technology provides opportunities to create human liver models that are suitable for conducting high-throughput screening for liver toxicity. In this study, we fabricated a humanized liver model using human-induced hepatocytes (hiHeps) derived from human fibroblasts via a rapid and efficient reprogramming process. These hiHeps were then employed in 3D bioprinted liver models with bioink materials that closely mimic the natural extracellular matrix. The constructed humanized 3D bioprinted livers (h3DPLs) exhibited mature hepatocyte functions, including albumin expression, glycogen storage, and uptake/release of indocyanine green and acetylated low-density lipoprotein. Notably, h3DPLs demonstrated increased sensitivity to hepatotoxic agents such as acetaminophen (APAP), making them a promising platform for studying drug-induced liver injury. Furthermore, our model accurately reflected the impact of rifampin, a cytochrome P450 inducer, on CYP2E1 levels and APAP hepatotoxicity. These results highlight the potential of hiHep-based h3DPLs as a cost-effective and high-performance alternative for personalized liver toxicity screening and preclinical drug testing, paving the way for improved drug development strategies and personalized therapeutic interventions.
研究领域:
生物医学工程
·
毒理学
·
药理学
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2025
·
IF 8.4
Chen Wen,Shi Kun,Mo Dong,Pan Meng,Bei Zhong-wu,Deng Han-zhi,Yang Pei-pei,Tong Qi,Yuan Li-ping,Wan Yi-yao,Liu Jia-feng,Pan Li-li,Qian Zhi-yong
Mid-low rectal cancer is one of the most common types of rectal cancer and has a poor prognosis. Surgery and chemoradiotherapy are the main treatments for early and advanced rectal cancer with an overall 5-year relative survival rate of only 56.9%. Development of novel antitumor agents is needed. Animal models of disease are indispensable for drug development. The most commonly used animal models of rectal cancer are established by inducing tumors by the subcutaneous transplantation, cecum or peritoneal injection, but not injection in the rectum. Their tumor microenvironment differs from that of rectal tumors in situ, which is hard to precisely simulate the occurrence and development process and drug response of human rectal cancer. In this study, we established orthotopic mouse models of mid-low rectal cancer with primary tumors originating from the rectum, including two models that could simulate the early and advanced stages of the disease, respectively. In the first model, the local primary tumor was restricted to the rectal area of the anal verge by rectal submucosal injection, its growth could be monitored with IVIS live imaging and magnetic resonance imaging. Histological analysis confirmed that the tumor originated from the submucosal layer and then invaded the muscular layer without metastatic tumors. This model may be useful for evaluating drugs for early mid-low rectal cancer in the future. The second model featuring a rectal primary tumor accompanied with abdominal metastases was established via rectal serosal injection. In this model, a large tumor formed at the rectal injection site and then metastasized to the abdominal cavity, reproducing the process from occurrence to metastasis of mid-low rectal cancer, and may be a good tool for the evaluation of drugs for advanced-stage disease. The injection methods used in these models do not require the aid of special colonoscopes, are simple and easy to operate, and have high tumor tumorigenicity and reproducibility. These results suggest that our staged modeling can provide targeted choices for preclinical drug research of mid-low rectal cancer at different stages.
研究领域:
肿瘤学
·
分子生物学
·
药理学
·
医学影像学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Qi Wu,Xue-li Ge,Zi-kai Geng,Hao Wu,Jing-yi Yang,Shi-rong Cao,Ai-lin Yang
HuaChanSu is active water extracts from the skin of Bufo bufo gargarizans Cantor. It has been already used to treat clinical cancers including HCC (Hepatocellular carcinoma, HCC), however, the molecular mechanisms under HuaChanSu's anti-cancer effects remain unclear. PPP (Pentose phosphate pathway, PPP), the major source of ribose and NADPH (Nicotinamide adenine dinucleotide phosphate, NADPH), is always over-activated and particularly critical for tumor cells growth. In this study, firstly, we illustrate that HuaChanSu restrains the growth of human hepatoma cells. More importantly, we demonstrate that the expression of G6PD (Glucose-6-phosphate dehydrogenase, G6PD), the first rate-limiting enzyme of the PPP, is restrained in human hepatoma cells after treatment with HuaChanSu. Additionally, our results show that G6PD enzyme activity and dimer formation are inhibited by HuaChanSu. Furthermore, we find that HuaChanSu could inhibit NADPH production and nucleotide level. In addition, we identify that expression of PLK1 (Polo-like kinase 1, PLK1) is also reduced in response to HuaChanSu, and knockdown of PLK1 restrains enzyme activity and dimer formation of G6PD, but has no effect on G6PD protein level. Subsequently, we demonstrate that inhibition of G6PD could restrain the proliferation of tumor cells and enhance the inhibitory effect of HuaChanSu on cell proliferation of human hepatoma cells. In conclusion, for the first time, our study reveals that HuaChanSu interferes with PPP via suppression of G6PD expression and enzyme activity to restrain growth of tumor cells, and these results provide a novel insight for the anti-hepatoma mechanisms of HuaChanSu and promote the innovation of the research model of TCM. Moreover, the development of drugs targeting abnormal tumor metabolism is currently a hot topic, our works provide theoretical support for further drug development from HuaChanSu, meanwhile, the revelation of the new molecular mechanism also provides a new perspective for the study of the pathogenesis of liver cancer.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
癌症代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Mengxu Sun,Qianying Zhou,Jing Peng,Simin Liu,Jiaxin Luo,Lingling Bai,Wen-Jun Duan,Jin-Xiang Chen,Zong Dai,Jun Chen
As an important disease biomarker, the development of sensitive detection strategies for miRNA, especially intracellular miRNA imaging strategies, is helpful for early diagnosis of diseases, pathological research, and drug development. Hybridization chain reaction (HCR) is widely used for miRNA imaging analysis because of its high specificity and lack of biological enzymes. However, the classic HCR reaction exhibits linear amplification with low efficiency, limiting its use for the rapid analysis of trace miRNA in living cells. To address this problem, we proposed a toehold-mediated exponential HCR (TEHCR) to achieve highly sensitive and efficient imaging of miRNA in living cells using β-FeOOH nanoparticles as transfection vectors. The detection limit of TEHCR was as low as 92.7 fM, which was 8.8 × 103 times lower compared to traditional HCR, and it can effectively distinguish single-base mismatch with high specificity. The TEHCR can also effectively distinguish the different expression levels of miRNA in cancer cells and normal cells. Furthermore, TEHCR can be used to construct OR logic gates for dual miRNA analysis without the need for additional probes, demonstrating high flexibility. This method is expected to play an important role in clinical miRNA-related disease diagnosis and drug development as well as to promote the development of logic gates.
研究领域:
生物技术
·
纳米技术
·
分子生物学
·
癌症研究
·
诊断学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6
Xuwen Chen,Zhengli Luo,Zongjing Hu,Donghui Sun,YingYing He,Jiani Lu,Lili Chen,Shunying Liu
Chemotherapy combining with surgical treatment has been the main strategy for osteosarcoma treatment in clinical. Due to unclear pathogenesis and unidentified drug targets, significant progress has not been made in the development of targeted drugs for osteosarcoma during the past 50 years. Our previous discovery reported compound R - 8i with a high potency for the treatment of osteosarcoma by phenotypic screening. However, both the metabolic stability and bioavailability of R - 8i are poor (T 1/2 = 5.36 min, mouse liver microsome; and bioavailability in vivo F = 52.1 %, intraperitoneal administration) which limits it use for further drug development. Here, we described an extensive structure−activity relationship study of thiazolidine-4-one sulfone inhibitors from R - 8i , which led to the discovery of compound 68 . Compound 68 had a potent cellular activity with an IC 50 value of 0.217 μM, much higher half-life (T 1/2 = 73.8 min, mouse liver microsome) and an excellent pharmacokinetic profile ( in vivo bioavailability F = 115 %, intraperitoneal administration). Compound 68 also showed good antitumor effects and low toxicity in a xenograft model (44.6 % inhibition osteosarcoma growth in BALB/c mice). These results suggest that compound 68 is a potential drug candidate for the treatment of osteosarcoma.
研究领域:
肿瘤学
·
药理学
·
药物发现
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）