☆ 4.7 Article

Synthesis and biological evaluation of 1,2-dithiol-3-thiones and pyrrolo[1,2-a]pyrazines as novel hypoxia inducible factor-1 (HIF-1) inhibitor

BIOORGANIC & MEDICINAL CHEMISTRY (2016)

期刊

BIOORGANIC & MEDICINAL CHEMISTRY

卷 24, 期 12, 页码 2843-2851

出版社

PERGAMON-ELSEVIER SCIENCE LTD

DOI: 10.1016/j.bmc.2016.04.054

关键词

Hypoxia inducible factor-1; VEGF; GLUT-1; Oltipraz; Pyrrolopyrazine

类别

Biochemistry & Molecular Biology Chemistry, Medicinal Chemistry, Organic

向作者/读者索取更多资源

Protocol

Reagent

摘要

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor which is strongly associated with tumor survival, progression, and therapeutic resistance. Accordingly, it has been suggested that the inhibition of the HIF-1 pathway can suppress tumor, and it has become an important therapeutic target. In present study, oltipraz, its metabolite M2, and their derivatives were synthesized and evaluated as HIF-1 alpha inhibitors. Among the synthesized, benzyl-substituted pyrrolo[1,2-a]pyrazine 2g most potently inhibited HIF-1 alpha protein accumulation (81% at 10 mu M) and VEGF, GLUT-1 transcription (77% and 92% at 10 mu M, respectively). (C) 2016 Elsevier Ltd. All rights reserved.

作者

我是这篇论文的作者

点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7

评分不足

次要评分

新颖性

-

重要性

-

科学严谨性

-

评价这篇论文

推荐

Review Pharmacology & Pharmacy

Hypoxia-inducible factor-1: Regulatory mechanisms and drug development in stroke

Zirong Pan, Guodong Ma, Linglei Kong, Guanhua Du

Summary: Stroke is an acute cerebrovascular disease caused by sudden rupture or blockage of blood vessels in the brain, and HIF-1 plays an important role in regulating various pathways in the pathological process. The roles of HIF-1 in stroke are controversial, involving factors such as ischemic time and degree, and its regulatory mechanisms include inflammation, autophagy, oxidative stress, and apoptosis.

PHARMACOLOGICAL RESEARCH (2021)

添加到收藏夹

Article Biochemistry & Molecular Biology

Inhibition of hypoxia-inducible factor 1 by acriflavine renders glioblastoma sensitive for photodynamic therapy

Shuai Ma, Fang Wang, Jiawei Dong, Nan Wang, Shengzhong Tao, Jianyang Du, Shaoshan Hu

Summary: This study demonstrates that the combination of photodynamics therapy (PDT) and Aciflavine (ACF) can decrease the expression of HIF1α and regulate the downstream signaling pathways, thereby enhancing the efficacy of PDT in treating recalcitrant glioblastoma (GBM).

JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY (2022)

添加到收藏夹

Article Medicine, Research & Experimental

Licochalcone A inhibits hypoxia-inducible factor-1 α accumulation by suppressing mitochondrial respiration in hypoxic cancer cells

Min Kyung Park, Jun Ji, Keeok Haam, Tae-Hee Han, Seona Lim, Mi-Jung Kang, Soon Sung Lim, Hyun Seung Ban

Summary: Licochalcone A, a component of Glycyrrhiza uralensis, demonstrates potential as a therapeutic agent in hypoxic cancer cells by inhibiting HIF-1 alpha accumulation and mitochondrial respiration, leading to increased oxygen content and suppression of cancer cell viability.

BIOMEDICINE & PHARMACOTHERAPY (2021)

添加到收藏夹

Review Pharmacology & Pharmacy

The role of hypoxia-inducible factors in cardiovascular diseases

Baoqi Yu, Xia Wang, Yanting Song, Guomin Xie, Shiyu Jiao, Li Shi, Xuejie Cao, Xinyao Han, Aijuan Qu

Summary: Cardiovascular diseases are the leading cause of death worldwide, and hypoxia-inducible factors (HIFs) play an important role in their pathogenesis. Recent studies have revealed the role of cell-specific HIFs in various cardiovascular diseases, but the potential clinical application of HIF inhibitors in the treatment of cardiovascular diseases is not well understood.

PHARMACOLOGY & THERAPEUTICS (2022)

添加到收藏夹

Article Biology

Repression of hypoxia-inducible factor-1 contributes to increased mitochondrial reactive oxygen species production in diabetes

Xiaowei Zheng, Sampath Narayanan, Cheng Xu, Sofie Eliasson Angelstig, Jacob Grunler, Allan Zhao, Alessandro Di Toro, Luciano Bernardi, Massimiliano Mazzone, Peter Carmeliet, Marianna Del Sole, Giancarlo Solaini, Elisabete A. Forsberg, Ao Zhang, Kerstin Brismar, Tomas A. Schiffer, Neda Rajamand Ekberg, Ileana Ruxandra Botusan, Fredrik Palm, Sergiu-Bogdan Catrina

Summary: Excessive production of mitochondrial reactive oxygen species (ROS) in diabetes complications is mainly caused by impaired responses to hypoxia due to the inhibition of hypoxia-inducible factor-1 (HIF-1) by hyperglycemia. Restoring HIF-1 function can attenuate ROS overproduction, protect cells against apoptosis and renal injury in diabetes. These findings suggest that targeting HIF-1 repression could be a potential therapeutic strategy for diabetic complications.

ELIFE (2022)

添加到收藏夹

Article Environmental Sciences

Hypoxia inducible factor-1? (HIF-1?) as an early predictor of acute hydrogen cyanamide (Dormex) poisoning

Meriam N. N. Rezk, Gerges M. Beshreda, Dalia Abdelrahman Meshref, Walaa Yehia Abdelzaher, Gaber El-Saber Batiha, Amin A. Hafiz, Duaa Althumairy, Nada H. Aljarba, Nermeen N. Welson

Summary: This study aimed to investigate the role of hypoxiainducible factor-1 alpha (HIF-1 alpha) in the diagnosis, prediction, and follow-up of Dormex-intoxicated patients. The results showed that HIF-1 alpha can effectively predict and follow up patients within 24 hours after admission. Additionally, blood-related indicators were also significantly abnormal in patients with Dormex intoxication.

ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY (2023)

添加到收藏夹

Article Biochemistry & Molecular Biology

Molecular docking and pharmacophore models to probe binding hypothesis of inhibitors of hypoxia inducible factor-1

Zaira Rehman, Ishrat Jabeen, Ammad Fahim, Attya Bhatti, Peter John

Summary: A ligand-based pharmacophore model was developed to identify potential HIF-1α and β dimerization inhibitors, resulting in the identification of six hits with potential anti-cancer chemotherapy activity. These compounds could serve as potential inhibitors of HIF-1 dimerization after further structure optimization.

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS (2022)

添加到收藏夹

Article Toxicology

The role of hypoxia-inducible factor 1 alpha (HIF-1α) modulation in heavy metal toxicity

Michael Aschner, Anatoly V. Skalny, Rongzhu Lu, Abel Santamaria, Ji-Chang Zhou, Tao Ke, Mikhail Yu. Karganov, Aristides Tsatsakis, Kirill S. Golokhvast, Aaron B. Bowman, Alexey A. Tinkov

Summary: This review summarizes the existing data on the effects of toxic metals on HIF-1 signaling and its underlying mechanisms, with a special focus on the prooxidant effect of metals. The effect of metals on HIF-1 pathway varies depending on the cell type, ranging from down-regulation to up-regulation. Inhibition of HIF-1 signaling may contribute to hypoxic damage in cells, while metal-induced activation may promote tumor growth and contribute to the carcinogenic effects of heavy metals.

ARCHIVES OF TOXICOLOGY (2023)

添加到收藏夹

Article Biochemistry & Molecular Biology

Exploiting the Role of Hypoxia-Inducible Factor 1 and Pseudohypoxia in the Myelodysplastic Syndrome Pathophysiology

Ioanna E. Stergiou, Konstantinos Kambas, Aikaterini Poulaki, Stavroula Giannouli, Theodora Katsila, Aglaia Dimitrakopoulou, Veroniki Vidali, Vasileios Mouchtouris, Ismini Kloukina, Evangelia Xingi, Stamatis N. Pagakis, Lesley Probert, George P. Patrinos, Konstantinos Ritis, Athanasios G. Tzioufas, Michael Voulgarelis

Summary: Myelodysplastic syndromes (MDS) involve a group of disorders affecting hematopoietic stem and progenitor cells, with a particular focus on the role of the transcription factor HIF-1. Aberrant HIF-1 stabilization and pseudohypoxia are prominent features in MDS pathobiology, showing potential for therapeutic manipulation in benign cases.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

添加到收藏夹

Article Biochemistry & Molecular Biology

Conditional Knockout of Hypoxia-Inducible Factor 1-Alpha in Tumor-Infiltrating Neutrophils Protects against Pancreatic Ductal Adenocarcinoma

Je Lin Sieow, Hweixian Leong Penny, Sin Yee Gun, Ling Qiao Tan, Kaibo Duan, Joe Poh Sheng Yeong, Angela Pang, Diana Lim, Han Chong Toh, Tony Kiat Hon Lim, Edgar Engleman, Olaf Rotzschke, Lai Guan Ng, Jinmao Chen, Suet Mien Tan, Siew Cheng Wong

Summary: A large number of neutrophils infiltrate tumors and contribute to the inflammatory tumor microenvironment. The metabolic status of these neutrophils and their role in tumor progression were investigated in a mouse model of pancreatic ductal adenocarcinoma (PDAC). Tumor-infiltrating neutrophils showed enhanced glycolytic activity compared to neutrophils from the bone marrow and blood of the same mouse. Deletion of hypoxia-inducible factor 1-alpha (HIF-1 alpha) in neutrophils reduced tumor burden and improved survival in the mouse model, indicating a potential target for metabolic modulation in cancer.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

添加到收藏夹

Article Biology

Aquatic surface respiration improves survival during hypoxia in zebrafish (Danio rerio) lacking hypoxia-inducible factor 1-α

Milica Mandic, Kaitlyn Flear, Pearl Qiu, Yihang K. Pan, Steve F. Perry, Kathleen M. Gilmour

Summary: HIF-1α is important for hypoxic survival in zebrafish, particularly in relation to their ability to perform aquatic surface respiration (ASR). When zebrafish are prevented from accessing the surface during severe hypoxia, their survival is significantly compromised. However, when they are allowed to access the surface, there is no difference in survival between wild-type and HIF-1α knockout fish. ASR mitigates the negative effects of HIF-1α loss, with knockouts initiating ASR at a higher oxygen concentration and performing ASR for longer than wild-types.

PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES (2022)

添加到收藏夹

Article Immunology

Alcohol-Induced Glycolytic Shift in Alveolar Macrophages Is Mediated by Hypoxia-Inducible Factor-1 Alpha

Niya L. Morris, David N. Michael, Kathryn M. Crotty, Sarah S. Chang, Samantha M. Yeligar

Summary: This study investigated the effects of alcohol on the metabolism of alveolar macrophages, revealing that chronic alcohol exposure leads to a shift towards glycolysis in alveolar macrophages, resulting in reduced phagocytic capacity.

FRONTIERS IN IMMUNOLOGY (2022)

添加到收藏夹

Article Immunology

Hypoxia inducible-factor 1 alpha regulates neutrophil recruitment during fungal-elicited granulomatous inflammation

Sara da Silva-Ferreira, Claudio Duarte-Oliveira, Daniela Antunes, Catarina Barbosa-Matos, Ana Mendes-Frias, Egidio Torrado, Sandra Costa, Ricardo Silvestre, Cristina Cunha, Agostinho Carvalho

Summary: Chronic pulmonary aspergillosis is a devastating disease with increasing prevalence worldwide. The characteristic inflammation limits the effectiveness of antifungal therapies. The study shows that hypoxia-inducible factor 1 alpha (HIF-1 alpha) plays a central role in regulating neutrophil function and fungal infection.

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY (2022)

添加到收藏夹

Article Cardiac & Cardiovascular Systems

Myeloid hypoxia-inducible factor HIF1A provides cardio-protection during ischemia and reperfusion via induction of netrin-1

Ka Lin Heck-Swain, Jiwen Li, Wei Ruan, Xiaoyi Yuan, Yanyu Wang, Michael Koeppen, Holger K. Eltzschig

Summary: The myeloid-expressed HIF1A plays a functional role in providing cardioprotection during ischemia and reperfusion injury by inducing the neuronal guidance molecule netrin-1 in neutrophils.

FRONTIERS IN CARDIOVASCULAR MEDICINE (2022)

添加到收藏夹

Article Oncology

LncIHAT Is Induced by Hypoxia-Inducible Factor 1 and Promotes Breast Cancer Progression

Lin Chen, Lei Bao, Yanling Niu, Jennifer E. Wang, Ashwani Kumar, Chao Xing, Yingfei Wang, Weibo Luo

Summary: This study identified a hypoxia-induced oncogenic lncRNA, named lncIHAT, which promoted survival, tumor growth, and lung metastasis of TNBC cells by regulating the expression of oncogenic genes PDK1 and ITGA6.

MOLECULAR CANCER RESEARCH (2021)

添加到收藏夹

Article Biochemistry & Molecular Biology

Potential Functional Role of Phenethylamine Derivatives in Inhibiting Dopamine Reuptake: Structure-Activity Relationship

Dooti Kundu, Anlin Zhu, Eunae Kim, Suresh Paudel, Choon-Gon Jang, Yong Sup Lee, Kyeong-Man Kim

Summary: This study investigated the structure-activity relationship of 29 6-phenethylamine derivatives in their ability to inhibit dopamine reuptake. The researchers found that different substituents and alkyl groups had varying effects on the inhibitory activity, and identified the stability and binding abilities of two selected compounds. The study also revealed the functional role of dopamine reuptake inhibitors in regulating dopamine D2 receptor function.

BIOMOLECULES & THERAPEUTICS (2022)

添加到收藏夹

Article Biochemistry & Molecular Biology

Structure-Activity Relationship and Evaluation of Phenethylamine and Tryptamine Derivatives for Affinity towards 5-Hydroxytryptamine Type 2A Receptor

Shujie Wang, Anlin Zhu, Suresh Paudel, Choon-Gon Jang, Yong Sup Lee, Kyeong-Man Kim

Summary: The structure-activity relationship (SAR) of phenethylamine and tryptamine derivatives for binding 5-HT2AR was determined and functional and regulatory evaluation of selected compounds was conducted. Phenethylamines showed higher affinity to 5-HT2AR than tryptamines, with alkyl or halogen groups on the phenyl ring exerting positive effects on binding affinity in phenethylamines. Oxygen-containing groups on R-3 of phenethylamines had mixed influences. Oxygen-containing substituents on the large ring and alkyl substituents on the small ring of tryptamine groups had positive and negative influences, respectively.

BIOMOLECULES & THERAPEUTICS (2023)

添加到收藏夹

Article Chemistry, Medicinal

Design, Rational Repurposing, Synthesis, In Vitro Evaluation, Homology Modeling and In Silico Study of Sulfuretin Analogs as Potential Antileishmanial Hit Compounds

Ahmed H. E. Hassan, Trong-Nhat Phan, Yeonwoo Choi, Suyeon Moon, Joo Hwan No, Yong Sup Lee

Summary: This study developed sulfuretin analogs that have the potential to inhibit the immunosuppressive PGE(2) and directly inhibit the growth of Leishmania donovani. Among the library of analogs, compounds 1i and 1q showed the most promising activity. Cytotoxicity evaluation demonstrated that compound 1i specifically targets the parasite without affecting host cells. In silico simulation provided insights into the binding between these analogs and Leishmania donovani fumarate reductase. These findings suggest that compounds 1i and 1q could be further developed as multifunctional therapeutic agents against visceral leishmaniasis.

PHARMACEUTICALS (2022)

添加到收藏夹

Article Toxicology

Mepirapim, a novel synthetic cannabinoid, induces Parkinson's disease-related behaviors by causing maladaptation of the dopamine system in the brain

Kwang-Hyun Hur, Youyoung Lee, Audrey Lynn Donio, Jae-Gyeong Lee, Bo-Ram Lee, Seon-Kyung Kim, Seolmin Yoon, Yong-Sup Lee, Hyoung-Chun Kim, Seok-Yong Lee, Choon-Gon Jang

Summary: This study investigated the neurotoxic effects of Mepirapim and found that it causes Parkinson's disease-related symptoms and maladaptation of the dopamine system in mice.

ARCHIVES OF TOXICOLOGY (2023)

添加到收藏夹

Article Biochemistry & Molecular Biology

Protective effect of 7-hydroxyl-1-methylindole-3-acetonitrile on the intestinal mucosal damage response to inflammation in mice with DSS-induced colitis

Kyung-Sook Chung, Sang-Eun Park, Jung-Hun Lee, Su-Yeon Kim, Hee-Soo Han, Yong Sup Lee, Seang-Hwan Jung, Eungyeong Jang, Sangmin Lee, Kyung-Tae Lee

Summary: In this study, 7-HMIA was found to decrease the severity of colitis by protecting the inflamed mucosal barrier through inhibiting the activation of NF-Kappa B and STAT3.

CHEMICO-BIOLOGICAL INTERACTIONS (2023)

添加到收藏夹

Article Chemistry, Medicinal

Design, synthesis, and repurposing of O6-aminoalkyl-sulfuretin analogs towards discovery of potential lead compounds as antileishmanial agents

Ahmed H. E. Hassan, Trong-Nhat Phan, Suyeon Moon, Chae Hyeon Lee, Yeon Ju Kim, Soo Bin Cho, Selwan M. El-Sayed, Yeonwoo Choi, Joo Hwan No, Yong Sup Lee

Summary: A potential lead compound, 2o, was identified in this study for the treatment of visceral leishmaniasis. It showed promising activity against the parasite Leishmania donovani and had an acceptable safety profile. This research provides a starting point for the development of new drugs for the treatment of this neglected tropical disease.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2023)

添加到收藏夹

Article Chemistry, Medicinal

Bestatin analogs-4-quinolinone hybrids as antileishmanial hits: Design, repurposing rational, synthesis, in vitro and in silico studies

Ahmed H. E. Hassan, Kazem Mahmoud, Trong-Nhat Phan, Moataz A. Shaldam, Chae Hyeon Lee, Yeon Ju Kim, Soo Bin Cho, Waleed A. Bayoumi, Selwan M. El-Sayed, Yeonwoo Choi, Suyeon Moon, Joo Hwan No, Yong Sup Lee

Summary: Visceral leishmaniasis caused by L. donovani is highly fatal, and the discovery of new hit compounds can lead to the development of novel therapeutics. A small library of bestatin analogs-4-quinolone hybrids was designed and evaluated, revealing distinct profiles for different types of hybrids. Hybrid 1e and hybrid 2j were identified as potential hits that inhibit the growth of L. donovani promastigotes, and they showed excellent safety profiles in comparison to the drug erufosine. In silico studies and molecular dynamics simulations provided insights into the binding mode and impact of hybrid 1e on LdMetAP-1 and LdMetAP-2.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2023)

添加到收藏夹

Article Biochemistry & Molecular Biology

Design, synthesis, and study of novel phenethyl-based antitumor phospholipids downregulating p38 mitogen-activated protein kinase

Ahmed H. E. Hassan, Yeon Il Oh, Chae Hyeon Lee, Yeon Ju Kim, Soo Bin Cho, Md. Maqusood Alam, Sang-Eun Park, Kyung-Sook Chung, Kyung-Tae Lee, Yong Sup Lee

Summary: Phenethyl-based edelfosine-analogs with different alkoxy substituents on the phenyl ring were designed as antitumor lipids modulating p38 MAPK activity. Saturated and monounsaturated alkoxy-substituted derivatives showed the highest antitumor activity against various cancer cells. Ortho-substituted compounds were more active than meta- or ortho-substituted compounds. Compound 1b emerged as the most potent inhibitor of p38 MAPK activity. In silico study suggested that compounds 1b and 1a could potentially bind to the lipid binding pocket of p38 MAPK. Overall, compounds 1b and 1a have broad spectrum antitumor potential through p38 MAPK modulation.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY (2023)

添加到收藏夹

Article Pharmacology & Pharmacy

Deletion of Cryab increases the vulnerability of mice to the addiction-like effects of the cannabinoid JWH-018 via upregulation of striatal NF-?B expression

Leandro Val Sayson, Darlene Mae Ortiz, Hyun Jun Lee, Mikyung Kim, Raly James Perez Custodio, Jaesuk Yun, Chae Hyeon Lee, Yong Sup Lee, Hye Jin Cha, Jae Hoon Cheong, Hee Jin Kim

Summary: Recent findings suggest that Cryab knockout mice may serve as a potential animal model for studying the addictive effects of synthetic cannabinoids.

FRONTIERS IN PHARMACOLOGY (2023)

添加到收藏夹

Article Biochemistry & Molecular Biology

Synthesis and Biological Evaluation of O6-Aminoalkyl-Hispidol Analogs as Multifunctional Monoamine Oxidase-B Inhibitors towards Management of Neurodegenerative Diseases

Ahmed H. E. Hassan, Hyeon Jeong Kim, Keontae Park, Yeonwoo Choi, Suyeon Moon, Chae Hyeon Lee, Yeon Ju Kim, Soo Bin Cho, Min Sung Gee, Danbi Lee, Jong-Hyun Park, Jong Kil Lee, Jong Hoon Ryu, Ki Duk Park, Yong Sup Lee

Summary: This study aims to develop a multifunctional agent that inhibits the production of reactive oxygen species by monoamine oxidases, lowers neurodegeneration, and inhibits acetylcholinesterase and neuroinflammation. Compounds 3aa and 3bc were identified as potential multifunctional molecules with selective MAO-B inhibition, AChE inhibition, and the inhibition of microglial PGE(2) production. Compound 3bc showed comparable activity to donepezil in improving memory and cognitive impairments.

ANTIOXIDANTS (2023)

添加到收藏夹

Article Chemistry, Medicinal

Design, synthesis, and evaluation of new anti-inflammatory natural products amide derivatives endowed with anti-blood cancer activity towards development of potential multifunctional agents against hematological cancers

Ahmed H. E. Hassan, Hye Jin Kim, Su Jin Jung, Seo-Yun Jang, Selwan M. El-Sayed, Kyung-Tae Lee, Yong Sup Lee

Summary: New amide derivatives of the natural product 5,6,7-trimethoxyflavanone were designed and synthesized for their potential antiproliferative effects against blood cancer and inflammation. Compound 2v showed the most promising inhibitory effects on the production of proinflammatory mediators and exhibited significantly higher potency against diverse blood cancers compared to the standard drug imatinib. Moreover, compound 2v showed selectivity towards blood cancer cells and induced apoptosis in HL60 leukemia cells.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2023)

添加到收藏夹

Article Chemistry, Medicinal

Scaffold hopping of N-benzyl-3,4,5-trimethoxyaniline: 5,6,7-Trimethoxy- flavan derivatives as novel potential anticancer agents modulating hippo signaling pathway

Ahmed H. E. Hassan, Cai Yi Wang, Hyo Jong Lee, Su Jin Jung, Yeon Ju Kim, Soo Bin Cho, Chae Hyeon Lee, Gyeongpyo Ham, Taegeun Oh, Sang Kook Lee, Yong Sup Lee

Summary: Scaffold hopping of N-benzyl-3,4,5-trimethoxyaniline yielded 5,6,7-trimethoxyflavan derivatives synthesized in four linear steps. Compounds 8q and 8e showed interesting activity against a panel of cancer cells. Compound 8q displayed comparable potencies to gefitinib and oxaliplatin against lung and colorectal cancers, and superior potencies to several other drugs against various cancers. In addition, it induced apoptosis, triggered cell cycle arrest, and activated hippo signaling while inhibiting the PI3k pathway. Compound 8q shows potential as a lead compound for further development of anticancer agents.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2023)

添加到收藏夹

Article Clinical Neurology

The differential vulnerabilities of Per2 knockout mice to the addictive properties of methamphetamine and cocaine

Leandro Val Sayson, Hyun Jun Lee, Darlene Mae Ortiz, Mikyung Kim, Raly James Perez Custodio, Chae Hyeon Lee, Yong Sup Lee, Jae Hoon Cheong, Hee Jin Kim

Summary: Using Per2 knockout mice, it was found that these mice showed increased addiction-like responses to METH and 5-EAPB, but similar responses to COC and dimethocaine compared to wild-type mice, suggesting a divergent influence of Per2 deficiency on susceptibility to specific psychostimulants.

PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY (2023)

添加到收藏夹

Article Food Science & Technology

Chemical transformation of cannabidiol into psychotropic cannabinoids under acidic reaction conditions: Identifiication of transformed products by GC-MS

Minsun Jeong, Sangin Lee, Chaeyoung Seo, Eunjeong Kwon, Soohyang Rho, Mansoo Cho, Moon Yeon Kim, Wonwoong Lee, Yong Sup Lee, Jongki Hong

Summary: Recently, the focus in the cannabis industry has been on cannabidiol (CBD), which has various pharmacological effects. It has been found that CBD can convert into psychoactive cannabinoids, such as D9-THC, under acidic conditions. In this study, the transformation of CBD was examined at different pH levels and temperatures. Several transformed products were identified, including major components like D9-THC and minor components like THC isomers. The study provides important insights into the control of CBD manufacturing processes and the regulation of its industrial applications.

JOURNAL OF FOOD AND DRUG ANALYSIS (2023)

添加到收藏夹

Article Chemistry, Medicinal

Repurposing Synthetic Congeners of a Natural Product Aurone Unveils a Lead Antitumor Agent Inhibiting Folded P-Loop Conformation of MET Receptor Tyrosine Kinase

Ahmed H. E. Hassan, Cai Yi Wang, Cheol Jung Lee, Hye Rim Jeon, Yeonwoo Choi, Suyeon Moon, Chae Hyeon Lee, Yeon Ju Kim, Soo Bin Cho, Kazem Mahmoud, Selwan M. El-Sayed, Sang Kook Lee, Yong Sup Lee

Summary: A library of sulfuretin congeners was evaluated for their anticancer activities against nine cancer diseases, and congener 1t was identified as a potential compound that can inhibit the growth of colon cancer cells. Mechanistic studies showed that congener 1t induced cell cycle arrest and apoptosis in colon cancer cells by regulating protein levels and targeting the MET receptor tyrosine kinase. In silico study further supported the binding of congener 1t to the MET receptor tyrosine kinase. Overall, this study suggests that congener 1t is an interesting lead compound for further development as an anticancer agent.

PHARMACEUTICALS (2023)

添加到收藏夹

暂无数据

© Peeref 2019-2024. All rights reserved.