Article
Chemistry, Physical
Qiushuang Gao, Peng Yao, Ying Wang, Qizheng Yao, Ji Zhang
Summary: In this study, in silico simulations and drug repurposing approaches were used to identify promising HDAC2 inhibitors. Compounds DB08464, DB00731, DB13930, and DB13696 showed stable binding to HDAC2 and favorable interactions. Additionally, one of the screened compounds, the antiviral drug DB13696, exhibited significant anti-proliferative activity on HepG2 cells with high HDAC2 expression.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Biochemistry & Molecular Biology
Yafeng Tian, Mi Zhang, Panpan Heng, Hua Hou, Baoshan Wang
Summary: As a downstream component, ERK is responsible for phosphorylating substrates in cell proliferation and survival. Inhibiting the MAPK pathway by directly targeting ERK proteins has shown to effectively block tumor growth. A computer-aided drug design approach was used to discover potential ERK inhibitors and reveal their characteristics and mechanisms of action. Through virtual screening, molecular docking, and simulations, two potential inhibitors, VS01 and VS02, were identified. These inhibitors showed stronger binding free energies to ERK compared to the clinic Ulixertinib due to hydrogen bonding, electrostatic, and hydrophilic interactions. These theoretical investigations provide insights for the rational design of ERK inhibitors and future experimental tests.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Andres Felipe Vasquez, Luis Alberto Gomez, Andres Gonzalez Barrios, Diego M. Riano-Pachon
Summary: Antifolates like methotrexate block nucleic acid synthesis and cell proliferation, but their classical structure is ineffective against melanoma. A study combining virtual screening and cell-based assays identified promising non-classical hDHFR inhibitors, with compounds C1 and C2 exhibiting activity against melanoma cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Physical
Prayaga Rajappan Krishnendu, Sonu Benny, Sunil Kumar, Jayalakshmi Jayan, Vaishnav Bhaskar, Leena. K. Pappachen, T. P. Aneesh, Mohamed A. Abdelgawad, Mohammed M. Ghoneim, Orazio Nicolotti, Subin Mary Zachariah, Bijo Mathew
Summary: Anti-inflammatory medications are commonly used over-the-counter drugs due to their relation to inflammation and pain caused by various diseases. Extensive research is required to develop effective and safe anti-inflammatory therapies. A 3D-QSAR model was built using a pharmacophore hypothesis, and virtual screening was used to identify potential compounds for COX-2 inhibition.
JOURNAL OF MOLECULAR STRUCTURE
(2024)
Article
Biochemistry & Molecular Biology
Dhananjay D. Jade, Rajan Pandey, Rakesh Kumar, Dinesh Gupta
Summary: In this study, small molecule inhibitors targeting TNF-α were identified using various computational methods. The results showed that these inhibitors had better binding energies compared to known inhibitors and exhibited stable binding with TNF-α protein. Sixteen compounds passed ADMET analysis, indicating their potential for designing future effective TNF-α inhibitors.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Vibhu Jha, Salvatore Galati, Valerio Volpi, Lidia Ciccone, Filippo Minutolo, Flavio Rizzolio, Carlotta Granchi, Giulio Poli, Tiziano Tuccinardi
Summary: ACLY is an important enzyme involved in fatty acid synthesis and could be a promising target for anticancer drug design. Through virtual screening, compound VS1 with potential inhibitory activity was identified, showing a 2.5 times higher potency than the reference inhibitor 2-hydroxycitrate.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Chemistry, Physical
Mohsen Yazdani, Ameneh Jafari, Soodeh Mahdian, Mohsen Namazi, Sajjad Gharaghani
Summary: The lack of effective treatment for the current coronavirus family pan-demic, particularly COVID-19, has created the need to identify potential inhibitor candidates to disrupt the binding of the virus to host cells. This study proposes a computational screening method to identify such inhibitors, with the compound PubChem-84280085 identified as a potential candidate.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Article
Biochemistry & Molecular Biology
Jannat Ul Firdaus, Nadeem Siddiqui, Ozair Alam, Ajay Manaithiya, Kailash Chandra
Summary: Pharmacophore modelling, 3D QSAR modelling, virtual screening, and molecular dynamics study were combined to design and develop an alpha-glucosidase inhibitor. The study found that Gaussian steric characteristic plays a crucial role in the inhibitory potential of alpha glucosidase. The developed 3D QSAR model showed a good predictive ability for the training and testing sets.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Medicine, Research & Experimental
Mahmoud Ganji, Shohreh Bakhshi, Alireza Shoari, Reza Ahangari Cohan
Summary: This study utilized pharmacophore and QSAR modeling to identify five potential FGFR3 inhibitors for bladder cancer treatment, which showed promising therapeutic properties and low toxicity levels.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Arif Jamal Siddiqui, Sadaf Jahan, Mitesh Patel, Abdelmushin Abdelgadir, Wael Alturaiki, Fevzi Bardakci, Manojkumar Sachidanandan, Riadh Badraoui, Mejdi Snoussi, Mohd Adnan
Summary: This study identifies six new inhibitors against the EGFR protein using computational approaches. These molecules show high docking scores and FEC values, as well as stable RMSD plots and strong hydrogen interactions. These findings have potential implications for developing new drugs to treat breast cancer.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
Lianxiang Luo, Ai Zhong, Qu Wang, Tongyu Zheng
Summary: In this study, marine natural compound 51320 was identified as a small molecule inhibitor of PD-L1 through various screening methods.
Article
Biochemistry & Molecular Biology
Giulio Poli, Miriana Di Stefano, Joan Arias Estevez, Filippo Minutolo, Carlotta Granchi, Antonio Giordano, Salvatore Parisi, Matteo Mauceri, Vincenzo Canzonieri, Marco Macchia, Isabella Caligiuri, Tiziano Tuccinardi, Flavio Rizzolio
Summary: This study reports the virtual screening and identification of potential PIN1 inhibitors with anti-tumoral activity. The results confirm the reliability of the in silico protocol and provide new ligands as starting points for the development of PIN1 inhibitors.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Arooma Maryam, Abdul Rauf Siddiqi, Sundeep Chaitanya Vedithi, Abdulilah Ece, Rana Rehan Khalid
Summary: Through e-pharmacophore based screening and molecular dynamics simulation, we have discovered compounds that selectively inhibit PDE5A compared to PDE6A. These compounds stably bind to PDE5A and show weaker binding to PDE6A. After optimization and therapeutic interventions, this compound may become a promising PDE5A selective inhibitor.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Alankar Roy, Shreya Luharuka, Ishani Paul, Sujay Ray
Summary: Through various bioinformatics techniques, a potential inhibitor of USP21 called ZINC02422616 was discovered. This compound exhibits the same pharmacophoric features as other USP21 inhibitors and demonstrates a high binding affinity for the USP21 domain. It has favorable pharmacokinetic, pharmacodynamic, and ADMET properties, as well as strong hydrophobic interaction and hydrogen bonding with the domain. Simulation studies showed that the complex remains stable over time, with the ligand displaying a highly favorable free energy landscape and multiple energy minima, indicating a high affinity for the target domain. This potential drug candidate can be utilized as an effective treatment for various cancers caused by USP21.
JOURNAL OF MOLECULAR RECOGNITION
(2023)
Article
Biology
Kamrul Hasan Chowdhury, Md. Riad Chowdhury, Shafi Mahmud, Abu Montakim Tareq, Nujhat Binte Hanif, Naureen Banu, A. S. M. Ali Reza, Talha Bin Emran, Jesus Simal-Gandara
Summary: This study utilized computational methods to search for active drugs for the treatment of novel coronavirus disease and identified several established drugs that could be further analyzed. The effectiveness of the retrieved drugs was proven, recommending further scrutiny for the development of drugs against novel coronavirus.
Article
Biochemistry & Molecular Biology
Xianglin Chu, Siyu He, Yang Liu, Yijun Liu, Feng Feng, Qinglong Guo, Li Zhao, Haopeng Sun
Summary: This article provides an overview of the physiological and pathological functions of human aldo-keto reductase family 1C1 (AKR1C1) and its relationship with diseases. It also summarizes the development of AKR1C1 inhibitors and the interaction between inhibitors and AKR1C1. Furthermore, it discusses the design ideals of selective AKR1C1 inhibitors and the prospects of AKR1C1 in disease treatment.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Chemistry, Multidisciplinary
Lei Wang, Chenxi Du, Hui Liu, Weimin Qiu, Xin Lu, Yanyu Hu, Yueqing Li, Tianyu Sun, Yao Chen, Haopeng Sun
Summary: In this study, small-molecule fluorescence probes for BChE were designed and shown to have potential in detecting the affinity of non-fluorescent compounds to BChE. This provides a solid foundation for the development of small-molecule BChE inhibitors and better understanding the molecular biological mechanism of BChE.
CHINESE JOURNAL OF CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Yuanyuan Wang, Baichen Xiong, Shuaishuai Xing, Ying Chen, Qinghong Liao, Jun Mo, Yao Chen, Qi Li, Haopeng Sun
Summary: Tyrosinase is a bifunctional enzyme involved in melanogenesis. It is targeted for various applications such as skin whitening, anticancer treatment, antibacterial properties, and fruit and vegetable preservation. Medicinal chemists have developed diverse tyrosinase inhibitors with novel scaffolds and synergistic effects to regulate multiple targets. This review covers natural and synthetic tyrosinase inhibitors with potential applications in various fields.
CURRENT MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Xuemei Wei, Guoqi Yu, Hualiang Shen, Yanjuan Luo, Tianbo Shang, Runpu Shen, Meiyang Xi, Haopeng Sun
Summary: Phosphodiesterase 4 (PDE4), highly expressed in mammalian brain, selectively hydrolyzes cAMP, a key regulator of brain functions such as learning and memory. Inhibiting PDE4 can improve cognitive deficits, but its clinical development is hindered by adverse effects. Research on PDE4 subtypes and the development of subtype-specific inhibitors show promise for improved therapeutic benefits and safety.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Yang Liu, Yuting Chen, Jiheng Jiang, Xianglin Chu, Qinglong Guo, Li Zhao, Feng Feng, Wenyuan Liu, Xiaolong Zhang, Siyu He, Peng Yang, Pengfei Fang, Haopeng Sun
Summary: AKR1C3 is overexpressed in hormone-related cancers and is correlated with tumor development and aggressiveness. A new class of AKR1C3 inhibitors with potent inhibitory activity and selectivity for closely related isoforms has been developed. Co-administration of these inhibitors with doxorubicin can significantly reverse drug resistance in breast cancer cells. These AKR1C3 inhibitors may serve as effective adjuvants to overcome drug resistance in breast cancer treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Yuanyuan Wang, Baichen Xiong, Hongzhi Lin, Qi Li, Hongyu Yang, Yuting Qiao, Qihang Li, Ziwei Xu, Weiping Lyu, Wei Qu, Wenyuan Liu, Yao Chen, Feng Feng, Haopeng Sun
Summary: Designing and synthesizing multifunctional anti-AD hybrids, we found that the optimal hybrid 15a exhibited excellent AChE inhibitory activity and significant Nrf2 inductivity. It showed neuroprotective, antioxidant, and anti-inflammatory effects, improved cognition, and reduced proinflammatory factors levels. These findings highlight the potential of 15a as a promising compound for further research in AD treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Editorial Material
Chemistry, Multidisciplinary
Xianqing Deng, Haopeng Sun, Bahaa G. M. Youssif
FRONTIERS IN CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Hualiang Shen, Xinde Xu, Yalong Bai, Xiaoping Wang, Yibin Wu, Jia Zhong, Qiyi Wu, Yanjuan Luo, Tianbo Shang, Runpu Shen, Meiyang Xi, Haopeng Sun
Summary: The Kynurenine pathway (KP) is the primary pathway of L-tryptophan metabolism in mammals, and it produces neuroactive metabolites such as kynurenic acid (KA) and quinolinic acid (QA). Imbalance in KP has been associated with aging and neurodegenerative diseases (NDs), leading to the interest in targeting KP enzymes and metabolite-associated receptors, particularly kynurenine monooxygenase (KMO). Although several agents have shown significant improvement in animal models, only one aryl hydrocarbon receptor (AHR) agonist 30 (laquinimod) has entered clinical trials for treating Huntington's disease (HD). This review provides an overview of neuroactive KP metabolites, discusses KP dysregulation in aging and NDs, and summarizes the development of KP regulators in preclinical and clinical studies, offering insights into the potential of targeting KP for NDs treatment in the future.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Xu Tang, Shuaishuai Xing, Mingkang Ma, Ziwei Xu, Qianwen Guan, Yuting Chen, Feng Feng, Wenyuan Liu, Tingkai Chen, Yao Chen, Haopeng Sun
Summary: Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2), which is the most common genetic risk factor for PD. This publication provides a comprehensive overview of the structure, function, and mutations of LRRK2, as well as recent advances and challenges in developing LRRK2 inhibitors. The binding mechanisms, structure-activity relationships, and pharmacokinetic features of inhibitors are emphasized to guide the rational design of LRRK2 inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Lu Lu, Jingyi Chen, Wenxiang Tao, Zhimei Wang, Dan Liu, Jiahui Zhou, Xiaoxing Wu, Haopeng Sun, Wei Li, Genzoh Tanabe, Osamu Muraoka, Bo Zhao, Liang Wu, Weijia Xie
Summary: We attempted double-spot structural modification on a side-chain moiety of sulfonium-type alpha-glucosidase inhibitors isolated from Salacia genus. We designed and synthesized a series of sulfonium salts with benzylidene acetal linkage at the C3 ' and C5 ' positions. In vitro enzyme inhibition evaluation showed that compounds with a strong electron-withdrawing group attached at the ortho position on the phenyl ring have stronger inhibitory activities. Notably, the most potent inhibitor 21b showed excellent hypoglycemic effects in mice, comparable to acarbose. Molecular docking of 21b revealed the importance of the newly introduced benzylidene acetal moiety in anchoring the molecule in the enzyme's concave pocket. The identification of 21b as a lead compound may enable structure modification and diversification of sulfonium-type alpha-glucosidase inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Haojie Dong, Xiuquan Ye, Yasheng Zhu, Hao Shen, Hongtao Shen, Weijiao Chen, Minghui Ji, Mingming Zheng, Keren Wang, Zeyu Cai, Haopeng Sun, Yibei Xiao, Peng Yang
Summary: In this study, a series of Osimertinib derivatives were designed as fourth-generation inhibitors targeting Osimertinib-resistant NSCLC. The top candidate D51 showed potent inhibition against EGFR mutants, selectivity against wild-type forms, and favorable in vivo druggability.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Weimin Qiu, Hui Liu, Yijun Liu, Xin Lu, Lei Wang, Yanyu Hu, Feng Feng, Qi Li, Haopeng Sun
Summary: Alzheimer's disease (AD) is a difficult to treat progressive neurodegenerative disease characterized by the accumulation of amyloid beta (A beta) plaques in the brain. A beta interacts with various receptors on the plasma membrane and mediates signaling pathways that contribute to the development of AD. Despite ongoing research, there are currently no effective medications for AD. This review discusses the importance of A beta in the pathogenesis of AD, recent progress in targeting A beta-related receptors and compounds, and the challenges and opportunities in developing effective therapies for AD.
MEDICINAL RESEARCH REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Chang Liu, Manxing Zou, Jianguo Zuo, Huanfang Xie, Weiping Lyu, Jian Xu, Feng Feng, Haopeng Sun, Wenyuan Liu, Xueyang Jiang
Summary: The FDA has approved donepezil, a selective AChE inhibitor, as a first-line drug for mild to moderate AD, but patients taking donepezil often experience peripheral side effects. This study introduces a series of novel thiazole salt AChE inhibitors with nanomolar inhibitory effect on human AChE. Thiamine disulfide prodrugs based on these inhibitors are developed and shown to be converted into thiazole salt AChE inhibitors in the brain, with high brain exposure and stronger inhibitory effects compared to intestinal AChE in vivo. This study provides a possible basis for centrally targeted thiazole salt inhibitors in the treatment of neurodegenerative diseases.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Siyu He, Xianglin Chu, Yujia Wu, Jiheng Jiang, Pengfei Fang, Yuting Chen, Yang Liu, Zhixia Qiu, Yibei Xiao, Zhiyu Li, Di Pan, Qian Zhang, Huanfang Xie, Shuaishuai Xing, Feng Feng, Wenyuan Liu, Qinglong Guo, Li Zhao, Peng Yang, Haopeng Sun
Summary: Aldo-keto reductase 1C3 (AKR1C3) has been found to be associated with tumor development and chemotherapy resistance. Inhibition of AKR1C3 activity can restore the chemosensitivity in ANT-resistant cancers. Biaryl-containing AKR1C3 inhibitors, particularly S07-1066, selectively block AKR1C3-mediated reduction and significantly enhance the cytotoxicity of doxorubicin (DOX) in MCF-7 cells overexpressing AKR1C3. The synergistic effect of S07-1066 and DOX has been demonstrated in vitro and in vivo, suggesting that AKR1C3 inhibitors may serve as effective adjuvants to overcome AKR1C3-mediated chemotherapy resistance.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Xu Tang, Shuaishuai Xing, Mingkang Ma, Ziwei Xu, Qianwen Guan, Yuting Chen, Feng Feng, Wenyuan Liu, Tingkai Chen, Yao Chen, Haopeng Sun
Summary: Parkinson's disease is a neurodegenerative disorder that affects millions of people worldwide. Mutations in the LRRK2 gene are the most common genetic risk factor for PD. Elevated LRRK2 kinase activity is found in both idiopathic and familial PD cases. LRRK2 mutations are involved in various PD pathogeneses, including dysregulation of mitochondrial homeostasis and ciliogenesis.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)