Article
Biochemistry & Molecular Biology
Maria Mushtaq Ali, Sajda Ashraf, Mohammad Nure-E-Alam, Urooj Qureshi, Khalid Mohammed Khan, Zaheer Ul-Haq
Summary: In this study, BRD9, BRD7, and BRD4 were compared, and several crucial residues conferring BRD9 isoform selectivity were identified. Potential BRD9 inhibitors were discovered through predicted pharmacophore mapping and docking-based virtual screening, and four compounds were selected for further molecular dynamics studies. These findings lay the foundation for the discovery of new compounds and understanding functional differences between isoforms and orthologues.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Nutrition & Dietetics
Sabeeta Kapoor, Elisabetta Damiani, Shan Wang, Ravirajan Dharmanand, Chakrapani Tripathi, Jorge Enrique Tovar Perez, Wan Mohaiza Dashwood, Praveen Rajendran, Roderick Hugh Dashwood
Summary: Epigenetic mechanisms, specifically the deregulation of bromodomain (BRD) functions, play a significant role in colorectal cancer (CRC) and other malignancies. This study shows that overexpression of BRD9 is associated with poor prognostic outcomes in CRC patients. Natural polyphenols such as Epigallocatechin-3-gallate (EGCG), Equol, Quercetin, and Aspalathin were identified as potential BRD9 antagonists, as they reduced colon cancer cell viability, inhibited colony formation, and increased DNA damage and apoptosis.
Article
Chemistry, Multidisciplinary
Sk Abdul Amin, Prakruti Trivedi, Nilanjan Adhikari, Ganesh Routholla, Dhanya Vijayasarathi, Sanjib Das, Balaram Ghosh, Tarun Jha
Summary: The study focused on designing pentanoic acid based hydroxamates as selective HDAC8 inhibitors, with compounds 7i and 7f identified as selective inhibitors that showed better antiproliferative activities against certain cancer cell lines and induced significant cell growth arrest in the G2/M phase. These findings suggest that these compounds could serve as lead molecules for further investigation into their anticancer potentials.
NEW JOURNAL OF CHEMISTRY
(2021)
Article
Engineering, Environmental
Tingting Ku, Xin Tan, Yutong Liu, Rui Wang, Lifan Fan, Zhihua Ren, Xia Ning, Guangke Li, Nan Sang
Summary: Considering the unavoidable exposure to triazole fungicides, it is crucial to investigate their developmental toxicity for health risk assessment. This study aimed to evaluate the neurodevelopmental effects of six triazole fungicides on mouse embryonic stem cells (mESCs) by analyzing their impact on neural differentiation and histone modification. The findings revealed that the fungicides induced alterations in neurogenesis, intracellular calcium ion levels, and neurotransmitter function, with the binding affinities between the fungicides and Kdm6b-ligand binding domain playing a key role. These results highlight the potential adverse impacts of triazole fungicides on embryonic neurogenesis through histone modification and provide evidence for their safety control.
JOURNAL OF HAZARDOUS MATERIALS
(2023)
Article
Oncology
Margarita E. Neganova, Sergey G. Klochkov, Yulia R. Aleksandrova, Gjumrakch Aliev
Summary: Epigenetic changes associated with histone modifications are important in the emergence and maintenance of various cancer types. Inhibitors of enzymes involved in these modifications are promising for anticancer drug development. This review explores the main features of common histone modifications and their role in malignant neoplasms, discussing strategies for inhibitor development and analyzing the use of multitarget drugs as the most promising strategy.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Simona De Vita, Maria Giovanna Chini, Giuseppe Bifulco, Gianluigi Lauro
Summary: The study used in silico molecular dynamics simulations to evaluate the binding of molecules to the BRD9 protein, guiding the identification of potential novel ligands. Parameters were calculated based on simulations of varying lengths, and the results were compared with molecular docking and experimental data to validate the method's reliability.
Article
Chemistry, Physical
Negar Omidkhah, Farzin Hadizadeh, Khalil Abnous, Razieh Ghodsi
Summary: A series of quinoline-based benzamide derivatives were designed and synthesized as HDAC inhibitors and anticancer agents. The synthesized compounds showed cytotoxic activity against several human cancer cell lines, with the highest cytotoxicity observed in colorectal cancer and lung cancer cells. Compounds with a methyl group at position 2 of the quinoline ring exhibited better cytotoxicity compared to those with an aryl group. The most potent cytotoxic compounds also displayed strong enzyme inhibitory activity.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Chemistry, Multidisciplinary
Syed Nazreen, Serag Eldin I. Elbehairi, Azizah M. Malebari, Nuha Alghamdi, Reem F. Alshehri, Ali A. Shati, Nada M. Ali, Mohammad Y. Alfaifi, Ahmed A. Elhenawy, Mohammad Mahboob Alam
Summary: Semisynthetic modification of eugenol has produced new anticancer agents, with compound 17 showing the highest cytotoxicity and being a thymidylate synthase inhibitor. It induced apoptosis, arrested the cell cycle, and displayed a similar interaction to 5-fluorouracil. In silico pharmacokinetics and DFT computational studies supported its potential as an orally available drug.
Article
Biochemistry & Molecular Biology
Linan Zhao, Le Fu, Guangping Li, Yongxin Yu, Juan Wang, Haoran Liang, Mao Shu, Zhihua Lin, Yuanqiang Wang
Summary: In this study, 3D-QSAR models were established to investigate the relationship between molecular structure and inhibitory activity for multivariate-substituted 4-oxyquinazoline HDAC6 inhibitors. The models showed good predictive ability and passed internal verification, external verification, and AD testing. Molecular docking and dynamics simulation were used to explore the interaction between compounds and HDAC6. The study provided theoretical references for designing compounds with higher activity and offered a new idea for the development of novel HDAC6 inhibitors.
MOLECULAR DIVERSITY
(2023)
Article
Biochemistry & Molecular Biology
Mora Massaro, Alejandro J. Cagnoni, Francisco J. Medrano, Juan M. Perez-Saez, Shuay Abdullayev, Karima Belkhadem, Karina Marino, Antonio Romero, Rene Roy, Gabriel A. Rabinovich
Summary: Galectin-1 (Gal-1), a member of the Galectin family, is overexpressed in several cancers and plays critical roles in tumor-immune escape, angiogenesis, and metastasis. This study evaluated different modifications of lactoside compounds as Gal-1 ligands and analyzed their binding affinities through competitive solid-phase assays and isothermal titration calorimetry. Molecular docking simulations and structure-based methods were used to predict the atomistic determinants for the preferential affinity. The study provides insights for the rational design of optimized Gal-1 inhibitors for cancer treatment.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Review
Plant Sciences
Rocio Nunez-Vazquez, Benedicte Desvoyes, Crisanto Gutierrez
Summary: Plants have developed various mechanisms to adapt to abiotic stresses, which involve transcriptional regulation and chromatin modifications. Understanding and manipulating these regulatory networks are crucial for enhancing crop resilience and performance against stress.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Laura Morales-Luna, Beatriz Hernandez-Ochoa, Victor Martinez-Rosas, Gabriel Navarrete-Vazquez, Daniel Ortega-Cuellar, Yadira Rufino-Gonzalez, Abigail Gonzalez-Valdez, Roberto Arreguin-Espinosa, Adrian Marcelo Franco-Vasquez, Veronica Perez de la Cruz, Sergio Enriquez-Flores, Carlos Martinez-Conde, Luis Miguel Canseco-Avila, Fernando Gomez-Chavez, Saul Gomez-Manzo
Summary: This study investigates new drugs against giardiasis by targeting enzyme inhibition. The results show that these drugs effectively inhibit the enzyme activity of the parasite and exhibit good anti-giardial activity in Giardia lamblia while having low toxicity to human cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Min Zou, Jiawen Li, Bo Jin, Mingsheng Wang, Huiping Chen, Zhuangli Zhang, Changzheng Zhang, Zhihong Zhao, Liyun Zheng
Summary: Dual targeting of EGFR/HER2 receptors is an attractive strategy for cancer therapy. Compound 6d, a 4-anilinoquinoline-3-carbonitrile derivative, showed significant antiproliferative activity against SK-BR-3 and A431 cell lines, with potency comparable to Lapatinib and higher than Neratinib. Molecular docking studies indicated the binding modes of compound 6d in EGFR and HER2 binding sites, suggesting it as a potential candidate for further investigation as a potent anticancer agent.
BIOORGANIC CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Maria Mushtaq Ali, Sehrish Naz, Sajda Ashraf, Stefan Knapp, Zaheer Ul-Haq
Summary: BRD9 inhibitors have potential therapeutic value in cancer treatment by selectively targeting BRD9 and BRD7 proteins, regulating chromatin structure and gene expression, and inhibiting tumor growth and progression.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Medicinal
Jingyu Zhang, Haiting Duan, Renzhao Gui, Mingfei Wu, Liteng Shen, Yuheng Jin, Ao Pang, Xiaoli Yu, Shenxin Zeng, Bo Zhang, Nengming Lin, Wenhai Huang, Yuwei Wang, Xiaojun Yao, Jia Li, Xiaowu Dong, Yubo Zhou, Jinxin Che
Summary: This study describes an oral activity BRD9 PROTAC C6 that recruits a highly efficient E3 ligase to degrade BRD9, showing potential therapeutic effects against AML cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)