Article
Biochemistry & Molecular Biology
Ahmed M. Abdelhamed, Rasha A. Hassan, Hanan H. Kadry, Amira A. Helwa
Summary: A novel series of 12 pyrazolo[3,4-d]pyrimidine derivatives were evaluated for their antiproliferative activity against human tumor cell lines, showing that compound 12b exhibited the highest anticancer activity against breast cancer cell lines and had potent VEGFR-2 inhibitory activity and angiogenesis inhibition potential.
RSC MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Jian-Bo Tong, Yi Feng, Ding Luo, Tian-Hao Wang
Summary: This study investigated the contribution of VEGFR-2 kinase inhibitors to their structures and proposed modification strategies. Reliable HQSAR and topomer CoMFA models were established, and molecular docking was used to study drug interactions and potential biological active conformations. The study provides insight into the design of potential anti-VEGFR-2 inhibitors.
Article
Biochemistry & Molecular Biology
Ibrahim H. Eissa, Radwan El-Haggar, Mohammed A. Dahab, Marwa F. Ahmed, Hazem A. Mahdy, Reem Alsantali, Alaa Elwan, Nicolas Masurier, Samar S. Fatahala
Summary: A novel series of compounds were designed and prepared, which showed potential antitumor activity and inhibitory effect on vascular endothelial growth factor receptor-2 (VEGFR-2), making them promising candidates for future anticancer therapy development.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Hany M. Abd El-Lateef, Mohammed A. I. Elbastawesy, Tamer Mohamed Abdelghani Ibrahim, Mai M. Khalaf, Mohamed Gouda, Mariam G. F. Wahba, Islam Zaki, Martha M. Morcoss
Summary: A new series of Schiff-benzimidazole hybrids 3a-o was synthesized and their structures were confirmed. The compounds were evaluated for their cytotoxic activity against cancer cell lines, showing promising results against lung cancer A549 and NCI-H460 cell lines. Compounds 3e and 3g exhibited the most potent activity and also showed significant inhibitory activity on VEGFR-2. Molecular docking studies confirmed the binding interactions with a similar mode and pose to Sorafenib.
Article
Biochemistry & Molecular Biology
Magda M. F. Ismail, Taghreed Z. Shawer, Rabab S. Ibrahim, Rasha M. Allam, Yousry A. Ammar
Summary: This study aims to explore the VEGFR-2 inhibitory activity of a novel library of quinoxalin-2-one derivatives and found that compound 7f displayed remarkable cytotoxicity against HCT-116 and MCF-7 cell lines. It also showed potential anti-migratory effect and induced apoptosis and cell cycle arrest. Molecular docking confirmed the affinity of these compounds for VEGFR-2 active site.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Alaa Elwan, Abdallah E. Abdallah, Hazem A. Mahdy, Mohammed A. Dahab, Mohammed S. Taghour, Eslam B. Elkaeed, Ahmed B. M. Mehany, Ahmed Nabeeh, Mohammed Adel, Aisha A. Alsfouk, Hazem Elkady, Ibrahim H. Eissa
Summary: This study focused on modifying previous work to develop VEGFR-2 inhibitors by synthesizing thirteen new compounds based on benzoxazole structure. The results showed that compound 8d exhibited stronger anticancer activity and VEGFR-2 inhibition compared to standard sorafenib.
Article
Oncology
Catarina Nascimento, Andreia Gameiro, Joao Ferreira, Jorge Correia, Fernando Ferreira
Summary: Feline mammary carcinoma is the third most common neoplasia in cats, with highly malignant behavior. The study suggests that VEGF-A and its serum receptors assessment may have potential in the diagnosis and treatment of feline mammary carcinoma.
Article
Biochemistry & Molecular Biology
Abdelfattah Hassan, Mohamed Badr, Heba A. Hassan, Dalia Abdelhamid, Gamal El-Din A. Abuo-Rahma
Summary: A new series of synthesized compounds showed high anticancer activity, with one dihalogenated derivative exhibiting the best cytotoxicity. Some compounds exhibited VEGFR-2 inhibitory activity similar to sorafenib, indicating potential antiproliferative effects.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Merve Zengin, Oya Unsal Tan, Reem Arafa, Ayla Balkan
Summary: This study designed and synthesized a series of novel compounds as potential antitumor agents and VEGFR-2 inhibitors. Eight compounds showed high growth inhibition against MCF-7 cells and possessed sub-micromolar range of VEGFR-2 inhibitory activity. Docking studies and in silico physicochemical predictions suggested promising drug-likeness profiles for these compounds.
BIOORGANIC CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Mahfam Moradi, Alireza Mousavi, Zahra Emamgholipour, Johanna Giovannini, Setareh Moghimi, Fariba Peytam, Amin Honarmand, Stephane Bach, Alireza Foroumadi
Summary: Angiogenesis is crucial for endothelial cell migration, growth, and differentiation, but dysregulated angiogenesis in tumor microenvironments contributes to tumor growth. VEGFR-2 inhibitors, especially quinazoline derivatives, have been approved for cancer treatment, but there are limitations in clinical efficacy and drug resistance. There is a need for the design and synthesis of more selective and effective inhibitors to overcome these challenges.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Heba K. A. El-Mawgoud, Ahmed M. Fouda, Mohammed A. A. El-Nassag, Ahmed A. Elhenawy, Mohammed Y. Alshahrani, Ahmed M. El-Agrody
Summary: A series of novel oxygen-containing heterocyclic linked 1H-benzo[f]chromene moieties were designed and synthesized, showing anti-proliferative activity against cancer cell lines, particularly MCF-7, HCT-116, and HepG-2. The compounds exhibited potential mechanisms involving cell cycle arrest and inhibition of topoisomerase enzymes.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Review
Cardiac & Cardiovascular Systems
Bronte Miller, Mary Kathryn Sewell-Loftin
Summary: Endothelial cells in the vascular system respond to mechanical forces, playing a critical role in maintaining blood vessel structure and function. Understanding the mechanisms of biomechanical regulation in vascular growth can lead to new therapeutic strategies for different diseases.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Adel S. Girgis, Siva S. Panda, Aladdin M. Srour, Anwar Abdelnaser, Soad Nasr, Yassmin Moatasim, Omnia Kutkat, Ahmed El Taweel, Ahmed Kandeil, Ahmed Mostafa, Mohamed A. Ali, Nehmedo G. Fawzy, Mohamed S. Bekheit, ElSayed M. Shalaby, Lara Gigli, Walid Fayad, Ahmed A. F. Soliman
Summary: Sets of 3-alkenyl-2-oxindoles were synthesized through acid dehydration of the corresponding 3-hydroxy-2-oxoindolines. Compounds 6c and 10b showed effective inhibition against pancreatic cancer cells and potential antiviral properties against SARS-CoV-2, with compound 10b also exhibiting antiproliferative properties against breast cancer cells. The compounds also demonstrated anti-angiogenic properties and multitargeted inhibitory activities against VEGFR-2 and c-kit, supporting their potential as therapeutic agents.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Neha Sharma, Mala Sharma, Qazi Inamur Rahman, Salman Akhtar, Mohd Muddassir
Summary: The study focused on exploring novel natural compounds targeting VEGFR-2 through computational modeling and database screening. Among the screened compounds, Compound B demonstrated the highest binding energy and stable binding to the active site of VEGFR-2, suggesting its potential as a potent antiangiogenic agent.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Biochemistry & Molecular Biology
Mohammed S. Taghour, Hazem A. Mahdy, Maher H. Gomaa, Ahmed Aglan, Mahmoud Gomaa Eldeib, Alaa Elwan, Mohammed A. Dahab, Eslam B. Elkaeed, Aisha A. Alsfouk, Mohamed M. Khalifa, Ibrahim H. Eissa, Hazem Elkady
Summary: In this study, a series of novel benzoxazole derivatives were designed, synthesized, and evaluated for their potential as VEGFR-2 inhibitors. Compound 12l showed high growth inhibitory activity against HepG2 and MCF-7 cell lines and demonstrated promising VEGFR-2 inhibitory activity. Further investigation revealed that 12l could arrest cell growth at the Pre-G1 and G1 phases, induce apoptosis, and regulate key proteins involved in apoptosis. Docking studies suggested that 12l interacted with key amino acids similar to sorafenib.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)