Molecular Dynamics and Machine Learning reveal distinguishing mechanisms of Competitive Ligands to perturb α,β-Tubulin
Comput Biol Chem. 2023 Dec 14;108:108004. doi: 10.1016/j.compbiolchem.2023.108004. Online ahead of print.ABSTRACTThe mechanisms of action of ligands competing for the Colchicine Binding Site (CBS) of the α,β-Tubulin are non-standard compared to the commonly witnessed ligand-induced inhibition of proteins. This is because their potencies are not solely judged by the binding affinity itself, but also by their capacity to bias the conformational states of the dimer. Regarding the latter requirement, it is observed that ligands competing for the same pocket that binds colchicine exhibit divergence in potential clinical outco...
Source: Computational Biology and Chemistry - December 29, 2023 Category: Bioinformatics Authors: Debadrita Basu Shubhra Ghosh Dastidar Source Type: research
Discovery of novel coumarin-based derivatives as inhibitors of tubulin polymerization targeting the colchicine binding site with potent anti-gastric cancer activities
Eur J Med Chem. 2023 Dec 22;265:116079. doi: 10.1016/j.ejmech.2023.116079. Online ahead of print.ABSTRACTIn this work, a series of novel coumarin-based derivatives were designed and synthesized as tubulin polymerization inhibitors targeting the colchicine binding site, and their antiproliferative activities against MGC-803, HCT-116 and KYSE30 cells were evaluated. Among them, the compound I-3 (MY-1442) bearing a 6-methoxy-1,2,3,4-tetrahydroquinoline group exhibited most potent inhibitory activities on MGC-803 (IC50 = 0.034 μM), HCT-116 (IC50 = 0.081 μM) and KYSE30 cells (IC50 = 0.19 μM). Further mechanism studies demons...
Source: European Journal of Medicinal Chemistry - December 27, 2023 Category: Chemistry Authors: Xin-Yi Tian Wei-Xin Zhang Xiao-Yu Chen Mei-Qi Jia Sai-Yang Zhang Yi-Fan Chen Shuo Yuan Jian Song Jia Li Source Type: research
Discovery of novel coumarin-based derivatives as inhibitors of tubulin polymerization targeting the colchicine binding site with potent anti-gastric cancer activities
Eur J Med Chem. 2023 Dec 22;265:116079. doi: 10.1016/j.ejmech.2023.116079. Online ahead of print.ABSTRACTIn this work, a series of novel coumarin-based derivatives were designed and synthesized as tubulin polymerization inhibitors targeting the colchicine binding site, and their antiproliferative activities against MGC-803, HCT-116 and KYSE30 cells were evaluated. Among them, the compound I-3 (MY-1442) bearing a 6-methoxy-1,2,3,4-tetrahydroquinoline group exhibited most potent inhibitory activities on MGC-803 (IC50 = 0.034 μM), HCT-116 (IC50 = 0.081 μM) and KYSE30 cells (IC50 = 0.19 μM). Further mechanism studies demons...
Source: European Journal of Medicinal Chemistry - December 27, 2023 Category: Chemistry Authors: Xin-Yi Tian Wei-Xin Zhang Xiao-Yu Chen Mei-Qi Jia Sai-Yang Zhang Yi-Fan Chen Shuo Yuan Jian Song Jia Li Source Type: research
Microtubule destabilising activity of selected 7-methoxy-2-phenylbenzo[b]furan derivative against primary and metastatic melanoma cells
Eur J Pharmacol. 2023 Dec 22:176308. doi: 10.1016/j.ejphar.2023.176308. Online ahead of print.ABSTRACTHerein, we report the results of anticancer screening of two 2-phenylbenzo[b]furan derivatives functionalised at the 3-position with 4-hydroxy-3,5-dimethoxybenzoyl (BF2) or 3,4,5-trimethoxybenzoyl (BF3) against 60 different cancer cell lines. The results confirmed the anticancer potential of the tested compounds against different cancer cell types, especially colon cancer, brain cancer and melanoma. BF3 was defined as the most potent (also as a tubulin polymerisation inhibitor). Its anticancer activity against melanoma cel...
Source: European Journal of Pharmacology - December 24, 2023 Category: Drugs & Pharmacology Authors: Magdalena Peru żyńska Rados ław Birger Katarzyna Piotrowska Halina Kwiecie ń Marek Dro ździk Mateusz Kurzawski Source Type: research
The clinical role of Anakinra in the armamentarium against familial mediterranean fever
Expert Rev Clin Immunol. 2023 Dec 22. doi: 10.1080/1744666X.2023.2299230. Online ahead of print.ABSTRACTINTRODUCTION: Familial Mediterranean Fever (FMF) is the most common autoinflammatory disease that has mainly been treated with colchicine since 1972. A significant portion of patients do not respond to colchicine and require further treatment, mainly IL-1β antagonists such as anakinra, canakinumab and rilonacept as IL-1β has a crucial role in pathogenesis of FMF. This review summarizes the current approach to treating FMF and discovers the pharmacological and clinical utility of IL-1 blocking agents based on accumulate...
Source: Expert Review of Clinical Immunology - December 22, 2023 Category: Allergy & Immunology Authors: Kerem Parlar Muhammed Bahaddin Ates Bugra Han Egeli Serdal Ugurlu Source Type: research
Colchicine ameliorates short-term abdominal aortic aneurysms by inhibiting the expression of NLRP3 inflammasome components in mice
CONCLUSIONS: Our study demonstrates the effectiveness of colchicine in suppressing NLRP3 inflammasome components, thereby delaying AAA progression in the Ang II and CaCl2-induced short-term model. These findings suggest the potential of colchicine as a pharmacological treatment option for AAA.PMID:38135264 | DOI:10.1016/j.ejphar.2023.176297 (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - December 22, 2023 Category: Drugs & Pharmacology Authors: Jiaxin Hu Jiamin Xu Jiling Zhao Yuwei Liu Rui Huang Dejiang Yao Jun Xie Yuhua Lei Source Type: research
Anthraquinones from the roots of Morinda scabrida Craib exhibit antiproliferative activity against A549 lung cancer cells and antitubulin polymerization
Fitoterapia. 2023 Dec 19:105781. doi: 10.1016/j.fitote.2023.105781. Online ahead of print.ABSTRACTSix anthraquinones were isolated from Morinda scabrida Craib, an unexplored species of Morinda found in the tropical forest of Thailand. All six anthraquinones showed cytotoxicity against A549 lung cancer cells, with the most active compound, nordamnacanthal (MS01), exhibiting the IC50 value of 16.3 ± 2.5 μM. The cytotoxic effect was dose-dependent and led to cell morphological changes characteristic of apoptosis. In addition, flow cytometric analysis showed dose-dependent apoptosis induction and the G2/M phase cell cycle ar...
Source: Fitoterapia - December 21, 2023 Category: Biochemistry Authors: Sorachai Sae-Lim Lukana Ngiwsara Kriengsak Lirdprapamongkol Thamrongjet Puttamuk Sutida Maneeanakekul Poomsith Thangsan Withsakorn Sangsuwan Jisnuson Svasti Pitak Chuawong Source Type: research
Anthraquinones from the roots of Morinda scabrida Craib exhibit antiproliferative activity against A549 lung cancer cells and antitubulin polymerization
Fitoterapia. 2023 Dec 19:105781. doi: 10.1016/j.fitote.2023.105781. Online ahead of print.ABSTRACTSix anthraquinones were isolated from Morinda scabrida Craib, an unexplored species of Morinda found in the tropical forest of Thailand. All six anthraquinones showed cytotoxicity against A549 lung cancer cells, with the most active compound, nordamnacanthal (MS01), exhibiting the IC50 value of 16.3 ± 2.5 μM. The cytotoxic effect was dose-dependent and led to cell morphological changes characteristic of apoptosis. In addition, flow cytometric analysis showed dose-dependent apoptosis induction and the G2/M phase cell cycle ar...
Source: Fitoterapia - December 21, 2023 Category: Biochemistry Authors: Sorachai Sae-Lim Lukana Ngiwsara Kriengsak Lirdprapamongkol Thamrongjet Puttamuk Sutida Maneeanakekul Poomsith Thangsan Withsakorn Sangsuwan Jisnuson Svasti Pitak Chuawong Source Type: research
Adult-onset chronic recurrent multifocal osteomyelitis: a case report
This report presents an adult-onset female patient who presented with left leg pain followed by swelling in the right knee. The patient was initially started on colchicine treatment, but, due to unresponsiveness in the follow-up the patient, the treatment was switched to a combination of methotrexate and prednisolone. A satisfactory clinical recovery was achieved with these drugs. CRMO could be considered in the differential diagnosis of patients presenting with bone pain and joint complaints. Considering that the disease progresses with clinical flare-ups and remission periods, it should be kept in mind that patients shou...
Source: Skeletal Radiology - December 20, 2023 Category: Radiology Source Type: research
Correction: Transition to rilonacept monotherapy from oral therapies in patients with recurrent pericarditis
This article has been corrected since it was first published. A sentence in the Results section incorrectly stated "patients receiving colchicine and glucocorticoids at baseline demonstrated comparable transition to rilonacept monotherapy". This has now been corrected to "patients receiving colchicine and NSAIDs at baseline demonstrated comparable transition to rilonacept monotherapy". (Source: Heart)
Source: Heart - December 20, 2023 Category: Cardiology Tags: Open access Corrections Source Type: research
Separable and Inseparable Silk Fibroin Microneedles for the Transdermal Delivery of Colchicine: Development, Characterization, and Comparisons
In conclusion, the separable silk fibroin-based microneedles provide a promising route for colchicine delivery.PMID:38114734 | DOI:10.1208/s12249-023-02716-3 (Source: AAPS PharmSciTech)
Source: AAPS PharmSciTech - December 19, 2023 Category: Drugs & Pharmacology Authors: Shiji Liao Guirong Qiu Yanping Hu Bohong Guo Yuqin Qiu Source Type: research
Do we consider enough the presence of triggering factors in the evaluation of patients with FMF? Triggering factors are highly prevalent in colchicine-resistant FMF patients
In this study, triggering factors were more frequent in colchicine-resistant patients as compared to colchicine-responsive patients. Treatment with IL-1 antagonists seems to increase the endurance of colchicine-resistant patients in str essful conditions. (Source: Internal and Emergency Medicine)
Source: Internal and Emergency Medicine - December 16, 2023 Category: Emergency Medicine Source Type: research
A novel microtubule inhibitor promotes tumor ferroptosis by attenuating SLC7A11/GPX4 signaling
Cell Death Discov. 2023 Dec 13;9(1):453. doi: 10.1038/s41420-023-01713-6.ABSTRACTMP-HJ-1b is a novel microtubule inhibitor that we designed and reported previously. Ferroptosis is a newly identified type of nonapoptotic cell death induced by ferrous catalysis and lipid peroxidation. Here, transcriptomics, proteomics, and molecular docking analyses were combined to explore the novel effects of MP-HJ-1b on tumors. Both omics analyses suggested that MP-HJ-1b affects ribosomes, and we confirmed that it inhibits the ribosomal component proteins RPL35 and MRPL28. Colchicine was used as an analog, and the results showed that MP-H...
Source: Cancer Control - December 12, 2023 Category: Cancer & Oncology Authors: Nannan Ning Ziqi Shang Zhiping Liu Zhizhou Xia Yang Li Ruibao Ren Hongmei Wang Yi Zhang Source Type: research
