Future medicinal chemistry最新文献_第3页

A call to develop tramadol enantiomer for overcoming the tramadol crisis by reducing addiction.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-01 Epub Date: 2025-02-11 DOI: 10.1080/17568919.2025.2463314

Ilaria D'Acquarica, Israel Agranat

引用次数: 0

Protein profiling uncovers IGF-1R inhibition potential of 3-(2-furoyl)-indole scaffolds in hepatocellular carcinoma.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-01 Epub Date: 2025-03-03 DOI: 10.1080/17568919.2025.2467616

Efficiency Myrsing, H M Chandra Mouli, Pallaprolu Nikhil, Deepali, Abhishek Sahu, Anupam Jana, P Ramalingam

{"title":"Protein profiling uncovers IGF-1R inhibition potential of 3-(2-furoyl)-indole scaffolds in hepatocellular carcinoma.","authors":"Efficiency Myrsing, H M Chandra Mouli, Pallaprolu Nikhil, Deepali, Abhishek Sahu, Anupam Jana, P Ramalingam","doi":"10.1080/17568919.2025.2467616","DOIUrl":"10.1080/17568919.2025.2467616","url":null,"abstract":"Aim: This study investigates the anti-proliferative potential and possible molecular mechanisms of 3-(2-furoyl)-indole derivatives against HepG2.Method: Identified hit compounds (4a, 4b, 4c) using MTT screening, were further investigated for their efficacy and mechanism of action through FACS studies, in-silico molecular docking, molecular dynamics (MD) simulations, and label-free quantitative proteome and ADMET prediction.Results: Lead compound 4a, showed IC50 of 27 µM against HepG2 cells and a binding score of -8.077 kcal/mol against IGF-1 R (PDB ID: 5XFS) and formed a stable complex 100 ns. Proteomic study revealed significant downregulation of the IGF-1 R downstream signaling molecules and showed minimal toxicity and favorable drug-like properties.Conclusion: These findings suggest that 4a is a promising IGF-1 R inhibitor and potential drug candidate against drug resistance hepatocellular carcinoma (HCC).","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"513-528"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

3,5-Disubstituted pyrazoline as a promising core for anticancer agents: mechanisms of action and therapeutic potentials.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-01 Epub Date: 2025-03-13 DOI: 10.1080/17568919.2025.2476393

Basma S Gabr, Abdelrahman R Shalabi, Mona F Said, Riham F George

引用次数: 0

Targeting cyclin-dependent kinase 2 (CDK2) interactions with cyclins and Speedy 1 (Spy1) for cancer and male contraception.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-01 Epub Date: 2025-03-04 DOI: 10.1080/17568919.2025.2463868

Jeanine Giarolla, Kelsey A Holdaway, Maryam Nazari, Laila Aiad, Bidisha Sarkar, Gunda I Georg

引用次数: 0

Applications of carbon-silicon bioisosterism in drug design and development.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-01 Epub Date: 2025-02-07 DOI: 10.1080/17568919.2025.2463883

Jean Fotie

引用次数: 0

Experimental and Computational Investigation of Cu(II) and Zn(II) complexes: DFT, Docking, and Anti-Lung Cancer Studies.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-01 Epub Date: 2025-03-21 DOI: 10.1080/17568919.2025.2478815

Ummi Liyana Mohamad Rodzi, Karimah Kassim, Muhamad Azwan Hamali, Amalina Mohd Tajuddin, Maslinda Musa, Nur Amira Zulkifli, Fazira Ilyana Abdul Razak, Suhaila Sapari

{"title":"Experimental and Computational Investigation of Cu(II) and Zn(II) complexes: DFT, Docking, and Anti-Lung Cancer Studies.","authors":"Ummi Liyana Mohamad Rodzi, Karimah Kassim, Muhamad Azwan Hamali, Amalina Mohd Tajuddin, Maslinda Musa, Nur Amira Zulkifli, Fazira Ilyana Abdul Razak, Suhaila Sapari","doi":"10.1080/17568919.2025.2478815","DOIUrl":"10.1080/17568919.2025.2478815","url":null,"abstract":"Aims: This study aimed to synthesize and characterize a Schiff base ligand, (Z)-2-(2-oxoindolin-3-ylidene)hydrazinecarbothioamide (1), and its copper(II) (2) and zinc(II) (3) complexes, as well as evaluate their binding interactions with the epidermal growth factor receptor (EGFR) and anticancer activity against the human lung cancer A549 cell line.Materials & methods: The Schiff base ligand was synthesized by refluxing isatin and thiosemicarbazide for 3 hours. Complexes 2 and 3 were formed and characterized using elemental analysis, molar conductivity, IR, NMR, and UV-Visible spectroscopy. The geometry of complex 3 was determined via X-ray diffraction. Theoretical calculations were conducted using DFT with the hybrid GEN B3LYP method. Molecular docking was performed to assess binding energies with EGFR, and anticancer activity was evaluated against the A549 cell line.Results: Characterization confirmed successful synthesis of the compounds. Zinc complexation led to notable spectral shifts, and X-ray diffraction revealed complex 3 adopted a distorted tetrahedral geometry. DFT analysis highlighted complex 2 with the lowest energy gap (0.331 eV). Docking results showed strong EGFR binding energies (-5.70, -5.54, and -7.30 kcal/mol). Complex 2 demonstrated the highest anticancer efficacy with a cell viability of 1.35% after 48 h.Conclusions: Complex 2 exhibits significant anticancer potential and warrants further investigation as a therapeutic agent.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"669-679"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Refinement of MEK inhibitors.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-01 Epub Date: 2025-02-05 DOI: 10.1080/17568919.2025.2463311

Ankit Kumar Singh, Adarsh Kumar, Harshwardhan Singh, Amita Verma, Pradeep Kumar

引用次数: 0

Recent advances in targeted degradation in the RAS pathway.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-01 Epub Date: 2025-03-10 DOI: 10.1080/17568919.2025.2476387

Zhiming Ge, Zisheng Fan, Wei He, Guizhen Zhou, Yidi Zhou, Mingyue Zheng, Sulin Zhang

{"title":"Recent advances in targeted degradation in the RAS pathway.","authors":"Zhiming Ge, Zisheng Fan, Wei He, Guizhen Zhou, Yidi Zhou, Mingyue Zheng, Sulin Zhang","doi":"10.1080/17568919.2025.2476387","DOIUrl":"10.1080/17568919.2025.2476387","url":null,"abstract":"RAS (rat sarcoma) is one of the most frequently mutated gene families in cancer, encoding proteins classified as small GTPases. Mutations in RAS proteins result in abnormal activation of the RAS signaling pathway, a key driver in the initiation and progression of various malignancies. Consequently, targeting RAS proteins and the RAS signaling pathway has become a critical strategy in anticancer therapy. While RAS was historically considered an \"undruggable\" target, recent breakthroughs have yielded inhibitors specifically targeting KRASG12C and KRASG12D mutations, which have shown clinical efficacy in patients. However, these inhibitors face limitations due to rapid acquired resistance and the toxic effects of combination therapies in clinical settings. Targeted protein degradation (TPD) strategies, such as PROTACs and molecular glues, provide a novel approach by selectively degrading RAS proteins, or their upstream and downstream regulatory factors, to block aberrant signaling pathways. These degraders offer a promising alternative to traditional inhibitors by potentially circumventing resistance and enhancing therapeutic precision. This review discusses recent advancements in RAS pathway degraders, with an emphasis on targeting RAS mutations as well as their upstream regulators and downstream effectors for potential cancer treatments.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"693-708"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel triazoloquinazoline derivatives as VEGFR inhibitors: synthesis, cytotoxic evaluation and in silico studies.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-01 Epub Date: 2025-02-25 DOI: 10.1080/17568919.2025.2468146

Reda R Mabrouk, Hazem A Mahdy, Abdallah E Abdallah, Ismail Celik, Abdelsalam Mohamed Abdelsalam Ouf, Mariam K Alamoudi, Aisha Alnami, Maged Mohammed Saleh Al Ward, Ahmed B M Mehany, Mohamed Ayman El-Zahabi

{"title":"Novel triazoloquinazoline derivatives as VEGFR inhibitors: synthesis, cytotoxic evaluation and in silico studies.","authors":"Reda R Mabrouk, Hazem A Mahdy, Abdallah E Abdallah, Ismail Celik, Abdelsalam Mohamed Abdelsalam Ouf, Mariam K Alamoudi, Aisha Alnami, Maged Mohammed Saleh Al Ward, Ahmed B M Mehany, Mohamed Ayman El-Zahabi","doi":"10.1080/17568919.2025.2468146","DOIUrl":"10.1080/17568919.2025.2468146","url":null,"abstract":"Background: New triazoloquinazoline derivatives were synthesized to explore their cytotoxic activity on various cancer cell lines, prompted by the need for effective anticancer agents.Research design and methods: All synthesized compounds were confirmed by spectroscopic methods and tested in vitro for their inhibitory activities against hepatocellular carcinoma (HepG-2), breast cancer (MCF-7), and prostate cancer (PC3) cell lines. Ten compounds were tested in vitro to explore their inhibitory activity against the VEGFR-2. Additionally, various studies were investigated for the most active compound 6, including cell cycle analysis, apoptotic activity assessment, effect on gene expression, safety profiling, molecular docking, MD simulation, and ADMET analysis.Results: Compounds 3a, 3c, and 6 exhibited higher cytotoxic activity against MCF-7 than doxorubicin. Compound 6 was most potent, arresting the cell cycle at G1 phase and showing proapoptotic action. It significantly inhibited VEGFR-2 and altered gene expression, promoting BAX, P21, and P53 while downregulating BCL-2. Docking and MD simulations indicated stable interaction with VEGFR-2, safety, and ADMET profiles suggested favorable drug-likeness and safety.Conclusions: Compound 6 has shown promising anticancer potential, particularly against breast cancer, but further research is needed to confirm these findings and address long-term safety.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"529-541"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Design, synthesis, and molecular docking studies of thiazole derivatives against phospholipase A₂ (Naja oxiana) venom.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-01 Epub Date: 2025-03-17 DOI: 10.1080/17568919.2025.2478807

Bibi F Nayyab, Muhammad Shah, Muhammad H H B Asad, Asma Zaidi, Fiaz Alam, Abdul Mannan, Umer Rashid

{"title":"Design, synthesis, and molecular docking studies of thiazole derivatives against phospholipase A2 (Naja oxiana) venom.","authors":"Bibi F Nayyab, Muhammad Shah, Muhammad H H B Asad, Asma Zaidi, Fiaz Alam, Abdul Mannan, Umer Rashid","doi":"10.1080/17568919.2025.2478807","DOIUrl":"10.1080/17568919.2025.2478807","url":null,"abstract":"Aim: Cobra venom phospholipase A2 (PLA2) has been known to induce life threatening effects post-envenomation in the victims. Being the most abundant and noxious component of snake venom, present study was envisaged to investigate new drug candidates against PLA2 enzyme.Methods: Amide and sulfonamide thiazole derivatives were synthesized and characterized using FTIR, 1HNMR and 13CNMR followed by docking targeted protein techniques. Furthermore, synthetic analogues were evaluated in vitro for their potentials to neutralize PLA2 activity.Results: Among the pool of synthetic derivatives, compound (7) (ethyl 2-(2-(4-isobutylphenyl)propanamido)thiazole-4-carboxylate) was found to be completely effective (p > 0.05; IC50 = 1 nM) to mask cent percent PLA2 activity. Moreover, Ramachandran plot further conferred about the location of amino acid residues in the most favored region and, therefore, attributed to confiscate PLA2 activity. Furthermore, ADME profile suggested that compound (7) possesses systemic bioavailability and efficacy with favorable safety profile (high solubility, membrane permeability, metabolic stability, and low potential for off-target results).Conclusion: Present study highlighted compound (7) as a potential PLA2 inhibitor to reverse PLA2-induced snake venom poisoning in future.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"659-667"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0