Future medicinal chemistry最新文献_第4页

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

Advancements in PROTAC-based therapies for neurodegenerative diseases.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-01 Epub Date: 2025-02-11 DOI: 10.1080/17568919.2025.2463310

Deyuan Kong, Liying Meng, Pengfei Lin, Guanzhao Wu

{"title":"Advancements in PROTAC-based therapies for neurodegenerative diseases.","authors":"Deyuan Kong, Liying Meng, Pengfei Lin, Guanzhao Wu","doi":"10.1080/17568919.2025.2463310","DOIUrl":"10.1080/17568919.2025.2463310","url":null,"abstract":"Neurodegenerative diseases are characterized by impairments in movement and cognitive functions. These disorders are frequently associated with the accumulation of misfolded protein aggregates, which present significant challenges for treatment with conventional small-molecule inhibitors. While FDA-approved amyloid-beta-directed antibodies, such as Lecanemab, have recently shown clinical success in modifying disease progression, there are currently no treatments capable of curing neurodegenerative diseases. Emerging technologies like proteolysis-targeting chimeras (PROTACs) offer additional promise by targeting disease-causing proteins for degradation, potentially opening new therapeutic avenues. Recent experiments have demonstrated that PROTACs can specifically target and degrade pathogenic proteins associated with neurodegenerative diseases, thereby offering potential therapeutic avenues. This review discusses the latest advances in employing PROTACs for treating neurodegenerative diseases and delves into the associated challenges and opportunities. Our goal is to provide researchers in drug development with new insights on creating novel PROTACs for therapeutic applications.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"591-605"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390703","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

A comprehensive insight into naphthalimides as novel structural skeleton of multitargeting promising antibiotics.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-01 Epub Date: 2025-02-16 DOI: 10.1080/17568919.2025.2463872

Lin-Li Mou, Xin-Miao Wu, Aisha Bibi, Jin-Xin Wang, Cheng-He Zhou

{"title":"A comprehensive insight into naphthalimides as novel structural skeleton of multitargeting promising antibiotics.","authors":"Lin-Li Mou, Xin-Miao Wu, Aisha Bibi, Jin-Xin Wang, Cheng-He Zhou","doi":"10.1080/17568919.2025.2463872","DOIUrl":"10.1080/17568919.2025.2463872","url":null,"abstract":"The globally growing antimicrobial resistance seriously threatens human health, increasing efforts have been devoting to the development of novel antibiotics. Naphthalimides contain a special skeleton of cyclic double imides and the naphthalene framework, this unique structure can exert multitargeting abilities which are helpful to overcome the escalating issue of resistance. Therefore, research in connection with the development of naphthalimides as novel antimicrobial agents is becoming progressively active. It has been revealed that naphthalimides as novel structural skeleton of multitargeting promising antibiotics could not only target DNAs and enzymes, disturb membrane, produce reactive oxygen species, etc. suggesting the multitargeting actions which do not induce resistance, but also show a broad antimicrobial spectrum with safety profile and pharmacokinetic characteristics, implying large potential as a new type of antibiotics via continuous efforts toward antimicrobial naphthalimides. This review presents naphthalimides as a new type of potential antimicrobial agents and discusses rational design strategies, structure-activity relationships, and mechanisms of action, with a comprehensive view to providing a new insight for in the rational design of efficient, broad-spectrum, and low-toxic naphthalimide antibiotics.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"575-590"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432817","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

Expecting medication misuse: a proactive approach to drug discovery to prevent fatal overdose.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-01 Epub Date: 2025-03-17 DOI: 10.1080/17568919.2025.2476388

Eileen Carry, Ariane Vasilatis, Anna Laroche Johnson, Jake William Ryan

{"title":"Expecting medication misuse: a proactive approach to drug discovery to prevent fatal overdose.","authors":"Eileen Carry, Ariane Vasilatis, Anna Laroche Johnson, Jake William Ryan","doi":"10.1080/17568919.2025.2476388","DOIUrl":"10.1080/17568919.2025.2476388","url":null,"abstract":"Misuse of central nervous system (CNS) depressants (alprazolam, fentanyl, etc.) is a major cause of fatal overdose, with a high prevalence of deaths involving polydrug interactions from the victim's own prescriptions. Thus, there is an urgent need to improve the safety of CNS depressants to prevent fatalities. Pharmacological pursuits aiming to prevent harm through the design of non-addictive alternatives have either failed before clinical trials or produced mediocre treatment alternatives. Therefore, we propose a new perspective for medicinal chemists: rather than aiming to prevent misuse, we must design new central nervous system (CNS) depressants under the expectation of misuse. By shifting the design focus to partial modulators rather than full agonists, we can develop novel chemical entities (NCEs) that intrinsically minimize physical harm caused by misuse without sacrificing therapeutic efficacy. In this perspective, we provide an overview of the two most widely misused classes of medications (opioid and GABAA receptor modulators) in relation to pharmacodynamic properties and clinical outcomes. We then suggest a drug discovery pathway focused on physiological parameters. It is our opinion that this approach would dramatically decrease the lethality of overdose and improve outcomes of treatments for pain, anxiety, and withdrawal from alcohol, benzodiazepines, and opioids.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"681-692"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647987","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

How does machine learning augment alchemical binding free energy calculations?

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-01 Epub Date: 2025-02-08 DOI: 10.1080/17568919.2025.2463870

Ingo Muegge, Yunhui Ge

引用次数: 0

Synergistic anti-inflammatory and anti-tb effects of Au-Pt-Cu nanofluids: experimental and computational insights.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-01 Epub Date: 2025-03-21 DOI: 10.1080/17568919.2025.2478818

Amit Dubey, Manish Kumar, Amer M Alanazi, Aisha Tufail, Abhay D Bagul

引用次数: 0

Key targets for small molecule drugs on the IGF1 signaling pathway.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-02-20 DOI: 10.1080/17568919.2025.2470105

Haim Werner

引用次数: 0

The versatility of phenothiazines as an anticancer drug scaffold. 吩噻嗪作为抗癌药物支架的多功能性。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-02-01 Epub Date: 2025-01-19 DOI: 10.1080/17568919.2025.2453417

Arun Kumar, Deepak Kumar

引用次数: 0

Pharmaceutical technological trends containing flavonoids: a patent review. 含黄酮类化合物的制药技术趋势：专利回顾。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-02-01 Epub Date: 2025-01-21 DOI: 10.1080/17568919.2025.2453408

Ana Maria Santos Oliveira, Anamaria Mendonça Santos, José Adão Carvalho Nascimento Júnior, Cláudio Carvalho Santana Júnior, João Rafael Lisboa Rego Brito, Jussara Secundo Dos Santos, Saravanan Shanmugam, Paula Dos Passos Menezes, Luiza Abrahão Frank, Mairim Russo Serafini

{"title":"Pharmaceutical technological trends containing flavonoids: a patent review.","authors":"Ana Maria Santos Oliveira, Anamaria Mendonça Santos, José Adão Carvalho Nascimento Júnior, Cláudio Carvalho Santana Júnior, João Rafael Lisboa Rego Brito, Jussara Secundo Dos Santos, Saravanan Shanmugam, Paula Dos Passos Menezes, Luiza Abrahão Frank, Mairim Russo Serafini","doi":"10.1080/17568919.2025.2453408","DOIUrl":"10.1080/17568919.2025.2453408","url":null,"abstract":"Flavonoids such as silibinin, hesperetin, and phloretin exhibit well-documented biological activities, including anti-inflammatory, cytoprotective, anticarcinogenic, and antioxidant effects. However, their clinical application remains limited due to challenges such as poor aqueous solubility, low bioavailability, and restricted intestinal absorption, which can significantly reduce their pharmacological efficacy. This review analyzed patents related to innovative pharmaceutical technologies for flavonoids. The analysis used databases from the World Intellectual Property Organization and the European Patent Office. Following a comprehensive screening process, 38 patents were selected for detailed examination. These patents highlighted numerous studies on novel formulations, characterizations, and proprietary conditions. This review highlights technologies, such as nanocapsules, nanoemulsions, solid dispersions, phospholipid carriers, inclusion complexes, microemulsions, and other advanced systems, which enhance bioactive molecules' water solubility and stability. Consequently, these technologies improve permeability and absorption through the intended administration route, demonstrating the potential of flavonoids as promising candidates for various treatments, particularly when integrated into pharmaceutical technologies.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"363-379"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003325","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

A series of benzensulfonamide derivatives as new potent carbonic anhydrase IX and XII inhibitors.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-02-01 Epub Date: 2025-01-29 DOI: 10.1080/17568919.2025.2453420

Susanna Nencetti, Doretta Cuffaro, Lidia Ciccone, Alessio Nocentini, Miriana Di Stefano, Giulio Poli, Marco Macchia, Tiziano Tuccinardi, Elisa Nuti, Claudiu T Supuran, Armando Rossello, Elisabetta Orlandini

{"title":"A series of benzensulfonamide derivatives as new potent carbonic anhydrase IX and XII inhibitors.","authors":"Susanna Nencetti, Doretta Cuffaro, Lidia Ciccone, Alessio Nocentini, Miriana Di Stefano, Giulio Poli, Marco Macchia, Tiziano Tuccinardi, Elisa Nuti, Claudiu T Supuran, Armando Rossello, Elisabetta Orlandini","doi":"10.1080/17568919.2025.2453420","DOIUrl":"10.1080/17568919.2025.2453420","url":null,"abstract":"Aim: Human carbonic anhydrases (hCAs) are involved in many physiological processes including respiration, pH control, ion transport, bone resorption, and gastric fluid secretion. Recently, CA IX and CA XII have been studied for their role in cancer diseases, motivating the design of inhibitors of these isoforms.Material and method: Here, we used the tail approach to design a new series of monoaryl (1a-i) and bicyclic (1j-n) benzensulfonamide derivatives CA IX and CA XII inhibitors. All synthesized compounds were investigated toward a panel of hCAs, and most of them exhibited potent CA inhibitory activity for CA II, CA IX and CA XII with Ki values. In silico studies were performed to investigate the binding mode between inhibitors and CA.Results and conclusion: The best compound was 1i that showed a low nanomolar range of Ki value as CA inhibitor (Ki = 9.4, 5.6 and 6.3 nM hCA II, IX and XII, respectively).","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"271-285"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058210","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