Future medicinal chemistry最新文献_第7页

Exploring digestive enzymes' differential affectivity of synthesized 2-thienyl-based chalcones. 探索消化酶对合成的2-噻吩基查尔酮的差异性影响。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-07-01 Epub Date: 2025-07-04 DOI: 10.1080/17568919.2025.2527583

Prabhjot Kaur, Urmila Berar, Neera Raghav

{"title":"Exploring digestive enzymes' differential affectivity of synthesized 2-thienyl-based chalcones.","authors":"Prabhjot Kaur, Urmila Berar, Neera Raghav","doi":"10.1080/17568919.2025.2527583","DOIUrl":"10.1080/17568919.2025.2527583","url":null,"abstract":"Aim: This study aimed to synthesize thiophene-based chalcones using green and conventional methods and evaluate their modulatory effects on key digestive enzymes-α-amylase, lipase, and trypsin for potential therapeutic applications in metabolic disorders.Materials & methods: A series of twenty 2-acetylthiophene-based chalcones were synthesized via Claisen-Schmidt condensation using conventional, grinding, and ultrasonication methods. The compounds were characterized using FTIR, NMR, and melting point analysis. In vitro enzyme assays were conducted to assess activity against α-amylase, lipase, and trypsin. Molecular docking, drug-likeness, and ADMET profiling were performed in silico to predict binding interactions and pharmacokinetic properties.Results: Ultrasonication offered the highest yield in the shortest time. Chalcones inhibited lipase (40.18-74.23%) and trypsin (40.86-73.91%), with compounds 3q and 3r showing the strongest inhibition (IC₅₀ = 1.25 × 10-8 M and 1.17 × 10-8 M, respectively). Unexpectedly, α-amylase activation (50.18-75.18%) was observed, with compound 3g being the most effective. Docking studies supported enzyme binding, and ADMET analysis confirmed favorable safety profiles.Conclusions: Thiophene-based chalcones exhibit promising digestive enzyme modulatory properties, particularly as lipase and trypsin inhibitors, with potential application in managing obesity and related metabolic disorders.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1535-1545"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559766","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

Overcoming translational barriers in RNA-protein docking: enhancing computational accuracy for targeted drug discovery. 克服rna -蛋白对接中的翻译障碍：提高靶向药物发现的计算准确性。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-07-01 Epub Date: 2025-07-18 DOI: 10.1080/17568919.2025.2533061

Habiba Akram, Muneeb Ur Rahman, Sharjeel Mazhar, Farheen Qamer, Ayesha Yousaf

{"title":"Overcoming translational barriers in RNA-protein docking: enhancing computational accuracy for targeted drug discovery.","authors":"Habiba Akram, Muneeb Ur Rahman, Sharjeel Mazhar, Farheen Qamer, Ayesha Yousaf","doi":"10.1080/17568919.2025.2533061","DOIUrl":"10.1080/17568919.2025.2533061","url":null,"abstract":"RNA-protein interactions can play a crucial role in the regulation of gene expression, cellular processes, and progression of diseases, thus making them one of the major targets for drug discovery. Although knowledge of these complex interactions remains limited, owing to less structural resolution data, computational, and translational challenges. The review overviews the evolution of advanced computational docking tools and recent cutting-edge innovations in RNA-protein interaction research, by highlighting advanced and highly precise approaches such as cryo-electron microscopy (cryo-EM), nuclear magnetic resonance (NMR) spectroscopy, and novel molecular docking models like DiffDock. Furthermore, the integration of multi-omics data and machine learning approaches in drug discovery not only improves precision but also the speed and efficiency of docking, thus highlighting the dynamic and highly complex nature of RNA molecules. The major translational hurdles that limit the bridging between computational predictions and clinical applications are also highlighted, thus demanding more interdisciplinary collaborations to achieve the desired biomolecular targets. By emphasizing computational modeling, structural biology, clinical pharmacology, and translational barriers in RNA-protein docking, the article provides a comprehensive framework to speed up the highly specific, accurate, and precise drug discovery of novel therapeutics targeting RNA-protein interactions.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1623-1640"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658887","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

Progress and challenges in the development of clinically viable Piezo1 inhibitors. 临床可行的Piezo1抑制剂的发展进展和挑战。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-07-01 Epub Date: 2025-07-11 DOI: 10.1080/17568919.2025.2532996

Daniel Baecker

引用次数: 0

Benzimidazole derivatives as potent α-amylase inhibitors: synthesis, characterization and in vitro α-amylase inhibition. 苯并咪唑衍生物α-淀粉酶抑制剂：合成、表征及体外α-淀粉酶抑制作用。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-07-01 Epub Date: 2025-07-16 DOI: 10.1080/17568919.2025.2527585

Shantaben K Kangad, Sachin M Sitapara, Deepika Maliwal, Chintan Somaiya, Raghuvir R S Pissurlenkar, V N Patolia

{"title":"Benzimidazole derivatives as potent α-amylase inhibitors: synthesis, characterization and in vitro α-amylase inhibition.","authors":"Shantaben K Kangad, Sachin M Sitapara, Deepika Maliwal, Chintan Somaiya, Raghuvir R S Pissurlenkar, V N Patolia","doi":"10.1080/17568919.2025.2527585","DOIUrl":"10.1080/17568919.2025.2527585","url":null,"abstract":"Aim: This study aims to evaluate the α-amylase inhibitory potential of newly synthesized benzimidazole derivatives, assessing their viability as prospective antidiabetic agents.Materials & methods: A series of 2-(4-(1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-N-phenylacetamide derivatives (7a-7j) were synthesized via an efficient synthetic route. The structural elucidation of these compounds was accomplished using advanced spectroscopic techniques, including mass spectrometry, FT-IR, 1H & 13C NMR, and elemental analysis. The α-amylase inhibitory activity of the synthesized compounds was evaluated in vitro, with IC₅₀ values determined to quantify their efficacy. To gain insights into the molecular interactions, molecular docking studies were conducted, followed by extensive molecular dynamics (MD) simulations.Result & discussion: All synthesized derivatives exhibited varying degrees of α-amylase inhibitory activity, with IC₅₀ values ranging from 1.10 ± 0.05 to 12.50 ± 0.30 μM. Notably, compounds 7b, 7c, and 7i demonstrated superior inhibitory effects, with IC₅₀ values of 1.20 ± 0.05, 1.40 ± 0.10, and 1.10 ± 0.05 μM, respectively, surpassing the standard drug acarbose (IC₅₀ = 1.70 ± 0.10 μM).Conclusion: The synthesized benzimidazole derivatives, notably compounds 7b, 7c, and 7i, demonstrated potent α-amylase inhibitory activity, surpassing the standard drug acarbose. These findings highlight their potential as lead compounds for developing novel antidiabetic agents.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1521-1533"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642216","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

Green synthesis, in vitro, and in silico assessments of hydrazone-Schiff bases as potential antileishmanial agents. 作为潜在抗利什曼原虫药物的腙希夫碱的绿色合成、体外和计算机评价。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-07-01 Epub Date: 2025-07-16 DOI: 10.1080/17568919.2025.2533114

Sadia Khan, Sher Wali Khan, Momin Khan, Saira Nayab, Muhammad Naveed Umar, Syed Wadood Ali Shah, Haroon Ur Rashid

{"title":"Green synthesis, in vitro, and in silico assessments of hydrazone-Schiff bases as potential antileishmanial agents.","authors":"Sadia Khan, Sher Wali Khan, Momin Khan, Saira Nayab, Muhammad Naveed Umar, Syed Wadood Ali Shah, Haroon Ur Rashid","doi":"10.1080/17568919.2025.2533114","DOIUrl":"10.1080/17568919.2025.2533114","url":null,"abstract":"Aims: To synthesize and assess hydrazone Schiff bases using green chemistry principles for potential antileishmanial activity.Materials & methods: Sixteen hydrazone Schiff bases, including seven novel compounds (SSB2, SSB4, SSB5, RSB4, SSB14, SSB15, and SSB31), were synthesized under solvent-free conditions using grinding technique. The compounds were structurally confirmed via FT-IR, 1 H NMR, and 1 3 C NMR spectroscopy. Their in vitro antileishmanial activities were evaluated versus Leishmania tropica promastigotes and amastigotes. Molecular docking studies targeted leishmanolysin enzyme, while Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) and Density Functional Theory (DFT) analyses were used to predict pharmacokinetics, drug-likeness and stability.Results: Most compounds showed moderate to good activity, with SSB28, SSB35, SSB36, and RSB4 displaying IC₅₀ values between 4 ± 0.5 and 8.0 ± 0.2 µg/mL. SSB28 was the most potent, with its IC₅₀ values of 4 ± 0.5 and 4.5 ± 0.4 µg/mL versus Promastigote and amastigote respectively as compared to the reference drug Amphotericin-B (IC50 2.0 and 2.3 ± 0.5 µg/mL). Docking studies indicated strong binding of SSB28 to leishmanolysin. ADMET and DFT results showed that SSB28 possesses favorable pharmacokinetics and low predicted toxicity.Conclusions: SSB28 is an encouraging antileishmanial lead derivative with potent activity, environmental compatibility, and predicted safety making it a feasible candidate for further drug development.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1641-1657"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649075","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

Anti-adhesive glycoconjugates against Candida albicans: effect of the aromatic substituents in anti-fungal activity. 抗白色念珠菌黏附糖缀合物：芳香取代基在抗真菌活性中的作用。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-07-01 Epub Date: 2025-08-08 DOI: 10.1080/17568919.2025.2540274

Keela Kessie, Kyle Doherty, Laia Moreno, Diana Bura, Cristina Trujillo, Kevin Kavanagh, Trinidad Velasco-Torrijos

{"title":"Anti-adhesive glycoconjugates against Candida albicans: effect of the aromatic substituents in anti-fungal activity.","authors":"Keela Kessie, Kyle Doherty, Laia Moreno, Diana Bura, Cristina Trujillo, Kevin Kavanagh, Trinidad Velasco-Torrijos","doi":"10.1080/17568919.2025.2540274","DOIUrl":"10.1080/17568919.2025.2540274","url":null,"abstract":"Aims: To explore novel anti-virulence strategies against Candida albicans by evaluating the structure-activity relationship (SAR) of aromatic glycoconjugates that inhibit fungal adhesion to buccal epithelial cells (BECs), focusing on the effect of the substituents on the aromatic ring.Materials & methods: A series of aromatic glycoconjugates containing divalent β-D-galactopyranosyl-1,2,3-triazol-4-ylmethylamide motif, important for anti-adhesion activity, were synthesized and assessed as inhibitors of C. albicans adhesion to BECs. The impact of various aromatic substituents on anti-adhesion activity was systematically analyzed. Conformational studies were conducted to investigate the spatial orientation of galactose moieties in active compounds.Results: Glycoconjugates with less sterically hindered and more lipophilic aromatic substituents, such as cyclopropyl groups, demonstrated enhanced inhibition of C. albicans adhesion. Conformational analysis revealed that the most active compounds consistently adopted a \"closed\" orientation of the galactose moieties, regardless of the nature of the aromatic substituent.Conclusions: Aromatic glycoconjugates with specific structural features, particularly lipophilic and compact substituents, show promise as anti-adhesion agents against C. albicans. These findings support the potential of anti-virulence strategies targeting fungal adhesion as alternatives to traditional fungicidal therapies.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1659-1674"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798612","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

Ribonucleotide reductase (RNR) inhibitors as target-based weapon for future cancer drug development. 核糖核苷酸还原酶（RNR）抑制剂作为未来癌症药物开发的靶向武器。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-07-01 Epub Date: 2025-07-04 DOI: 10.1080/17568919.2025.2527596

Jaykumar Nagapara, Bimalkumar Patel, Bhargav Devliya, ShreyaJ Chauhan, Hitesh D Patel

{"title":"Ribonucleotide reductase (RNR) inhibitors as target-based weapon for future cancer drug development.","authors":"Jaykumar Nagapara, Bimalkumar Patel, Bhargav Devliya, ShreyaJ Chauhan, Hitesh D Patel","doi":"10.1080/17568919.2025.2527596","DOIUrl":"10.1080/17568919.2025.2527596","url":null,"abstract":"Cancer remains one of the leading causes of mortality worldwide, necessitating the development of precise and effective therapeutic strategies. Targeted cancer therapies aim to enhance treatment specificity while minimizing adverse effects. Ribonucleotide reductase (RNR), a key enzyme in Deoxyribonucleic acid (DNA) synthesis and cell division, has emerged as a critical target in cancer research. By inhibiting RNR, the production of deoxyribonucleotides is disrupted, ultimately impeding DNA replication and halting cancer cell proliferation. Given its essential role in cell cycle regulation, RNR inhibition represents a promising approach for anticancer therapy. This review highlights recent advances in the synthesis and biological evaluation of RNR inhibitors, emphasizing their potential as precision-targeted therapeutics. Furthermore, computational insights into their mechanism of action provide a foundation for designing next-generation inhibitors with enhanced potency and selectivity, paving the way for future pharmaceutical developments.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1601-1622"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564734","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

The current landscape of quinazoline derivatives with in vivo anticancer therapeutic potential-part II. 具有体内抗癌治疗潜力的喹唑啉衍生物的现状-第二部分。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-07-01 Epub Date: 2025-07-30 DOI: 10.1080/17568919.2025.2539670

Shanshan Huang, Zhi Xu, Yan Zhang, Jialin Zhu, Wenjun Zhou

{"title":"The current landscape of quinazoline derivatives with in vivo anticancer therapeutic potential-part II.","authors":"Shanshan Huang, Zhi Xu, Yan Zhang, Jialin Zhu, Wenjun Zhou","doi":"10.1080/17568919.2025.2539670","DOIUrl":"10.1080/17568919.2025.2539670","url":null,"abstract":"Cancer, which can invade and metastasize to almost all organs or tissues, is one of the deadliest diseases across the world. Drug resistance, especially multidrug resistance, is a principal obstacle to effective therapeutic interventions against cancer, creating an urgent demand for the exploration of novel anticancer chemotherapeutics. Quinazoline derivatives are useful templates for exploring new anticancer chemotherapeutics due to their ability to exert anticancer effects through various mechanisms, mainly associated with alterations in cell cycle progression, induction of apoptosis, and modification of autophagy. Moreover, tens of quinazoline-based agents have already been approved for cancer therapy, occupying a prominent place in the current therapeutic arsenal. This review provides an overview of the current status of quinazoline derivatives that hold in vivo anticancer therapeutic potential, along with their mechanisms of action, toxicity profiles, and pharmacokinetic characteristics, encompassing literature published from 2015 to the present.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1771-1786"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741844","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, anti-breast cancer and in silico studies of substituted triphenyl imidazole-N-alkyl linked indole derivatives. 取代三苯基咪唑- n -烷基连接吲哚衍生物的设计、合成、抗乳腺癌和硅研究。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-07-01 Epub Date: 2025-08-04 DOI: 10.1080/17568919.2025.2539673

Arun Kumar, Sounok Sengupta, Ashok Kumar Yadav, Raman Preet Singh, Tripti Sinha, Pratiti Bhattacharjee, Biswarup Basu, G Marriapan, Sanjib Bhattacharyya, Deepak Kumar

{"title":"Design, synthesis, anti-breast cancer and in silico studies of substituted triphenyl imidazole-N-alkyl linked indole derivatives.","authors":"Arun Kumar, Sounok Sengupta, Ashok Kumar Yadav, Raman Preet Singh, Tripti Sinha, Pratiti Bhattacharjee, Biswarup Basu, G Marriapan, Sanjib Bhattacharyya, Deepak Kumar","doi":"10.1080/17568919.2025.2539673","DOIUrl":"10.1080/17568919.2025.2539673","url":null,"abstract":"Aim: Cancer is an affliction on societies worldwide, chemotherapy, though effective, has its limitations, indicating the need for new therapeutic agents. Imidazole and indole are two important bioactive heterocycles important for developing newer anticancer molecules.We synthesized a series of substituted imidazole-linked indole derivatives and evaluated them for anticancer activity on MCF-7 cells. Further in silico, cell cycle and apoptosis studies was done for the most active compounds.Materials and methods: Compounds were synthesized by preparing substituted triphenyl imidazoles from benzaldehydes and were further linked to indoles using N-chloroalkyl indoles. The synthesized compounds were characterized and tested for anticancer activity using MTT-assay on MCF-7 cells, followed by a cell-cycle and apoptosis assay of most active compound using flow cytometry. The most active compound was subjected to docking studies using PyRx with the EGFR protein 4HJO, followed by a molecular dynamics simulation using Desmond. Finally, DFT calculations were performed using ORCA 6.0 followed by QSAR analysis of the compounds.Results: Compounds were confirmed by 1H NMR, 13C NMR, mass spectroscopy, and showed IC50 values of 26.52 to 39.05 µM on MCF-7 cells. The most active compound 11i produced apoptosis at its IC50 in MCF-7 cells and arrested the cell cycle in G2/M phase. 11i also had good interactions with 4HJO which confirmed its stability in both molecular dynamics and DFT studies. QSAR studies predicted the relevant structural features for the biological activity.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1675-1692"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775054","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

Small-molecule Cathepsin K inhibitors: a medicinal chemistry perspective. 小分子组织蛋白酶K抑制剂：药物化学的观点。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-07-01 Epub Date: 2025-08-05 DOI: 10.1080/17568919.2025.2542717

Xuan Guan, Shu Cheng, Yifei Yin, Shufang Du

引用次数: 0