Future medicinal chemistry最新文献

{"title":"Design and synthesis of thiadiazoles as anticancer, apoptotic, and VEGFR-2 inhibitors.","authors":"Walid E Elgammal, Hazem Elkady, Mohammed A Dahab, Hazem A Mahdy, Mohamed Hagras, Ahmed Nofal, Bshra A Alsfouk, Eslam B Elkaeed, Ibrahim H Eissa, Ahmed M Metwaly","doi":"10.1080/17568919.2025.2485863","DOIUrl":"https://doi.org/10.1080/17568919.2025.2485863","url":null,"abstract":"<p><strong>Background: </strong>Vascular endothelial growth factor receptor (VEGFR-2) inhibitors are critical in cancer therapy due to their role in suppressing tumor angiogenesis. Herein, we report a new series of thiadiazole-based derivatives as potential VEGFR-2 inhibitors with promising anticancer activity.</p><p><strong>Methods: </strong>The synthesized compounds were evaluated for anti-proliferative activity against human cancer cell lines (HCT-116, MCF-7, and HepG-2), and WI-38 as normal cells. Sorafenib was used as a reference drug. VEGFR-2 inhibitory activity was determined, followed by cell cycle analysis, apoptosis assays, Q-RT-PCR analysis, and wound-healing assays. <i>In silico</i> molecular docking was conducted to explore binding interactions.</p><p><strong>Results: </strong>Among the tested compounds, <b>13b</b> exhibited potent anti-proliferative activity (IC₅₀: 3.98-11.81 µM) and strong VEGFR-2 inhibition (IC₅₀: 41.51 nM), surpassing sorafenib (IC₅₀: 53.32 nM). Cell cycle analysis revealed that <b>13b</b> induced G2/M phase arrest in MCF-7 cells. Apoptosis levels increased from 2% to 52%, accompanied by a > 12-fold rise in the Bax/Bcl-2 ratio and activation of caspase-8/9. Additionally, <b>13b</b> significantly suppressed MCF-7 cell migration, with only 5.28% wound closure. <i>In silico</i> studies confirmed its strong VEGFR-2 binding interactions.</p><p><strong>Conclusion: </strong>Thiadiazole-based derivatives, particularly compound <b>13b</b>, exhibit potent VEGFR-2 inhibition, anti-proliferative effects, apoptosis induction, and anti-migratory activity, supporting their potential as promising anticancer agents.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-13"},"PeriodicalIF":3.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of <i>bis</i>-chalcones and <i>bis</i>-pyrimidines as potential urease inhibitors: from synthesis to computational insights.","authors":"Nafeesa Naeem, Sumera Zaib, Ehsan Ullah Mughal, Gehan Ahmed Othman, Amina Sadiq, Nehal Rana","doi":"10.1080/17568919.2025.2485870","DOIUrl":"https://doi.org/10.1080/17568919.2025.2485870","url":null,"abstract":"<p><strong>Aims: </strong>This study focuses on the design and evaluation of <i>bis</i>-chalcones and <i>bis</i>-pyrimidines as potential urease inhibitors.</p><p><strong>Materials and methods: </strong>A series of <i>bis</i>-chalcone and <i>bis</i>-pyrimidine derivatives were synthesized and assessed for their <i>in vitro</i> urease inhibitory activity. Kinetic studies were conducted using Lineweaver-Burk plots to determine the inhibition mechanism of the most potent compound. Molecular docking was employed to investigate the binding interactions with the urease active site, followed by MD simulations to validate complex stability. Computational ADMET analysis was performed to assess the drug-like properties of the most active inhibitor.</p><p><strong>Results: </strong>Several synthesized compounds exhibited potent urease inhibitory activity, significantly surpassing the standard inhibitor thiourea. The most active compound, 8P, displayed noncompetitive inhibition, as confirmed by kinetic studies. SAR analysis revealed that electron-withdrawing substituents enhanced inhibitory potency. Molecular docking studies demonstrated favorable interactions between inhibitors and key urease residues, while MD simulations confirmed complex stability. ADMET analysis supported the drug-like potential of 8P.</p><p><strong>Conclusions: </strong>This study provides valuable insights into the development of target compounds as promising urease inhibitors. These findings suggest their potential therapeutic applications for urease-related disorders.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-13"},"PeriodicalIF":3.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methoxy group: a non-lipophilic \"scout\" for protein pocket finding.","authors":"Debora Chiodi, Yoshihiro Ishihara","doi":"10.1080/17568919.2025.2485865","DOIUrl":"https://doi.org/10.1080/17568919.2025.2485865","url":null,"abstract":"","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-3"},"PeriodicalIF":3.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of 5-phenylnitro bearing furan-based chalcones as a new class of potent MAO-B inhibitors.","authors":"Kadeeja Thottungal Kalathil, Bishnu Prasad Pandey, Arshida Thottile Peedikayil, Raihan Arikkattel Abdu, Rajasree Raghavan Sreekumari, Alanoud T Alfagham, Abdallah M Elgorban, Sunil Kumar, Hoon Kim, Sanal Dev, Bijo Mathew","doi":"10.1080/17568919.2025.2485671","DOIUrl":"https://doi.org/10.1080/17568919.2025.2485671","url":null,"abstract":"<p><strong>Aim: </strong>The purpose is to synthesize a new class of furan-based chalcone compounds (KD1-KD14) and to investigate their monoamine oxidase (MAO)-A and -B inhibitory activities.</p><p><strong>Material and method: </strong>The 14 chalcones were synthesized using an open mortar and pestle. Lead molecules were screened via inhibitory activity, BBB permeability, and computation studies.</p><p><strong>Results: </strong>Most of the tested compounds showed promising activity for MAO-B over than MAO-A. Among the molecules, KD1 and KD9 revealed the significant inhibitory potentials toward MAO-B with IC₅₀ values of 0.023 ± 0.004 and 0.015 ± 0.001 µM, respectively, and with high selectivity indices of 723.04 and >2666.66, respectively, over MAO-A. Further, kinetics and reversibility test revealed that both KD1 and KD9 were competitive reversible MAO-B inhibitors with K_i values of 13.5 ± 4.95 and 6.15 ± 0.92 nM, respectively. Additionally, the PAMPA test showed that both KD1 and KD9 compounds permeated the central nervous system. Furthermore, molecular docking and dynamics simulations showed that both the chemicals formed pi-cation and hydrogen bonds with the MAO-B pocket and stabilized the MAO-B over the course of a 100 ns simulation.</p><p><strong>Conclusion: </strong>Our results revealed that KD1 and KD9 are potent selective, reversible, and competitive MAO-B inhibitors.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-9"},"PeriodicalIF":3.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison between conventional, grinding, and microwave synthesis of methylpyrazoles as VEGFR-2/HSP90 dual inhibitors.","authors":"Ebtehal M Husseiny, Rana M Abdelnaby, Najla Altwaijry, Asmaa Saleh, Kurls E Anwer","doi":"10.1080/17568919.2025.2485866","DOIUrl":"10.1080/17568919.2025.2485866","url":null,"abstract":"<p><strong>Aim: </strong>Embracing structure extension and substitution variation, methylpyrazolones <b>2-6</b> and dimethylpyrazoles <b>8-14</b> were synthesized as VEGFR-2/HSP90 dual inhibitors.</p><p><strong>Materials and methods: </strong>The eco-friendly synthesis of the desired analogs was performed by conventional, grinding, and microwave-assisted methods.</p><p><strong>Results: </strong>All entities have been tested for their antitumor action against three carcinomas, whereas compounds <b>6, 12</b>, and <b>13</b> showed significant cytotoxicity and selectivity toward the examined carcinomas. The consecutive molecular mechanistic studies proved that <b>6</b> and <b>12</b> exhibited dual inhibition of VEGFR-2 and HSP90 and prompted MCF-7 cycle arrest at G2/M phase followed by apoptosis stimulation.</p><p><strong>Conclusion: </strong>Molecular docking revealed strong interaction between the potent analogs and VEGFR-2/HSP90 active sites inspiring these congeners to be potential drug candidates in cancer treatment.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-15"},"PeriodicalIF":3.2,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of indole hybrids for potential lung cancer treatment - part II.","authors":"Shanshan Huang, Zhi Xu, Yafei Zhuang","doi":"10.1080/17568919.2025.2485867","DOIUrl":"https://doi.org/10.1080/17568919.2025.2485867","url":null,"abstract":"<p><p>Lung cancer has become the most prevalent cancer for the past three decades, and the 5-years survival rate of lung cancer is only ~20% nowadays. Chemotherapy is the mainstay of lung cancer therapy, especially for non-small cell lung cancer. However, drug resistance represents a principal cause of therapeutic failure in non-small cell lung cancer leading to therapeutic insensitivity, tumor recurrence, and disease progression. Indole hybrids have the potential to conquer drug resistance, enhance efficacy, reduce adverse events, and improve pharmacokinetic properties due to their capacity to inhibit multiple targets simultaneously. Moreover, indole hybrids osimertinib, mobocertinib, cediranib, and vizimpro are currently applied in clinics for lung cancer therapy, demonstrating that indole hybrids are valuable scaffolds in the treatment and eradication of lung cancer. This review provides a comprehensive overview of the evolving landscape of indole hybrids with the in vitro and in vivo efficacy against lung cancer, and the structure-activity relationships as well as mechanisms of action are also discussed, covering articles published from 2021 onward.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-17"},"PeriodicalIF":3.2,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of indole hybrids for potential lung cancer treatment-part I: nitrogen-containing six-membered aromatic heterocycles.","authors":"Shijia Zhao, Zhi Xu","doi":"10.1080/17568919.2025.2485675","DOIUrl":"10.1080/17568919.2025.2485675","url":null,"abstract":"<p><p>Lung cancer is the most prevalent invasive malignancy and the leading cause of cancer-related death. Chemotherapy is vital for lung cancer therapy, but multidrug resistance is responsible for the majority of lung cancer fatalities, creating an imperative demand to develop novel chemotherapeutics. Indole is a valuable anti-lung cancer pharmacophore since its derivatives could act on lung cancer cells through various mechanisms. Notably, indole hybrids could inhibit multiple targets simultaneously and have the potential to overcome the shortcomings of traditional chemotherapeutics. Moreover, many indole hybrids such as the indole-pyrimidine hybrid osimertinib and the indole-hydroxamic acid hybrid panobinostat, are either under clinical evaluations or have already been approved for lung cancer therapy. This indicates that the rational design of indole hybrids represents a highly prospective approach for the development of new anti-lung cancer chemotherapeutic agents. This review focuses on exploring the anti-lung cancer therapeutic potential of indole hybrids and delves into their action mechanisms as well as structure-activity correlations, covering articles published between 2021 and present. The ultimate goal is to offer a foundation for the rational design of indole hybrids in the future.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-17"},"PeriodicalIF":3.2,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zn (II) complex with vanillin derived Schiff base: antifungal, antibacterial, antioxidant and anticholinesterase activities.","authors":"Solange de Oliveira Pinheiro, Jordana Lima Braga, Wildson Max Barbosa da Silva, Guida Hellen Mota Do Nascimento, Renato Almeida Montes, Daniela Ribeiro Alves, Daniel Sampaio Rodrigues, Amanda Cavalcante Leitão, Vitória Pessoa de Farias Cabral, Lara Elloyse Almeida Moreira, Lívia Gurgel Do Amaral Valente Sá, Cecília Rocha da Silva, João Batista de Andrade Neto, Kirley Marques Canuto, Selene Maia de Morais, Hélio Vitoriano Nobre Júnior","doi":"10.1080/17568919.2025.2479421","DOIUrl":"https://doi.org/10.1080/17568919.2025.2479421","url":null,"abstract":"<p><strong>Aim: </strong>To synthesize and characterize a Schiff base derived from vanillin and tris(hydroxymethyl)aminomethane (VTRIS) and the Zinc (II) complex [Zn(VTRIS)₂](CH₃COO)₂.</p><p><strong>Materials and methods: </strong>VTRIS and the Zn (II) complex were synthesized through condensation and complexation reactions, respectively. Structures were confirmed by electron spectroscopy in the UV-Vis, FT-IR and NMR regions. Toxicity was evaluated in Artemia salina, antimicrobial activity was evaluated by microdilution assay, ABTS and DPPH methods were used for antioxidant effect and the anticholinesterase potential was investigated.</p><p><strong>Results: </strong>VTRIS and the complex showed low toxicity in <i>Artemia salina</i> (LC₅₀ = 698.56 and 543.88, respectively). VTRIS did not show antifungal or antibacterial activity, but the complex showed MICs ranging from 32 to 128 μg/mL against <i>Cryptococcus neoformans</i> and <i>Candida</i> spp. and 512 μg/mL against <i>Staphylococcus aureus</i>, demonstrating an antimicrobial effect improvement after coordination to the metal center. VTRIS and the complex showed excellent results as antioxidant molecules, and the complex presented lower values than the standard quercetin in the ABTS method (IC₅₀ = 1.08 and 1.63 μg/mL, respectively). VTRIS and the complex showed anticholinesterase potential of 1.93 and 1.83 μg/mL.</p><p><strong>Conclusion: </strong>Zn complexation potentiates VTRIS, and this compound exhibits promising antimicrobial, antioxidant, and anticholinesterase activities at nontoxic concentrations.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-12"},"PeriodicalIF":3.2,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spirocyclic compounds: potential drug leads in the fight against <i>Mycobacterium tuberculosis</i>.","authors":"Pardeep Kumar, Anuradha Singampalli, Rani Bandela, Bellapukonda Srimounika, Sugali Indravath Rajyalakshmi, Ankita Devi, Srinivas Nanduri, Yaddanapudi Venkata Madhavi","doi":"10.1080/17568919.2025.2479413","DOIUrl":"https://doi.org/10.1080/17568919.2025.2479413","url":null,"abstract":"<p><p>TB drug discovery needs scientists' attention since drug resistance in TB, including extensively drug-resistant TB (XDR-TB) and multidrug-resistant TB (MDR-TB), is a major healthcare concern. Since millions of fatalities from tuberculosis are recorded each year, there is an urgent need to discover new anti-tubercular medications that will either eradicate or control the disease. Spiro compounds have garnered a lot of attention in medicinal chemistry these days because of various biological activities mainly because of their adaptability and structural resemblance to significant pharmacophores. This article overviews the synthesis and activity of spirocyclic compounds as anti-tubercular agents. Both synthesized and naturally occurring spiro chemicals exhibit antitubercular properties. The promising antitubercular potential shown by some of the spirocyclic compounds has attracted scientists to explore them further to develop molecules with improved pharmacodynamic and pharmacokinetic properties and new mechanisms of action with enhanced safety and efficacy in tuberculosis. The current review covers the exploration of spiro compounds from the year 2004 to 2024 for the combat of Tuberculosis. This review gives the comprehensive advancements in this scaffold which would help the logical design of powerful, less toxic, and more effective spirocyclic anti-TB medicinal molecules.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-19"},"PeriodicalIF":3.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Designing molecular hybrids as novel breast cancer therapeutics.","authors":"Shagufta, Irshad Ahmad, Noora Ali Nasar, Sayma Zerin","doi":"10.1080/17568919.2025.2479418","DOIUrl":"10.1080/17568919.2025.2479418","url":null,"abstract":"","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-3"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}