Future medicinal chemistry最新文献

{"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}

{"title":"Synthesis, <i>in vitro</i> and <i>in-silico</i> evaluation of amide derivatives as prospective antimicrobial and antileishmanial agents.","authors":"Haroon Ur Rashid, Sher Wali Khan, Abdul Latif, Saira Nayab, Muhammad Naveed Umar, Fatima Sana, Abdul Bari Shah, Muhammad Zahoor, Riaz Ullah, Essam A Ali","doi":"10.1080/17568919.2025.2479419","DOIUrl":"https://doi.org/10.1080/17568919.2025.2479419","url":null,"abstract":"<p><p>This study focused on the synthesis, antimicrobial, and antileishmanial evaluation of seven amide derivatives (<b>AL-1</b> to <b>AL-7</b>). The target compounds were synthesized from <i>L-</i>cysteine methyl ester and various substituted aromatic and aliphatic carboxylic acids. The final products were characterized using physical and spectro-analytical techniques (FT-IR, ¹H NMR). The derivatives were evaluated for their antimicrobial activity at various concentrations. Experimental studies revealed that compounds <b>AL-5</b> and <b>AL-6</b> were the most potent against <i>Staphylococcus aureus</i> and <i>Escherichia coli</i>, exhibiting 18 mm and 21 mm inhibition zones, respectively, at a concentration of 2000 µg/mL. Additionally, <b>AL-5</b> and <b>AL-6</b> showed significant activity against <i>Candida albicans</i>, with 20 mm and 23 mm inhibition zones, respectively, at a concentration of 1000 µg/mL. The compounds also exhibited moderate to good activity against <i>Leishmania tropica</i>. Compounds <b>AL-2, AL-4, AL-5</b>, and <b>AL-6</b> demonstrated good activity, with IC₅₀ values of 0.68 ± 0.09, 0.68 ± 0.16, 0.66 ± 0.08, and 0.68 ± 0.12 µg/mL, respectively. Molecular docking, <i>in silico</i> Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis, and Density Functional Theory (DFT) studies were conducted on the most potent compounds (<b>AL-5</b> and <b>AL-6</b>) to validate and support their experimental antimicrobial and antileishmanial potential.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-14"},"PeriodicalIF":3.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647961","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":"Anti-breast cancer potential of thieno-pyrimidine derivatives as VEGFR-2 inhibitors.","authors":"Aisha A Alsfouk, Maged Mohammed Saleh Al Ward, Mustafa A Al-Qadhi, Souad A El-Metwally, Reda G Yousef, Eslam B Elkaeed, Dalal Z Husein, Fatma G Amin, Hazem Elkady, Ahmed M Metwaly, Ibrahim H Eissa","doi":"10.1080/17568919.2025.2479422","DOIUrl":"https://doi.org/10.1080/17568919.2025.2479422","url":null,"abstract":"<p><strong>Background: </strong>Thieno-pyrimidine derivatives have emerged as promising candidates for VEGFR-2 inhibition. This study aimed to design, synthesize, and evaluate novel thieno-pyrimidine derivatives for their anti-cancer potential.</p><p><strong>Methods: </strong>A series of thieno-pyrimidine compounds were synthesized and screened for <i>in vitro</i> cytotoxicity against MDA-231 and MCF-7 cell lines. The most active compound, <b>6b</b>, was further analyzed for VEGFR-2 kinase inhibition, wound healing, apoptosis induction, and cell cycle arrest. Molecular docking, 200 ns molecular dynamics simulations, MM-GBSA, ProLIF PCAT, and FEL analyses were conducted to assess binding stability. DFT calculations evaluated electronic properties, while <i>in silico</i> ADMET profiling predicted pharmacokinetics and toxicity.</p><p><strong>Results: </strong>Compound <b>6b</b> exhibited potent cytotoxicity with IC₅₀ values of 5.91 µM (MDA-231) and 7.16 µM (MCF-7). It demonstrated VEGFR-2 inhibition is comparable to sorafenib (IC₅₀: 53.63 ± 3.14 nM). Wound healing assays showed significant inhibition of MDA-231 migration. Flow cytometry confirmed apoptosis induction (57.20% early apoptosis) and G1 phase arrest. Gene expression analysis revealed upregulation of pro-apoptotic markers and downregulation of Bcl-2. Computational studies confirmed stable VEGFR-2 binding, and ADMET predictions indicated a favorable safety profile.</p><p><strong>Conclusion: </strong>Compound <b>6b</b> exhibits strong VEGFR-2 inhibition, potent anti-cancer effects, and a favorable toxicity profile, highlighting its potential for further therapeutic development.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-16"},"PeriodicalIF":3.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648006","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":"Leading prodrug strategies for targeted and specific release.","authors":"Rupa Bargakshatriya, Sumit Kumar Pramanik","doi":"10.1080/17568919.2025.2479412","DOIUrl":"https://doi.org/10.1080/17568919.2025.2479412","url":null,"abstract":"","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-4"},"PeriodicalIF":3.2,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630317","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":"Leading designs of peptide-based chemical probes for medical imaging- the dawn of precision diagnostics.","authors":"Giuseppe Floresta","doi":"10.1080/17568919.2025.2479415","DOIUrl":"10.1080/17568919.2025.2479415","url":null,"abstract":"","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-3"},"PeriodicalIF":3.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604490","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":"Design and application of CCR8 antagonists.","authors":"Tom Van Loy, Dominique Schols, Steven De Jonghe","doi":"10.1080/17568919.2025.2476381","DOIUrl":"https://doi.org/10.1080/17568919.2025.2476381","url":null,"abstract":"","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-3"},"PeriodicalIF":3.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596586","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":"Key developments in fluorinated heterocycles.","authors":"Carla Rizzo, Antonio Palumbo Piccionello","doi":"10.1080/17568919.2025.2476385","DOIUrl":"https://doi.org/10.1080/17568919.2025.2476385","url":null,"abstract":"","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-2"},"PeriodicalIF":3.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566687","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":"Synthesis and in vitro antitrypanosomatid activity of novel 5-nitroindole-rhodanine conjugates.","authors":"Emce Badenhorst, Janine Aucamp, Christina Kannigadu, Helena D Janse van Rensburg, Keisuke Suganuma, David D N'Da","doi":"10.1080/17568919.2025.2470110","DOIUrl":"10.1080/17568919.2025.2470110","url":null,"abstract":"<p><strong>Aim: </strong>Trypanosomatid diseases, leishmaniasis and trypanosomiasis are vector-borne parasitic diseases that can cause death and catastrophic economic losses for millions of people. The growing resistance of trypanosomatid parasites to current treatments highlights the urgent need for new therapeutic agents. This study explored 5-nitroindole-rhodanine conjugates to identify promising new compounds with the potential for future development as antitrypanosomatid treatments.</p><p><strong>Materials and methods: </strong>The conjugates were synthesized in a multi-step process and evaluated <i>in</i> <i>vitro</i> for antileishmanial activity against Leishmania (<i>L.</i>) <i>donovani</i> and <i>L.</i> <i>major</i> strains. Cytotoxicity was assessed on Vero and THP-1 cells. Due to the taxonomic relation to Trypanosoma spp. the compounds were also screened for in vitro activity against species that cause zoonotic trypanosomiasis.</p><p><strong>Results and conclusion: </strong>Several hits were found with leishmanicidal activity against both <i>L.</i> <i>donovani</i> and <i>L.</i> <i>major</i> strains. Of these, <b>3d</b> was identified as a potential early lead that exhibited nanomolar cidal activity against <i>L.</i> <i>major</i>, and greater selectivity than the reference drug amphotericin B. However, the compounds did not have similar activity levels against <i>Trypanosoma spp</i>. Hence, these compounds should be further investigated for their mechanism of action and <i>in</i> <i>vivo</i> antileishmanial activity to determine their potential as a leishmaniasis treatment.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"557-573"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491486","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}