Future medicinal chemistry最新文献_第8页

Isatin as a privileged scaffold for kinase inhibition: recent advances in anti-cancer research. Isatin作为激酶抑制的特殊支架：抗癌研究的最新进展。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-07-27 DOI: 10.1080/17568919.2026.2706110

Alia Mushtaq, Azmat Ullah Khan, Akasha Maqbool, Muhammad Shahzad, Muhammad Moazzam Naseer

{"title":"Isatin as a privileged scaffold for kinase inhibition: recent advances in anti-cancer research.","authors":"Alia Mushtaq, Azmat Ullah Khan, Akasha Maqbool, Muhammad Shahzad, Muhammad Moazzam Naseer","doi":"10.1080/17568919.2026.2706110","DOIUrl":"https://doi.org/10.1080/17568919.2026.2706110","url":null,"abstract":"Protein kinases are key therapeutic targets in anticancer drug discovery due to their central roles in regulating cell proliferation, survival, and signaling pathways. Among diverse heterocyclic scaffolds, isatin (indole-2,3-dione) has emerged as a privileged framework for the development of potent kinase inhibitors due to its structural versatility and favorable interaction profile within binding pockets. This review provides a comprehensive overview of recent advances in isatin-based kinase inhibitors, highlighting their design strategies, structure-activity relationships (SAR), and key molecular determinants of potency and selectivity. Particular emphasis is placed on structural optimization at the N-1 and C-5/C-7 positions, as well as hybridization with heterocyclic pharmacophores has yielded compounds with nanomolar inhibitory activity against clinically relevant targets, including cyclin dependent kinases (CDKs), vascular-endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR) and other kinases. In addition, ligand-kinase interactions are critically analyzed, with focus on hinge-region hydrogen bonding and hydrophobic complementarity within the ATP-binding site. Computational approaches, including molecular docking studies, are integrated to rationalize binding modes and support SAR interpretations. Collectively, this review underscores isatin as a versatile and promising scaffold for the rational design of next generation multitarget kinase inhibitors with potential applications in anticancer therapy.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-16"},"PeriodicalIF":3.3,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591236","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}

引用次数: 0

A comprehensive exploration of the structure-activity relationships, multitarget strategies, and therapeutic mechanisms of triazole scaffolds in Alzheimer's disease. 全面探讨三唑支架治疗阿尔茨海默病的构效关系、多靶点策略和治疗机制。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-07-01 Epub Date: 2026-06-09 DOI: 10.1080/17568919.2026.2684615

Aafreen Malvankar, Mahesh Raut, Sushil Kumar Singh, Rohit Singh, Neeraj Mahindroo, Nilesh Bajad

{"title":"A comprehensive exploration of the structure-activity relationships, multitarget strategies, and therapeutic mechanisms of triazole scaffolds in Alzheimer's disease.","authors":"Aafreen Malvankar, Mahesh Raut, Sushil Kumar Singh, Rohit Singh, Neeraj Mahindroo, Nilesh Bajad","doi":"10.1080/17568919.2026.2684615","DOIUrl":"10.1080/17568919.2026.2684615","url":null,"abstract":"The deposition of the Aβ peptide extracellularly as diffused and neuritic plaques and intracellular hyperphosphorylated tau (p-tau) protein as neurofibrillary tangles (NFTs) are the key pathological changes observed in the progression of AD. Despite advances in the neuroscience research, the discovery and development of effective therapeutic agents have become challenging task for AD. The molecules modulating multiple targets involved in the disease attracted much attention as promising tools for the effective therapeutic efficacy. Triazole scaffold has been consistently rewarded as a promising versatile lead molecule with a pivotal position in modern medicinal chemistry. It has shown potent inhibitory activity against different targets involved in the progression of the AD including activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), amyloid beta (Aβ) accumulation, tau aggregation, neuroinflammation and oxidative stress. Recent reviews label 1,2,3-triazole as first choice scaffold for designing multifunctional hybrid molecules for AD. A comprehensive literature search was performed using PubMed, Scopus, Web of Science, and Google Scholar databases covering publications from 2000 to 2026. This review critically analyzes the evolution of triazole-based therapeutics from single-target cholinesterase inhibitors to modern multitarget-directed ligands. We systematically evaluate how the structural versatility of the 1,2,3- and 1,2,4-triazole cores facilitates interactions with key AD pathological hallmarks.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1925-1941"},"PeriodicalIF":3.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204179","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 isoxazole-(thio-) and semicarbazone hybrids as promising antibacterial and anticancer agents: synthesis, characterization, biological evaluation, and in silico validation. 新型异恶唑-（硫代）和氨基脲杂合物作为有前景的抗菌和抗癌剂：合成、表征、生物学评价和硅验证。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-07-01 Epub Date: 2026-06-12 DOI: 10.1080/17568919.2026.2684542

Muneera S M Al-Saleem, Jehan Y Al-Humaidi, Abd Elaziz Rahhou, Yousef E Mukhrish, Bharath Kumar Chagaleti, M Y Ait Itto, Ali Oubella, Reda A Haggam

{"title":"Novel isoxazole-(thio-) and semicarbazone hybrids as promising antibacterial and anticancer agents: synthesis, characterization, biological evaluation, and in silico validation.","authors":"Muneera S M Al-Saleem, Jehan Y Al-Humaidi, Abd Elaziz Rahhou, Yousef E Mukhrish, Bharath Kumar Chagaleti, M Y Ait Itto, Ali Oubella, Reda A Haggam","doi":"10.1080/17568919.2026.2684542","DOIUrl":"10.1080/17568919.2026.2684542","url":null,"abstract":"Aims: This study aims to design and synthesize a new series of hybrid heterocyclic systems and to evaluate their anticancer and antimicrobial properties. Additionally, in silico analyses were performed to assess their molecular interactions, pharmacokinetic profiles, and potential as drug candidates.Materials & methods: The compounds were synthesized via a [3 + 2] cycloaddition reaction. Biological evaluations included in vitro cytotoxicity assays against four human cancer cell lines. Antibacterial activity was assessed against representative Gram-positive and Gram-negative strains. In silico studies encompassed molecular docking with bacterial protein targets, molecular dynamics simulations, and ADMET profiling.Results: The synthesized compounds (5-6) were successfully characterized and demonstrated moderate antiproliferative activity against cancer cell lines. Compound 6 showed slightly higher cytotoxicity than compound 5, with an IC50 of 17.16 ± 2.43 µM against A549. Both compounds exhibited notable antibacterial activity, particularly against Gram-negative strains. Docking studies revealed favorable binding energies at the active sites of selected bacterial proteins, while MD simulations confirmed the stability of ligand-protein complexes.Conclusions: This work demonstrates the successful synthesis and biological evaluation of novel isoxazole-based heterocyclic hybrids. Compound 6 emerged as the most promising candidate, exhibiting moderate anticancer activity, significant antibacterial effects, and strong in silico evidence of stable TLR4 inhibition.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1797-1816"},"PeriodicalIF":3.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148224481","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 and synthesis of pyrazole-heteroaryl arylhydrazone schiff base hybrids with antimicrobial and docking evaluation. 吡唑-杂芳基芳腙希夫碱杂合物的设计合成及其抗菌性及对接评价。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-07-01 Epub Date: 2026-06-08 DOI: 10.1080/17568919.2026.2678789

Asmaa L Alanzy, Mohamed N El-Bayaa, Dania Alweet, Ehab M Zayed, Wael A El-Sayed

{"title":"Design and synthesis of pyrazole-heteroaryl arylhydrazone schiff base hybrids with antimicrobial and docking evaluation.","authors":"Asmaa L Alanzy, Mohamed N El-Bayaa, Dania Alweet, Ehab M Zayed, Wael A El-Sayed","doi":"10.1080/17568919.2026.2678789","DOIUrl":"10.1080/17568919.2026.2678789","url":null,"abstract":"Background: The alarming rise of multidrug-resistant microbial infections underscores the urgent need for novel antimicrobial agents.Aim: A series of new pyrazole-based derivatives incorporating naphthalene and hydrazone pharmacophores were designed, synthesized, and studied for their antimicrobial activity with computational investigations.Materials and methods: Two pyrazole-naphthalene-hydrazone hybrid types were synthesized and structurally characterized. The antimicrobial activity was systematically evaluated against Escherichia coli, Helicobacter pylori, Bacillus cereus, Staphylococcus aureus, and Candida albicans using the well diffusion method while investigating minimum inhibitory concentration (MIC). Molecular docking was also conducted to investigate the binding affinity of potent products against microbial targets (PDB IDs 3t88, 3ty7, and 5k04). Density function theory (DTF) investigation was also performed.Results and conclusion: Compounds 3g and 4d demonstrated broad-spectrum antimicrobial activity with MIC values superior or comparable to the reference drug gentamicin. The results confirm that structural modifications at key positions on the pyrazole system, particularly with electron-withdrawing and bulky aromatic substituents, significantly enhanced activity. Molecular docking revealed enhanced binding interactions for possible inhibitory effects. DFT calculations showed insights into the electronic structure, molecular orbitals, and electrostatic potential of compound 3g. The results revealed the pyrazole-naphthalene hybrids as promising candidates for the development of new antimicrobial agents.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1649-1660"},"PeriodicalIF":3.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148198238","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 and synthesis of new curcumin analogues as hepatoprotectives and antioxidants in liver dysfunction through caspase-3 regulation. 新型姜黄素类似物的设计与合成：通过caspase-3调控作为肝脏保护和抗氧化剂的肝脏功能障碍。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-07-01 Epub Date: 2026-06-03 DOI: 10.1080/17568919.2026.2676783

Nashwa Hafez Zaher, Mohamed Ismail Mostafa, Marwa Galal El-Gazzar

{"title":"Design and synthesis of new curcumin analogues as hepatoprotectives and antioxidants in liver dysfunction through caspase-3 regulation.","authors":"Nashwa Hafez Zaher, Mohamed Ismail Mostafa, Marwa Galal El-Gazzar","doi":"10.1080/17568919.2026.2676783","DOIUrl":"10.1080/17568919.2026.2676783","url":null,"abstract":"Background: Chronic liver disease is a progressive, worldwide health crisis, with its incidence and prevalence increasing annually. It causes progressive liver injury and ultimately fibrosis. Globally, it is responsible for approximately 2 million deaths annually. Despite its growing prevalence, there is currently no approved, highly effective targeted therapy for managing liver dysfunction.Objective: Targeting caspase-3 activity may attenuate hepatocellular injury, reduce inflammation and oxidative stress, and thereby improve liver functional integrity.Methodology: Ten cyclic curcumin analogues (2-11) were synthesized, followed by preliminary screening for caspase-3 inhibitory activity. Their structures were confirmed by spectral and microanalytical data. The most active triazole (4) and sulfonamide (5) analogues were further evaluated in vivo to assess their anti-inflammatory, antioxidant, and caspase-3 inhibitory effects in rat liver tissue. Molecular docking study was performed to confirm caspase -3 regulation. Radiation stability study was held. Results: Analogues 4 and 5 significantly improved biochemical and molecular markers associated with liver dysfunction, including reductions in inflammation, oxidative stress, caspase-3 activity, TNF-α, p53, and Bax levels, alongside modulation of Bcl-2 expression.Conclusion: The triazole analogue 4 and sulfonamide analogue 5 demonstrate promising hepatoprotective activity and may represent stable lead compounds for potential therapeutic management of liver dysfunction.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1661-1677"},"PeriodicalIF":3.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13568570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148149283","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

Advances in the clinical potential of pyrimidine analogues as tubulin inhibitors in oncology. 嘧啶类似物作为肿瘤微管蛋白抑制剂的临床潜力研究进展。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-07-01 Epub Date: 2026-05-21 DOI: 10.1080/17568919.2026.2676780

Menglin Luo, Shuwang Jiang, Yufeng Ma, Peiliang Zhao

引用次数: 0

Novel nicotinic hydrazone derivatives as multitarget carbonic anhydrase and acetylcholinesterase inhibitors with anticancer potential: synthesis, biological evaluation and molecular docking studies. 具有抗癌潜力的新型烟碱腙衍生物多靶点碳酸酐酶和乙酰胆碱酯酶抑制剂：合成、生物学评价和分子对接研究。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-07-01 Epub Date: 2026-06-08 DOI: 10.1080/17568919.2026.2684670

Osman Nuri Aslan, Işıl Nihan Korkmaz, Fatma Necmiye Kacı, Pınar Kalın, Erbay Kalay, Uğur Güller, Ramazan Kalın

{"title":"Novel nicotinic hydrazone derivatives as multitarget carbonic anhydrase and acetylcholinesterase inhibitors with anticancer potential: synthesis, biological evaluation and molecular docking studies.","authors":"Osman Nuri Aslan, Işıl Nihan Korkmaz, Fatma Necmiye Kacı, Pınar Kalın, Erbay Kalay, Uğur Güller, Ramazan Kalın","doi":"10.1080/17568919.2026.2684670","DOIUrl":"10.1080/17568919.2026.2684670","url":null,"abstract":"Aims: This study aims to design and synthesize novel nicotinic hydrazone derivatives and evaluate their multitarget biological activities, including enzyme inhibition and anticancer potential.Materials and methods: The target compounds were synthesized via condensation of nicotinic hydrazide with various aldehydes, including Mannich base and acyl-substituted derivatives. Structural characterization was performed using 1H NMR, 13C NMR, FT-IR, and HRMS, and purity was confirmed by HPLC. Enzyme inhibition (hCA I, hCA II, and eeAChE), molecular docking, in silico ADME analysis, and cytotoxic activity against A549, HeLa, HepG2, and SH-SY5Y cell lines were evaluated.Results: Several compounds exhibited potent enzyme inhibition in the nanomolar range. Compounds 2c, 2a, and 2b showed the strongest inhibition against hCA I, hCA II, and eeAChE, respectively (Ki = 9.05-16.93 nM). Docking studies revealed favorable binding interactions, with compound 2f showing the highest overall affinity. All compounds complied with Lipinski's rule of five. Cytotoxicity studies demonstrated strong activity, particularly for compounds 2a, 2d, and 2e.Conclusions: Nicotinic hydrazone derivatives represent promising multitarget scaffolds with significant enzyme inhibitory and anticancer potential, warranting further investigation.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1835-1852"},"PeriodicalIF":3.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204228","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

Synthesis, characterization, in-silico, and in-vitro evaluation of 4-amino-N-(4-aminophenyl)benzene sulfonamide derivatives against Naja oxiana 5'-nucleotidases (5'-NT) enzyme. 4-氨基-n -（4-氨基苯基）苯磺酰胺衍生物的合成、表征、硅基和体外抗氧化Naja 5'-核苷酸酶（5'- nt）酶的评价

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-07-01 Epub Date: 2026-05-26 DOI: 10.1080/17568919.2026.2678999

Amina Noor Ul Huda, Bibi Fatima Nayyab, Muhammad Hassham Hassan Bin Asad, Nighat Fatima, Mehwish Jamil Noor, Sofia Khalid, Syed Sajid Hussain Shah, Abdul Mannan, Farhan A Khan, Muhammad Muzzmil, Sohail Anjum Shahzad

{"title":"Synthesis, characterization, in-silico, and in-vitro evaluation of 4-amino-N-(4-aminophenyl)benzene sulfonamide derivatives against Naja oxiana 5'-nucleotidases (5'-NT) enzyme.","authors":"Amina Noor Ul Huda, Bibi Fatima Nayyab, Muhammad Hassham Hassan Bin Asad, Nighat Fatima, Mehwish Jamil Noor, Sofia Khalid, Syed Sajid Hussain Shah, Abdul Mannan, Farhan A Khan, Muhammad Muzzmil, Sohail Anjum Shahzad","doi":"10.1080/17568919.2026.2678999","DOIUrl":"10.1080/17568919.2026.2678999","url":null,"abstract":"Aim: 5'-Nucleotidase (5'-NT) enzyme has been reported for its detrimental effects post-Naja oxiana (N. oxiana) envenomation via generation of adenosine moiety. Therefore, the present study was designed to evaluate anti-5'-NT potentials of various 4-amino-N-(4-aminophenyl)benzene sulfonamide derivatives (HAS-series).Methods: Targeted compounds were studied computationally and subsequently synthesized and analyzed with different spectroscopic techniques. Furthermore, these analogues were evaluated in vitro for their potentials to halt 5'-NT activity.Results: Among the 10 newly synthesized compounds, HAS-1 (IC50 = 12 ng/mL, 99% effective) and HAS-2 (IC50 = 18 ng/mL, 96% effective) showed remarkable potentials (p > 0.5) when compared with standard antidote having low binding energies (-8.1 kcal/mol and -7.5 kcal/mol) against the target. Favorable pharmacokinetic safety profile was observed characterized with high absorption, compliance in Lipinski's rule, low penetration power to the brain with effective bioavailability.Conclusions: Based on the data compiled, both potential analogues could be promising target against 5'-NT to cope with adenosine-induced toxicities. However, detailed study is inevitable to access their lipophilicity and toxicity profile prior safely use in the victims.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1679-1686"},"PeriodicalIF":3.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148028910","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 coumarin-1,2,3-triazole-isatin hybrids: design, synthesis, in-vitro, in-silico and SAR study for antimicrobial activity and α-glucosidase inhibition. 新型香豆素-1,2,3-三唑-isatin杂合物的设计、合成、体外、硅和SAR研究及其抑菌活性和α-葡萄糖苷酶抑制作用。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-07-01 Epub Date: 2026-05-29 DOI: 10.1080/17568919.2026.2676786

Mansi, Shilpa Yadav, Priyanshu, Pratibha Chanana, Pankaj Khanna, Charu Bhutani, Leena Khanna

{"title":"Novel coumarin-1,2,3-triazole-isatin hybrids: design, synthesis, in-vitro, in-silico and SAR study for antimicrobial activity and α-glucosidase inhibition.","authors":"Mansi, Shilpa Yadav, Priyanshu, Pratibha Chanana, Pankaj Khanna, Charu Bhutani, Leena Khanna","doi":"10.1080/17568919.2026.2676786","DOIUrl":"10.1080/17568919.2026.2676786","url":null,"abstract":"Aim: The present study aims to design and synthesise novel Coumarin-1,2,3-Triazole-Isatin hybrids (9a-l) and evaluate their dual biological potential as antimicrobials and α-Glucosidase Inhibitors.Materials and methods: The series was synthesized using CuAAC Click chemistry and characterized using NMR and HRMS techniques. In vitro antimicrobial and antidiabetic potentials were evaluated against B. subtilis, L. rhamnosus, E. coli, and C. albicans, and α-glucosidase enzyme, respectively. Additionally, in silico studies against DNA gyrase of E. coli (PDB ID: 1KZN), C. albicans (PDB ID: 1IYL), and (PDB ID: 3AJ7) were performed using molecular docking, MD simulation, and DFT methods.Results and discussion: The synthesized hybrids have shown significant antimicrobial activity; 9a was found best against B. subtilis (MIC = 2.32 μM). SAR analysis indicated the influence of chain length and substituent type on antimicrobial activity; however, n = 4 and X = Br was found most effective against each microbial strain. The antimicrobial action of 9b and 9h against B.subtilis was validated via SEM, showing bacterial cell wall disruption. 9j showed strongest antidiabetic potential (IC50 = 515.40 µM), comparable to acarbose (IC50= 425.94µM). Lastly, 100 ns MD simulations validated both in silico and in vitro findings by confirming the stability of protein-ligand complexes.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1713-1729"},"PeriodicalIF":3.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053735","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 in vitro evaluation of novel longifolene derivatives for Alzheimer's disease. 阿尔茨海默病新型长叶烯衍生物的设计、合成和体外评价。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-07-01 Epub Date: 2026-05-26 DOI: 10.1080/17568919.2026.2676784

Ami Thakkar, RajaSekhar Reddy Alavala, Ginpreet Kaur, Amruta Gadade, Vikas Dighe, Amisha Vora

{"title":"Design, synthesis, and in vitro evaluation of novel longifolene derivatives for Alzheimer's disease.","authors":"Ami Thakkar, RajaSekhar Reddy Alavala, Ginpreet Kaur, Amruta Gadade, Vikas Dighe, Amisha Vora","doi":"10.1080/17568919.2026.2676784","DOIUrl":"10.1080/17568919.2026.2676784","url":null,"abstract":"Aim: The study combines computational and experimental approaches to provide structural and functional features of novel ligands, emphasizing their promising role as canditates for Alzheimer's disease (AD) drug development.Materials and methods: The research focused on developing molecules capable of targeting acetylcholinesterase (AChE) enzyme as potential treatments for AD. Starting with longifolene, a natural compound known for its anti-inflammatory properties, 198 derivatives were designed. Structure-guided molecular docking, MD simulations, and MM/GBSA free energy calculations identified four compounds that exhibited favorable interactions on AChE. These compounds were synthesized and characterized, followed by series of biological evaluation. Donepezil hydrochloride was used as the standard reference drug.Results: Cytotoxicity assay conducted established its safety on SH-SY5Y cells with IC50 exceeding 90 µM. In the in vitro model developed for AD using Aβ1-42, the ligands demonstrated anti-inflammatory and neuroprotective effects with compound 4f showing promising effect. At 0.1 and 0.3 µM, compound 4f significantly decreased intracellular reactive oxygen species, preserved mitochondrial membrane potential, and reduced cellular apoptosis.Conclusions: The results identify compound 4f as a promising lead candidate for AD management. The molecular hybridization strategy successfully enhances biological activity, supporting further preclinical development of longifolene-derived scaffolds as potential anti-Alzheimer's therapeutics.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1687-1699"},"PeriodicalIF":3.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148028956","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