Future medicinal chemistry最新文献_第9页

New 4-amino-3-chloro benzoate ester derivatives as EGFR inhibitors: synthesis, in silico and biological analyses. 作为表皮生长因子受体抑制剂的新型 4-氨基-3-氯苯甲酸酯衍生物：合成、硅学和生物学分析。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-12-01 Epub Date: 2024-11-20 DOI: 10.1080/17568919.2024.2431478

Nedaa A Abd Al Rahim, Ammar A Razzak Mahmood, Lubna H Tahtamouni, Mai F AlSakhen, Salem R Yasin, Abdulrahman M Saleh

{"title":"New 4-amino-3-chloro benzoate ester derivatives as EGFR inhibitors: synthesis, in silico and biological analyses.","authors":"Nedaa A Abd Al Rahim, Ammar A Razzak Mahmood, Lubna H Tahtamouni, Mai F AlSakhen, Salem R Yasin, Abdulrahman M Saleh","doi":"10.1080/17568919.2024.2431478","DOIUrl":"10.1080/17568919.2024.2431478","url":null,"abstract":"Aim: The main goal of this study was to synthesize new derivatives of 4-amino-3-chloro benzoate ester, including 1,3,4-oxadiazole derivatives (N3a-d), benzohydrazone derivatives (N4a-c), and hydrazine-1-carbothioamide derivatives (N5a-d) that target epidermal growth factor receptor (EGFR) tyrosine kinase.Materials & methods: The new derivatives were characterized using various spectroscopic techniques. Docking studies were used to investigate the binding patterns to EGFR, and the anti-proliferative properties were tested in vitro.Results: In silico analysis showed that the hydrazine-1-carbothioamide derivatives (N5a-d) had the best matching pattern with EGFR pharmacophoric queries compared to erlotinib, exhibited a favorable safety profile, and showed the best stability among the tested compounds. Compound N5a induced cytotoxicity in the three cancer cell lines tested (A549, HepG2, and HCT-116), by targeting EGFR and activating caspase 3 and caspase 8, therefore, inducing the extrinsic apoptotic pathway.Conclusion: The results of this study show that compound N5a is a promising cytotoxic compound that inhibits the tyrosine kinase activity of EGFR.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2647-2662"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681440","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 of arylated tetrahydrobenzo[H]quinoline-3-carbonitrile derivatives as potential hits for treatment of diabetes. 合成芳基化四氢苯并[H]喹啉-3-甲腈衍生物，作为治疗糖尿病的潜在药物。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-12-01 Epub Date: 2024-11-12 DOI: 10.1080/17568919.2024.2419359

Faiza Seraj, Fouzia Naz, Musa Özil, Nimet Baltaş, Syeda Sumayya Tariq, Zaheer Ul-Haq, Uzma Salar, Muhammad Taha, Khalid Mohammed Khan

{"title":"Synthesis of arylated tetrahydrobenzo[H]quinoline-3-carbonitrile derivatives as potential hits for treatment of diabetes.","authors":"Faiza Seraj, Fouzia Naz, Musa Özil, Nimet Baltaş, Syeda Sumayya Tariq, Zaheer Ul-Haq, Uzma Salar, Muhammad Taha, Khalid Mohammed Khan","doi":"10.1080/17568919.2024.2419359","DOIUrl":"10.1080/17568919.2024.2419359","url":null,"abstract":"Aim: Quinoline scaffolds are serving as the core structure for numerous antifungal, analgesic, antipyretic, anti-inflammatory drugs as well as have also been investigated for their potential antidiabetic properties. Though further exploration is required in this area as the current antidiabetic agents, such as acarbose, miglitol and voglibose, are associated with several adverse side effects. In this context, arylated tetrahydrobenzo[H]quinoline-3-carbonitrile derivatives were designed and evaluated as potential antidiabetic agents.Materials & methods: A one-pot multicomponent reaction of 6-methoxy-1-tetralone with ethyl cyanoacetate, ammonium acetate and varying aldehydes yielded a range of new arylated tetrahydrobenzo[h]quinoline-3-carbonitrile molecules 1-36.Results: Compounds 2-5, 12, 13, 19 and 32-34 showed excellent inhibition against α-amylase (IC50 = 3.42-15.14 μM) and α-glucosidase (IC50 = 0.65-9.23 μM) enzymes in comparison to the standard acarbose (IC50 = 14.35 μM). In addition, all compounds revealed significant to moderate DPPH radical scavenging activity (SC50 = 21.30-138.30 μM) compared with BHT (SC50 = 64.40 μM). Kinetic studies confirmed competitive inhibition mode, while molecular docking studies comprehend ligands' interaction with enzyme's active sites and absorption, distribution, metabolism, and excretion analysis confirms that all synthetic derivatives are nontoxic.Conclusion: This research offers a range of lead candidates to become antidiabetic agents after further advanced study.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2609-2625"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618084","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

Autophagy degradation: a promising dimension in drug discovery for neurodegenerative diseases. 自噬降解：神经退行性疾病药物发现的一个前景广阔的领域。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-12-01 Epub Date: 2024-11-27 DOI: 10.1080/17568919.2024.2431477

Shuai-Jiang Liu, Chenxi Cai, Hong-Ping Zhu, Xiang Li, Bo Han

引用次数: 0

Organoselenium compounds beyond antioxidants. 除抗氧化剂外的有机硒化合物。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-12-01 Epub Date: 2024-12-22 DOI: 10.1080/17568919.2024.2435254

Ritu Mamgain, Garima Mishra, Saumya Kriti, Fateh V Singh

引用次数: 0

New pyrano-pyridine conjugates as potential anticancer agents: design, synthesis and computational studies. 作为潜在抗癌剂的新吡喃吡啶共轭物：设计、合成和计算研究。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-12-01 Epub Date: 2024-11-24 DOI: 10.1080/17568919.2024.2431475

Aladdin M Srour, Eman S Nossier, Najla A Altwaijry, Safeya M Mousa, Hanem M Awad, Heba S A Elzahabi

引用次数: 0

In-vitro and in-silico assessment of thiazole-thiazolidinone derivatives as selective inhibitors of urease and α-glucosidase. 噻唑-噻唑烷酮衍生物作为脲酶和α-葡萄糖苷酶选择性抑制剂的体外和计算机评价。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-12-01 Epub Date: 2024-12-08 DOI: 10.1080/17568919.2024.2432303

Yousaf Khan, Rafaqat Hussain, Wajid Rehman, Shoaib Khan, Aneela Maalik, Tayyiaba Iqbal, Tariq Aziz, Muhammad Irfan Afridi, Metab Alharbi, Abdullah F Alasmari

{"title":"In-vitro and in-silico assessment of thiazole-thiazolidinone derivatives as selective inhibitors of urease and α-glucosidase.","authors":"Yousaf Khan, Rafaqat Hussain, Wajid Rehman, Shoaib Khan, Aneela Maalik, Tayyiaba Iqbal, Tariq Aziz, Muhammad Irfan Afridi, Metab Alharbi, Abdullah F Alasmari","doi":"10.1080/17568919.2024.2432303","DOIUrl":"10.1080/17568919.2024.2432303","url":null,"abstract":"Aims: Current research work aims to synthesize hybrid compounds with a thiazole-thiazolidinone structure, as potent inhibitors of urease and α-glucosidase enzymes.Materials and methods: These compounds were characterize through1HNMR,13CNMR and HREI-MS techniques. These compounds were also evaluated for their potential to inhibit urease and α-glucosidase enzymes for the treatment of urinary tract infections (UTIs) and diabetes treatments. Moreover, molecular docking and ADMET analysis was carried out to confirm biological outcomes.Results and conclusion: Compounds-4 (IC50 = 1.80 ± 0.80 and 3.61 ± 0.59 μM against urease and α-glucosidase, respectively) exhibited significant effectiveness in inhibiting the activity of both enzymes in comparison to the conventional inhibitors thiourea and acarbose. Molecular docking experiments showed that potent compounds exhibited favorable binding orientations in the active sites of urease and α-glucosidase playing a pivotal role in inhibition profile of these compounds. These compounds were also investigated for their drug likeness and were found with desirable attributes for pharmaceutical development. Based on the findings of this research, these compounds have the potential to be developed into effective anti-diabetic and anti-urease treatments in the future.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2627-2636"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794578","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

Machine learning-based prediction of bioactivity in HIV-1 protease: insights from electron density analysis. 基于机器学习的 HIV-1 蛋白酶生物活性预测：电子密度分析的启示。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-12-01 Epub Date: 2024-11-12 DOI: 10.1080/17568919.2024.2419350

Vladislav Naumovich, Shivananda Kandagalla, Maria Grishina

{"title":"Machine learning-based prediction of bioactivity in HIV-1 protease: insights from electron density analysis.","authors":"Vladislav Naumovich, Shivananda Kandagalla, Maria Grishina","doi":"10.1080/17568919.2024.2419350","DOIUrl":"10.1080/17568919.2024.2419350","url":null,"abstract":"Aim: To develop a model for predicting the biological activity of compounds targeting the HIV-1 protease and to establish factors influencing enzyme inhibition.Materials & methods: Machine learning models were built based on a combination of Richard Bader's theory of Atoms in Molecules and topological analysis of electron density using experimental x-ray 'protein-ligand' complexes and inhibition constants data.Results & conclusion: Among all the models tested, logistic regression achieved the highest accuracy of 0.76 on the test set. The model's ability to differentiate between less active and highly active classes was relatively good, as indicated by an AUC-ROC score of 0.77. The analysis identified several critical factors affecting the biological activity of HIV-1 protease inhibitors, including the electron density contribution of hydrogen atoms, bond-critical points and particular amino acid residues. These findings provide new insights into how these molecular factors influence HIV-1 protease inhibition, emphasizing the importance of hydrogen bonding, glycine's flexibility and hydrophobic interactions in ligand binding.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2599-2607"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618077","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 nicotinamides as immunomodulatory VEGFR-2 inhibitors and apoptosis inducers. 作为免疫调节 VEGFR-2 抑制剂和细胞凋亡诱导剂的新型烟酰胺的设计与合成。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-12-01 Epub Date: 2024-11-14 DOI: 10.1080/17568919.2024.2421150

Reda G Yousef, Ibrahim H Eissa, Hazem Elkady, Ahmed B M Mehany, Mariam Ali Abo-Saif, Mohamed M Radwan, Mahmoud A ElSohly, Ibrahim M Ibrahim, Alaa Elwan, Mohamed Ayman El-Zahabi

引用次数: 0

Exploration of newly synthesized transition metal(II) complexes for infectious diseases. 探索新合成的过渡金属（II）配合物在传染性疾病中的应用。

IF 4.2 4区医学

Future medicinal chemistry Pub Date : 2024-09-19 DOI: 10.1080/17568919.2024.2389766

Binesh Kumar,Jai Devi,Amit Dubey,Manish Kumar

{"title":"Exploration of newly synthesized transition metal(II) complexes for infectious diseases.","authors":"Binesh Kumar,Jai Devi,Amit Dubey,Manish Kumar","doi":"10.1080/17568919.2024.2389766","DOIUrl":"https://doi.org/10.1080/17568919.2024.2389766","url":null,"abstract":"Aim: In the annals of human history, infectious diseases significantly influencing the collective well-being of people worldwide. Consequently, to identify effective agents for infectious ailments, the octahedral Co(II), Ni(II), Cu(II), Zn(II) complexes of 4-(3-methoxyphenyl)pyrimidin-2-amine and 2-methoxy-1-napthaldehyde based ligand were synthesized and well characterized in the current investigation.Results & methodology: The synthesized compounds were evaluated for anti-TB, anti-inflammatory, antibacterial, antifungal activities by microplate Alamar blue, bovine serum albumin, serial dilution assays. The [Zn(L1)2(H2O)2] complex (5) demonstrates robust potency with 0.0040 ± 0.0007 and 0.0038 μmol/ml MIC value in anti-tuberculosis and antimicrobial activities, correspondingly while 06.57 ± 0.03 μM IC50 value in anti-inflammatory investigation.Conclusion: Complex (5) show promising potential as targets for pathogen deformities, supported by rigorous biological and computational investigations including pharmacophore modelling, molecular docking (binding score -121.018 and -59.8662 kcal/mol for 6H53 and 1CX2 proteins, respectively), DFT (Density functional theory), MESP (Molecular Electrostatic Potential) and ADMET (absorption, distribution, metabolism, excretion and toxicity).","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":"215 1","pages":"1-19"},"PeriodicalIF":4.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259949","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

Semicarbazone, thiosemicarbazone tailed isoxazoline-pyrazole: synthesis, DFT, biological and computational assessment. 半咔唑酮、硫代咔唑酮尾部异噁唑啉-吡唑：合成、DFT、生物学和计算评估。

IF 4.2 4区医学

Future medicinal chemistry Pub Date : 2024-09-18 DOI: 10.1080/17568919.2024.2394011

Abdoullah Bimoussa,Mouhi Eddine Hachim,Khalil El Khatabi,Yassine Laamari,Ali Oubella,Mohamed F AlAjmi,Aziz Auhmani,Mohammed Aziz Ajana,Hamid Morjani,My Youssef Ait Itto

引用次数: 0