Future medicinal chemistry最新文献_第3页

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 : 2024-11-14 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

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 : 2024-11-12 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":"https://doi.org/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":"1-17"},"PeriodicalIF":3.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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 : 2024-11-12 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":"https://doi.org/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":"1-9"},"PeriodicalIF":3.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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

One-pot synthesis and pharmacological evaluation of new quinoline/pyrimido-diazepines as pulmonary antifibrotic agents. 作为肺部抗纤维化药物的新型喹啉/嘧啶二氮杂卓的单锅合成和药理学评价。

IF 4.2 4区医学

Future medicinal chemistry Pub Date : 2024-09-18 DOI: 10.1080/17568919.2024.2394018

Michael Atef Fawzy,Karim Hagag Ibrahim,Ashraf A Aly,Asmaa H Mohamed,Sara Mohamed Naguib Abdel Hafez,Walaa Yehia Abdelzaher,Eslam B Elkaeed,Aisha A Alsfouk,El-Shimaa Mn Abdelhafez

{"title":"One-pot synthesis and pharmacological evaluation of new quinoline/pyrimido-diazepines as pulmonary antifibrotic agents.","authors":"Michael Atef Fawzy,Karim Hagag Ibrahim,Ashraf A Aly,Asmaa H Mohamed,Sara Mohamed Naguib Abdel Hafez,Walaa Yehia Abdelzaher,Eslam B Elkaeed,Aisha A Alsfouk,El-Shimaa Mn Abdelhafez","doi":"10.1080/17568919.2024.2394018","DOIUrl":"https://doi.org/10.1080/17568919.2024.2394018","url":null,"abstract":"Aim: Pulmonary fibrosis is a life threating disease which requires an immediate treatment and due to the limited medications, this study focused on synthesizing a series of quinoline-based pyrimidodiazepines 4a-f as a novel antifibrotic hit.Materials & methods: The target compounds were synthesized via a one-pot reaction then investigated in a rat model of lung fibrosis induced by bleomycin (BLM).Results: Results revealed significant attenuation of the tested pro-inflammatory cytokines, fibrotic genes and apoptotic markers; however, Bcl-2 was upregulated, indicating a protective effect against fibrosis. Moreover, the molecular docking studies highlighted promising interactions between compounds 4b and 4c and specific amino acids within the protein pockets of caspase-3 (ARG341 and THR177), malondialdehyde (LYS195, LYS118 and ARG188) and TNF-α (SER99 and NME102).Conclusion: Compounds 4b and 4c emerge as promising candidates for further preclinical investigation as pulmonary antifibrotic agents.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":"48 1","pages":"1-20"},"PeriodicalIF":4.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259999","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

Synthesis, biological and computational evaluation of benzoxazole hybrid analogs as potential anti-Alzheimer's agents. 苯并恶唑杂化类似物的合成、生物学和计算评估，作为潜在的抗阿尔茨海默氏症药物。

IF 4.2 4区医学

Future medicinal chemistry Pub Date : 2024-09-13 DOI: 10.1080/17568919.2024.2393569

Mohamed S Othman,Rafaqat Hussain,Fazal Rahim,Hayat Ullah,Shoaib Khan,Muhammad Taha,Mohamed A Fareid,Anas T Altaleb,Shimaa M Aboelnaga,Syed Adnan Ali Shah

引用次数: 0

A novel class of potent antiangiogenic and antioxidant pyrazoles: synthesis, bioactivity, docking and ADMET studies. 一类新型强效抗血管生成和抗氧化吡唑：合成、生物活性、对接和 ADMET 研究。

IF 4.2 4区医学

Future medicinal chemistry Pub Date : 2024-09-12 DOI: 10.1080/17568919.2024.2394020

Siddaram Nadigar,Rohith Gattu,Sanjay Ramesh,Rekha N Dharmappa,Vijendra Kumar Nanjundaswamy,Suhas Ramesh

{"title":"A novel class of potent antiangiogenic and antioxidant pyrazoles: synthesis, bioactivity, docking and ADMET studies.","authors":"Siddaram Nadigar,Rohith Gattu,Sanjay Ramesh,Rekha N Dharmappa,Vijendra Kumar Nanjundaswamy,Suhas Ramesh","doi":"10.1080/17568919.2024.2394020","DOIUrl":"https://doi.org/10.1080/17568919.2024.2394020","url":null,"abstract":"Aim: Angiogenesis is the hallmark of cancer progression driven by VEGF/VEGFR-2 signalling pathway, inhibition of which could be a solution to tackle the progression of tumour cells and thus arresting their growth.Materials & methods: A novel class of pyrazoles was synthesized using arginine and dibromo ketones. Antiangiogenic activity was performed by in vivo yolk sac method. Antioxidant activity was evaluated by hydroxyl and superoxide radical scavenging assays. Docking studies were performed to determine the pyrazoles' binding potential with VEGFR-2 receptor and VEGF tyrosine kinase. ADMET properties were calculated using SwissADME and admetSAR for drug-likeness.Results: Compounds 5a-e showed significant antiangiogenic effects. Compound 5f exhibited effective hydroxyl and superoxide radical scavenging activities. Docking results confirmed the potential binding efficiency with VEGFR-2 receptor over VEGF tyrosine kinase, thus, functioning as competitive-inhibitors. ADMET studies revealed that the compounds possess favourable drug-like qualities.Conclusion: This study presents a novel class of pyrazoles as promising antioxidant and antiangiogenic agents with favourable drug-likeness properties.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":"88 1","pages":"1-16"},"PeriodicalIF":4.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142195506","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

Discovery of novel dihydro-pyrimidine hybrids: insight into the design, synthesis, biological evaluation and absorption, distribution, metabolism and excretion studies. 发现新型二氢嘧啶混合物：深入了解设计、合成、生物评估以及吸收、分布、代谢和排泄研究。

IF 4.2 4区医学

Future medicinal chemistry Pub Date : 2024-09-12 DOI: 10.1080/17568919.2024.2389767

Uzma Arshad,Nusrat Shafiq,Shagufta Parveen,Maryam Rashid

引用次数: 0

Synthesis, anticancer activity, docking and computational studies of new pyridyl-glycosyl hybrids and acyclic analogs. 新型吡啶基-糖基杂交化合物和无环类似物的合成、抗癌活性、对接和计算研究。

IF 4.2 4区医学

Future medicinal chemistry Pub Date : 2024-09-12 DOI: 10.1080/17568919.2024.2389768

Mohamed N El-Bayaa,Eman R Kotb,Sabri Messaoudi,Hanem M Awad,Mahmoud G Saleh,Hanan A Soliman

引用次数: 0