Future medicinal chemistry最新文献

Unveiling the potential of HS-1793: a review of its anticancer properties and therapeutic promise. 揭示 HS-1793 的潜力：综述其抗癌特性和治疗前景。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-11-18 DOI: 10.1080/17568919.2024.2424150

Xavier Capó, Manuel Jiménez-Garcia, Farukh Sharopov, Patrick Valere Tsouh Fokou, Miquel Martorell, Afaf Ahmed Aldahish, Raffaele Pezzani, Javad Sharifi-Rad, Daniela Calina

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 : 2024-11-14 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

In vivo evaluation of novel synthetic pyrazolones as CDK9 inhibitors with enhanced pharmacokinetic properties. 作为 CDK9 抑制剂的新型合成吡唑酮的体内评价，其药代动力学特性得到增强。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-11-12 DOI: 10.1080/17568919.2024.2419363

Ebtehal M Husseiny, Hamada S Abulkhair, Samiha A El-Sebaey, Manal M Sayed, Kurls E Anwer

引用次数: 0

New immunomodulatory anticancer quinazolinone-based thalidomide analogs: design, synthesis and biological evaluation. 基于喹唑啉酮的新型免疫调节抗癌沙利度胺类似物：设计、合成和生物学评价。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-11-12 DOI: 10.1080/17568919.2024.2419361

Maged Mohammed Saleh Al Ward, Abdallah E Abdallah, Mohamed F Zayed, Rezk R Ayyad, Tamer M Abdelghany, Dina Abed Bakhotmah, Mohamed Ayman El-Zahabi

{"title":"New immunomodulatory anticancer quinazolinone-based thalidomide analogs: design, synthesis and biological evaluation.","authors":"Maged Mohammed Saleh Al Ward, Abdallah E Abdallah, Mohamed F Zayed, Rezk R Ayyad, Tamer M Abdelghany, Dina Abed Bakhotmah, Mohamed Ayman El-Zahabi","doi":"10.1080/17568919.2024.2419361","DOIUrl":"https://doi.org/10.1080/17568919.2024.2419361","url":null,"abstract":"Aim: The current work is an extension to our previous work for the development of new thalidomide analogs.Materials & methods: Quinazolinone-based molecules carrying a glutarimide moiety have been designed, synthesized and biologically evaluated for immunomodulatory and anticancer activity.Results: Compounds 7d and 12 showed considerable immunomodulatory properties in comparison to thalidomide. 7d and 12 significantly reduced TNF-α levels in HepG-2 cells from 162.5 to 57.4 pg/ml and 49.2 pg/ml, respectively, compared with 53.1 pg/ml reported for thalidomide. Moreover, they caused 69.33 and 77.74% reduction in NF-κB P65, respectively, compared with 60.26% reduction for thalidomide. Similarly, they reduced VEGF from 432.5 to 161.3 pg/ml and 132.8 pg/ml, respectively, in comparison to 153.2 pg/ml reported for thalidomide. The two new derivatives, 7d and 12 also showed about eightfold increases in caspase-8 levels in cells treated with them. These results were slightly better than those of thalidomide. The obtained results revealed that Compound 12 had better immunomodulatory properties than thalidomide, with stronger effects on TNF-α, NF-κB P65, VEGF and caspase-8.Conclusion: This work indicates that compounds 7d and 12 have interesting biological properties that should be further evaluated and modified in order to develop clinically useful thalidomide analogs.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618081","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 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":null,"pages":null},"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

Cu(II) complexes based on benzimidazole ligands: synthesis, characterization, DFT, molecular docking & bioactivity study. 基于苯并咪唑配体的 Cu(II) 复合物：合成、表征、DFT、分子对接和生物活性研究。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-11-12 DOI: 10.1080/17568919.2024.2419353

Muhamad Azwan Hamali, Miah Roney, Amit Dubey, Md Nazim Uddin, Nur Amira Zulkifli, Mohd Fadhlizil Fasihi Mohd Aluwi, Maslinda Musa, Amalina Mohd Tajuddin, Karimah Kassim

{"title":"Cu(II) complexes based on benzimidazole ligands: synthesis, characterization, DFT, molecular docking & bioactivity study.","authors":"Muhamad Azwan Hamali, Miah Roney, Amit Dubey, Md Nazim Uddin, Nur Amira Zulkifli, Mohd Fadhlizil Fasihi Mohd Aluwi, Maslinda Musa, Amalina Mohd Tajuddin, Karimah Kassim","doi":"10.1080/17568919.2024.2419353","DOIUrl":"https://doi.org/10.1080/17568919.2024.2419353","url":null,"abstract":"Aim: The biggest cause of cancer deaths globally was lung cancer. New cancer fighting drugs are needed due to the rising number of cancer patients and cancer cells' treatment resistance.Results: Two Cu(II) complexes, synthesized from ligands based on 2-aminomethyl benzimidazole and salicylaldehyde derivatives, were designed and evaluated for their effectiveness against A549 lung cancer. The compounds were subjected to computational calculation using Density Functional Theory (DFT) to gather information on their reactivity. Furthermore, molecular docking are utilized to simulate the interaction between the compound and the MPP-9 protein. The synthesis of the ligands and their Cu(II) metal complexes are efficient and straightforward. The complexation between copper atom and the ligand are in 1:1 ratio. The MTT assay of the compounds against A549 lung carcinoma reveals that the both Cu(II) complexes good cytotoxicity activity, in comparison to their respective ligands. The low HOMO-LUMO band gap based on the DFT calculation predicts the high reactivity of the compounds. Furthermore, the low binding energy and the numbers of interactions of the Cu(II) complexes with MMP-9 protein binding site coincide with the antiproliferative activity tested in vitro.Conclusion: The cytotoxicity studies performed for Cu(L1Br) are promising, indicating a good candidate for a future drug.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618062","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":null,"pages":null},"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