Future medicinal chemistry最新文献

The design and development of LRRK2 inhibitors as novel therapeutics for Parkinson's disease.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-12-24 DOI: 10.1080/17568919.2024.2444875

Xiaoxue Bai, Jiawei Zhu, Yao Chen, Haopeng Sun

引用次数: 0

Targeting undruggable protein KRAS for cancer therapy: novel opportunities and challenges.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-12-23 DOI: 10.1080/17568919.2024.2444865

Xin Yang, Xiang Li, Yue-Lin Zhang, Sheng-Nan Zhang, Miao Zhang, Chong Sun, Li Yang, Hong-Min Liu, Shuo Yuan

引用次数: 0

Organoselenium compounds beyond antioxidants.

IF 3.2 4区医学

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

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

引用次数: 0

Novel inhibitors of PARP1 and PARP14: design, synthesis, and potentiation of cisplatin efficacy in cancer.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-12-18 DOI: 10.1080/17568919.2024.2437972

Caleb M T Kam, Amanda L Tauber, Matthew S Zunk, Catherine M McDermott, Stephan M Levonis, Stephanie S Schweiker

{"title":"Novel inhibitors of PARP1 and PARP14: design, synthesis, and potentiation of cisplatin efficacy in cancer.","authors":"Caleb M T Kam, Amanda L Tauber, Matthew S Zunk, Catherine M McDermott, Stephan M Levonis, Stephanie S Schweiker","doi":"10.1080/17568919.2024.2437972","DOIUrl":"https://doi.org/10.1080/17568919.2024.2437972","url":null,"abstract":"Background: Poly(ADP-ribose) polymerase (PARP) is a superfamily of enzymes involved in cell survival. Both PARP1 and PARP14 are overexpressed in malignancies. No clinically approved PARP14 inhibitors are available, and PARP1 inhibitors are generally nonspecific, resulting in a need for a more diverse library of selective PARP1 and PARP14 inhibitors.Materials and methods: Based on the previous lead compounds 1 and 2, 26 novel compounds were designed, synthesized, and screened against PARP1 and PARP14. Compounds with the best in vitro inhibitory results were further screened against PARP2, PARP3, PARP5a, PARP7, and PARP15.Results and conclusion: The 26 novel compounds demonstrated a lesser inhibitory effect than the lead compounds. Compounds 1 and 2 were further investigated using in vitro cell viability assays, which revealed that cells treated with either lead PARP inhibitor and cisplatin in combination had significantly lower survival rates than those treated with cisplatin alone. At 10 µM, the combination showed more significant cell survival reduction, suggesting greater inhibition of PARP increases lethality, particularly in HeLa and PC-3 cell lines at 96 h and beyond.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-24"},"PeriodicalIF":3.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846216","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

Novel isatin conjugates endowed with analgesic and anti-inflammatory properties: design, synthesis and biological evaluation. 具有镇痛和抗炎特性的新型靛红共轭物：设计、合成和生物学评价。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-12-16 DOI: 10.1080/17568919.2024.2437981

LaVauria D Brown, Adel S Girgis, Shruti Patel, Nermin Samir, Mona F Said, Anurag T K Baidya, Rajnish Kumar, Jade Moore, Anshuman Khadanga, Rajeev Sakhuja, Siva S Panda

{"title":"Novel isatin conjugates endowed with analgesic and anti-inflammatory properties: design, synthesis and biological evaluation.","authors":"LaVauria D Brown, Adel S Girgis, Shruti Patel, Nermin Samir, Mona F Said, Anurag T K Baidya, Rajnish Kumar, Jade Moore, Anshuman Khadanga, Rajeev Sakhuja, Siva S Panda","doi":"10.1080/17568919.2024.2437981","DOIUrl":"https://doi.org/10.1080/17568919.2024.2437981","url":null,"abstract":"Aims: This study aimed to develop novel molecular hybrid conjugates integrating isatin, rhodanine, and phthalimide pharmacophores to create effective analgesic and anti-inflammatory agents with improved safety profiles over existing treatments.Materials & methods: A series of hybrid conjugates (4a - l) were synthesized and evaluated through in vitro and in vivo biological assays. The most promising compound, 4c, underwent extensive pharmacological and toxicological evaluations. Molecular docking, molecular dynamics simulations, and 2D-QSAR studies were performed to elucidate the mechanism of action and validate the experimental findings.Results: Compound 4c exhibited potent analgesic and anti-inflammatory activity, effectively inhibiting COX-2 and pro-inflammatory cytokines (IL-6 and TNF-α). Its superior selectivity index (SI) was 1.11 compared to 0.67 for indomethacin. It demonstrated an ulcer index of 2.9 versus 10.23 for indomethacin, indicating reduced gastrointestinal toxicity. Molecular docking simulations revealed a strong binding affinity with COX-2 (-9.832 kcal/mol), and molecular dynamics confirmed the stability of the COX-2 complex.Conclusions: Compound 4c emerged as a promising lead candidate for developing safer and more effective anti-inflammatory and analgesic agents. Its robust efficacy, safety profile, and computational validation highlight its potential for further optimization in therapeutic applications.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-15"},"PeriodicalIF":3.2,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828135","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

Novel bis-benzimidazole-triazole hybrids: anticancer study, in silico approaches, and mechanistic investigation.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-12-13 DOI: 10.1080/17568919.2024.2437980

Moataz A Soliman, Hany E A Ahmed, Elsayed H Eltamany, Ahmed T A Boraei, Ateyatallah Aljuhani, Samir A Salama, Read Alghamdi, Ahmed K B Aljohani, Mohammed Almaghrabi, Mohamed R Aouad

{"title":"Novel bis-benzimidazole-triazole hybrids: anticancer study, in silico approaches, and mechanistic investigation.","authors":"Moataz A Soliman, Hany E A Ahmed, Elsayed H Eltamany, Ahmed T A Boraei, Ateyatallah Aljuhani, Samir A Salama, Read Alghamdi, Ahmed K B Aljohani, Mohammed Almaghrabi, Mohamed R Aouad","doi":"10.1080/17568919.2024.2437980","DOIUrl":"https://doi.org/10.1080/17568919.2024.2437980","url":null,"abstract":"Aim: Benzimidazole-triazole conjugates are very active hotspot for design and synthesis of promising anticancer agents. The target analogs showed potent and selective cytotoxicity over different cancer cell lines for breast and lung ones.Materials & methods: A new series of bis-1,4-disubstituted-1,2,3-triazoles moieties conjugated with a 2-mercapto-benzimidazole 4a-h and 7a-g was synthesized via the click cycloaddition (CuAAC) reaction. The synthesized triazoles were characterized using several spectroscopic tools. In addition, they were tested against variable cell lines representing different cancer types; HepG-2, MCF-7, HCT-116, and A-549. Computational experiments were introduced for understanding their structure-activity relationships.Results & conclusion: The data revealed the outperformance of 7a-g analogs over 4a-h one with very effective IC50 values; 4-13 µg/mL compared to the reference drugs. Moreover, detailed mechanistic analyses showed potent Aurora-A Kinase expression for the most active analogs 7a and 7d exhibiting IC50; 3.5 and 5.3 over the control cells 8 ng/mL respectively. Additionally, based on their Aurora-A Kinase inhibitory activity, compound 7a was promising in apoptosis induction and cell cycle arrest. Molecular docking studies with Aurora-A Kinase revealed binding behaviors similar to the co-crystallized ligand sunitinib. Finally, this scaffold exhibits cytotoxic activity via apoptosis, enzyme downregulation, and suppression of cell division.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-15"},"PeriodicalIF":3.2,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817736","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 new coumarin derivatives and assessment of their antimicrobial efficacy.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-12-12 DOI: 10.1080/17568919.2024.2437974

Basma Saad Baaiu, Nashwa M Saleh, Abdulrahman Faraj Alshref Aldirsi, Anhar Abdel-Aziem

{"title":"Synthesis of new coumarin derivatives and assessment of their antimicrobial efficacy.","authors":"Basma Saad Baaiu, Nashwa M Saleh, Abdulrahman Faraj Alshref Aldirsi, Anhar Abdel-Aziem","doi":"10.1080/17568919.2024.2437974","DOIUrl":"https://doi.org/10.1080/17568919.2024.2437974","url":null,"abstract":"Aim: Developing new antimicrobial agents in response to the urgent challenge of antimicrobial resistance.Methods: Synthesis of the targeted coumarins, elucidation of their structures using spectroscopic tools, and investigation of their antimicrobial activity.Results: Coumarin-pyrazole 11 with CF3 in the 3-position of the pyrazole ring displayed the lowest minimum inhibitory concentrations (MICs) and the minimum bactericidal concentrations (MBCs) with values of 1.95 and 15.6 µg/ml, respectively, against Bacillus pumilis. In addition, it exhibited the best inhibitory activity against Saccharomyces cerevisiae (MIC = 3.91 µg/ml) compared to the rest of the derivatives (7.81-62.5 µg/ml). Surprisingly, coumarin 14 with the S-CH3 group had higher ability to inhibit the Staphylococcus faecalis strain with an MIC value of 1.95 µg/ml, which is twice that of penicillin G (MIC = 3.91 µg/ml). At the same time, compounds 6, 8, 11, 16, and penicillin G showed similar activity with an MIC value of 3.91 µg/ml against Staphylococcus faecalis. Also, the lowest MIC value (3.91 µg/ml) was obtained for S-CH3 derivative 14 against Enterobacter cloacae. Coumarins 14 and 1,3,4-thiadiazine derivative 6 recorded the lowest MBC (15.6 µg/ml) against Escherichia coli.Conclusion: Finally, it can be concluded that some designed coumarins have a high potential to act as potent antimicrobial agents. Some of them displayed higher efficacy than or equal to the reference drug.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-10"},"PeriodicalIF":3.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812363","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

Advances in antitumor effects of pterostilbene and its derivatives.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-12-10 DOI: 10.1080/17568919.2024.2435251

Xin Yu, Mengzhen Xu, Ziye Gao, Haixing Guan, Qingjun Zhu

引用次数: 0

New thiazolidin-4-ones as anti-cervical cancer agents targeting EGFR: design, synthesis, and computational studies.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-12-09 DOI: 10.1080/17568919.2024.2437976

Wafa A Bawazir, Nesreen S Ahmed, Somaia S Abd El-Karim, Ahmed F El-Sayed, Manal M Anwar

{"title":"New thiazolidin-4-ones as anti-cervical cancer agents targeting EGFR: design, synthesis, and computational studies.","authors":"Wafa A Bawazir, Nesreen S Ahmed, Somaia S Abd El-Karim, Ahmed F El-Sayed, Manal M Anwar","doi":"10.1080/17568919.2024.2437976","DOIUrl":"https://doi.org/10.1080/17568919.2024.2437976","url":null,"abstract":"Aim: A new series of 3,4-dihydronaphthalen-1(2 h)-ylidene)hydrazineylidene)-5-substituted thiazolidin-4-one derivatives were designed and synthesized.Results & methodology: The new compounds were screened for in vitro antitumor activity against Hela cancer cell line. The compounds 7b, 7 h, and 7i produced more potent cytotoxicity than doxorubicin with IC50 values of 1.83 ± 0.1, 2.54 ± 0.14, 2.75 ± 0.15, and 3.63 ± 0.2 μM, respectively. They also showed a promising safety profile against WI-38 normal cells. In addition, compound 7b produced a promising multi-kinase inhibition against EGFR (WT) while being very selective toward the mutant forms (L858R and T790M) with IC50 values of 0.099 ± 0.006, 0.064 ± 0.006, and 0.026 ± 0.007 μM, respectively, in comparison to gefitinib and osimertinib. A study of the cell cycle in Hela cells showed that 7b arrests cell cycle in the pre-G1 phase and causes early and late apoptosis. Eventually, the molecular docking results showed that 7b had good-binding interactions with EGFRWT, EGFRL858R, and EGFRT790M.Conclusion: Compound 7b was predicted to have promising oral absorption, good drug-likeness, and low toxicity risks in humans. Moreover, MD simulations confirmed the stable complexes of 7b with EGFRWT, EGFRL858R, and EGFRT790M (with RMSD 0.12-0.35 nm, RMSF 0.2-0.55 nm, SASA 140-150, and Rg 1.80-2.00 nm).","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-17"},"PeriodicalIF":3.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800166","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

In-vitro and in-silico assessment of thiazole-thiazolidinone derivatives as selective inhibitors of urease and α-glucosidase.

IF 3.2 4区医学

Future medicinal chemistry Pub 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":"https://doi.org/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":"1-10"},"PeriodicalIF":3.2,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0