Aim: The extensive utilization of 2-phenylbenzothiazole due to their wide array of biological activities, particularly in cancer therapy, has caused great attention to explore more potent derivatives.Materials & methods: We report the synthesis of 2-phenylbenzothiazole tagged 1,2,3-triaozle (8) through Cu(I)-catalyzed cycloaddition of alkyne side chain with aryl-substituted azides.Results: The in vitro experiments, using MTT and 99mTc-MIBI cell uptake methods, demonstrated the remarkable anticancer activity of these compounds against A549, SKOV3 and MCF7 cell lines.Conclusion: Compounds 8b, 8f and 8i possessed high cytotoxic activity as compared with doxorubicin. Compound 8g has a similar inhibitory effect on the proliferation of breast cancer cells as doxorubicin. In silico study indicated that compound 8 would be a good lead for the development of new potent anticancer agents.
{"title":"Synthesis, cytotoxicity and <sup>99m</sup>Tc-MIBI tumor cell uptake evaluation of 2-phenylbenzothiazole tagged triazole derivatives.","authors":"Marzieh Aghaei Khouzani, Zohreh Noaparast, Tina Asadi, Sajad Saeidi, Alireza Heidarnia, Behnoush Hamzeh Moghadam, Hanieh Mosavi Kia, Seyedeh Mahdieh Hashemi, Mohammad Mahdavi","doi":"10.1080/17568919.2024.2389771","DOIUrl":"https://doi.org/10.1080/17568919.2024.2389771","url":null,"abstract":"<p><p><b>Aim:</b> The extensive utilization of 2-phenylbenzothiazole due to their wide array of biological activities, particularly in cancer therapy, has caused great attention to explore more potent derivatives.<b>Materials & methods:</b> We report the synthesis of 2-phenylbenzothiazole tagged 1,2,3-triaozle <b>(8)</b> through Cu(I)-catalyzed cycloaddition of alkyne side chain with aryl-substituted azides.<b>Results:</b> The <i>in vitro</i> experiments, using MTT and 99mTc-MIBI cell uptake methods, demonstrated the remarkable anticancer activity of these compounds against A549, SKOV3 and MCF7 cell lines.<b>Conclusion:</b> Compounds <b>8b</b>, <b>8f</b> and <b>8i</b> possessed high cytotoxic activity as compared with doxorubicin. Compound <b>8g</b> has a similar inhibitory effect on the proliferation of breast cancer cells as doxorubicin. <i>In silico</i> study indicated that compound <b>8</b> would be a good lead for the development of new potent anticancer agents.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125344","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}
Pub Date : 2024-09-04DOI: 10.1080/17568919.2024.2389772
Ayman B Farag, Aya H Othman, Mohamed K El-Ashrey, Safinaz E-S Abbas, Tamer A Elwaie
Aim: Twenty compounds of 6-nitro-4-substituted quinazolines were synthesized.Materials & methods: The new derivatives were evaluated for their epidermal growth factor receptor (EGFR) inhibitory activity. The most potent derivatives were assessed for their cytotoxicity against colon cancer and lung cancer cells, in addition to normal fibroblast cells.Results & discussion: compound 6c showed a superior to nearly equal cytotoxicity in comparison to gefitinib, it also revealed a good safety profile. Compound 6c caused a cell cycle arrest at G2/M phase in addition to induction of apoptosis. A molecular docking study was conducted on the most active compounds to gain insights of their binding mode in the active site of EGFR enzyme besides ADME prediction of their physicochemical properties and drug likeness profile.
{"title":"New 6-nitro-4-substituted quinazoline derivatives targeting epidermal growth factor receptor: design, synthesis and <i>in vitro</i> anticancer studies.","authors":"Ayman B Farag, Aya H Othman, Mohamed K El-Ashrey, Safinaz E-S Abbas, Tamer A Elwaie","doi":"10.1080/17568919.2024.2389772","DOIUrl":"https://doi.org/10.1080/17568919.2024.2389772","url":null,"abstract":"<p><p><b>Aim:</b> Twenty compounds of 6-nitro-4-substituted quinazolines were synthesized.<b>Materials & methods:</b> The new derivatives were evaluated for their epidermal growth factor receptor (EGFR) inhibitory activity. The most potent derivatives were assessed for their cytotoxicity against colon cancer and lung cancer cells, in addition to normal fibroblast cells.<b>Results & discussion:</b> compound <b>6c</b> showed a superior to nearly equal cytotoxicity in comparison to gefitinib, it also revealed a good safety profile. Compound <b>6c</b> caused a cell cycle arrest at G2/M phase in addition to induction of apoptosis. A molecular docking study was conducted on the most active compounds to gain insights of their binding mode in the active site of EGFR enzyme besides ADME prediction of their physicochemical properties and drug likeness profile.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125342","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}
Pub Date : 2024-09-04DOI: 10.1080/17568919.2024.2389773
Van-Thinh To, Tieu-Long Phan, Bao-Vy Ngoc Doan, Phuoc-Chung Van Nguyen, Quang-Huy Nguyen Le, Hoang-Huy Nguyen, The-Chuong Trinh, Tuyen Ngoc Truong
Aims: Immune checkpoint inhibitors targeting PD-L1 are crucial in cancer research for preventing cancer cells from evading the immune system.Materials & methods: This study developed a screening model combining ANN, molecular similarity, and GNINA 1.0 docking to target PD-L1. A database of 2044 substances was compiled from patents.Results: For molecular similarity, the AVALON emerged as the most effective fingerprint, demonstrating an AUC-ROC of 0.963. The ANN model outperformed the Random Forest and Support Vector Classifier in cross-validation and external validation, achieving an average precision of 0.851 and an F1 score of 0.790. GNINA 1.0 was validated through redocking and retrospective control, achieving an AUC of 0.975.Conclusions: From 15235 DrugBank compounds, 22 candidates were shortlisted. Among which (3S)-1-(4-acetylphenyl)-5-oxopyrrolidine-3-carboxylic acid emerged as the most promising.
{"title":"Innovative virtual screening of PD-L1 inhibitors: the synergy of molecular similarity, neural networks and GNINA docking.","authors":"Van-Thinh To, Tieu-Long Phan, Bao-Vy Ngoc Doan, Phuoc-Chung Van Nguyen, Quang-Huy Nguyen Le, Hoang-Huy Nguyen, The-Chuong Trinh, Tuyen Ngoc Truong","doi":"10.1080/17568919.2024.2389773","DOIUrl":"https://doi.org/10.1080/17568919.2024.2389773","url":null,"abstract":"<p><p><b>Aims:</b> Immune checkpoint inhibitors targeting PD-L1 are crucial in cancer research for preventing cancer cells from evading the immune system.<b>Materials & methods:</b> This study developed a screening model combining ANN, molecular similarity, and GNINA 1.0 docking to target PD-L1. A database of 2044 substances was compiled from patents.<b>Results:</b> For molecular similarity, the AVALON emerged as the most effective fingerprint, demonstrating an AUC-ROC of 0.963. The ANN model outperformed the Random Forest and Support Vector Classifier in cross-validation and external validation, achieving an average precision of 0.851 and an F1 score of 0.790. GNINA 1.0 was validated through redocking and retrospective control, achieving an AUC of 0.975.<b>Conclusions:</b> From 15235 DrugBank compounds, 22 candidates were shortlisted. Among which (3<i>S</i>)-1-(4-acetylphenyl)-5-oxopyrrolidine-3-carboxylic acid emerged as the most promising.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125332","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}
Pub Date : 2024-08-29DOI: 10.1080/17568919.2024.2389764
Qiangfeng Wang, Yumeng Zhu, Junping Pei
Abnormal activation of EGFR is often associated with various malignant tumors, making it an important target for antitumor therapy. However, traditional targeted inhibitors have several limitations, such as drug resistance and side effects. Many studies have focused on the development of EGFR degraders to overcome this resistance and enhance the therapeutic effect on tumors. Proteolysis targeting chimeras (PROTAC) and Lysosome-based degradation techniques have made significant progress in degrading EGFR. This review provides a summary of the structural and function of EGFR, the resistance, particularly the research progress and activity of EGFR degraders via the proteasome and lysosome. Furthermore, this review aims to provide insights for the development of the novel EGFR degraders.
{"title":"Targeting EGFR with molecular degraders as a promising strategy to overcome resistance to EGFR inhibitors.","authors":"Qiangfeng Wang, Yumeng Zhu, Junping Pei","doi":"10.1080/17568919.2024.2389764","DOIUrl":"https://doi.org/10.1080/17568919.2024.2389764","url":null,"abstract":"<p><p>Abnormal activation of EGFR is often associated with various malignant tumors, making it an important target for antitumor therapy. However, traditional targeted inhibitors have several limitations, such as drug resistance and side effects. Many studies have focused on the development of EGFR degraders to overcome this resistance and enhance the therapeutic effect on tumors. Proteolysis targeting chimeras (PROTAC) and Lysosome-based degradation techniques have made significant progress in degrading EGFR. This review provides a summary of the structural and function of EGFR, the resistance, particularly the research progress and activity of EGFR degraders via the proteasome and lysosome. Furthermore, this review aims to provide insights for the development of the novel EGFR degraders.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142106173","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}
Pub Date : 2024-08-27DOI: 10.1080/17568919.2024.2385293
Aisha Alsfouk
Protein kinases play a key role in cellular signaling pathways including proliferation, apoptosis, inflammation and immune regulation. Therefore, targeting kinases with small molecules has emerged as a therapeutic potential in cancers and other diseases including inflammatory and autoimmune disorders. The main chemical motifs of the available small molecule kinase inhibitors are heterocyclic, nitrogen-containing and six-membered rings including pyrazine. Several potent and selective pyrazine-based kinase inhibitors have been developed and progressed into clinical trials. The data of clinical application of kinase inhibitors demonstrate good clinical activity with manageable toxicity in several relapse-resistant malignancies and severe to moderate immunological disorders. All pyrazine-based kinase inhibitors are orally active. This paper reviews the most recent kinase literature (2019-2023) related to pyrazine-based small molecule inhibitors. This review includes the FDA (Food and Drug Administration)-approved and patent agents along with their targeted kinase, scaffold, potency, selectivity profile, assignee and biological results in clinical and preclinical studies.
{"title":"Pyrazine-based small molecule kinase inhibitors: clinical applications and patent review (2019-2023).","authors":"Aisha Alsfouk","doi":"10.1080/17568919.2024.2385293","DOIUrl":"https://doi.org/10.1080/17568919.2024.2385293","url":null,"abstract":"<p><p>Protein kinases play a key role in cellular signaling pathways including proliferation, apoptosis, inflammation and immune regulation. Therefore, targeting kinases with small molecules has emerged as a therapeutic potential in cancers and other diseases including inflammatory and autoimmune disorders. The main chemical motifs of the available small molecule kinase inhibitors are heterocyclic, nitrogen-containing and six-membered rings including pyrazine. Several potent and selective pyrazine-based kinase inhibitors have been developed and progressed into clinical trials. The data of clinical application of kinase inhibitors demonstrate good clinical activity with manageable toxicity in several relapse-resistant malignancies and severe to moderate immunological disorders. All pyrazine-based kinase inhibitors are orally active. This paper reviews the most recent kinase literature (2019-2023) related to pyrazine-based small molecule inhibitors. This review includes the FDA (Food and Drug Administration)-approved and patent agents along with their targeted kinase, scaffold, potency, selectivity profile, assignee and biological results in clinical and preclinical studies.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072440","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}
Pub Date : 2024-08-19DOI: 10.1080/17568919.2024.2385292
Thiago Antonio de Sousa Cutrim, Fernando Fontes Barcelos, Leandra Martins Meireles, Poliana Aparecida Rodrigues Gazolla, Ângela Maria Almeida Lima, Róbson Ricardo Teixeira, Luiza Carvalheira Moreira, Vagner Tebaldi de Queiroz, Luiz Cláudio Almeida Barbosa, Pedro Alves Bezerra Morais, Cláudia Jorge do Nascimento, Jochen Junker, Adilson Vidal Costa, Marcio Fronza, Rodrigo Scherer
Aim: The design, synthesis, docking studies and evaluation of the in vitro antifungal and cytotoxic properties of eugenol (EUG) containing 1,2,3-triazole derivatives are reported. Most of the derivatives have not been reported.Materials & methods: The EUG derivatives were synthesized, molecular docked and tested for their antifungal activity.Results: The compounds showed potent antifungal activity against Trichophyton rubrum, associated with dermatophytosis. Compounds 2a and 2i exhibited promising results, with 2a being four-times more potent than EUG. The binding mode prediction was similar to itraconazole in the lanosterol-14-α-demethylase wild-type and G73E mutant binding sites. Additionally, the pharmacokinetic profile prediction suggests good gastrointestinal absorption and potential oral administration.Conclusion: Compound 2a is a promising antifungal agent against dermatophytosis caused by T. rubrum.
{"title":"Design, synthesis, docking studies and bioactivity evaluation of 1,2,3-triazole eugenol derivatives.","authors":"Thiago Antonio de Sousa Cutrim, Fernando Fontes Barcelos, Leandra Martins Meireles, Poliana Aparecida Rodrigues Gazolla, Ângela Maria Almeida Lima, Róbson Ricardo Teixeira, Luiza Carvalheira Moreira, Vagner Tebaldi de Queiroz, Luiz Cláudio Almeida Barbosa, Pedro Alves Bezerra Morais, Cláudia Jorge do Nascimento, Jochen Junker, Adilson Vidal Costa, Marcio Fronza, Rodrigo Scherer","doi":"10.1080/17568919.2024.2385292","DOIUrl":"https://doi.org/10.1080/17568919.2024.2385292","url":null,"abstract":"<p><p><b>Aim:</b> The design, synthesis, docking studies and evaluation of the <i>in vitro</i> antifungal and cytotoxic properties of eugenol (EUG) containing 1,2,3-triazole derivatives are reported. Most of the derivatives have not been reported.<b>Materials & methods:</b> The EUG derivatives were synthesized, molecular docked and tested for their antifungal activity.<b>Results:</b> The compounds showed potent antifungal activity against <i>Trichophyton rubrum</i>, associated with dermatophytosis. Compounds <b>2a</b> and <b>2i</b> exhibited promising results, with <b>2a</b> being four-times more potent than EUG. The binding mode prediction was similar to itraconazole in the lanosterol-14-α-demethylase wild-type and G73E mutant binding sites. Additionally, the pharmacokinetic profile prediction suggests good gastrointestinal absorption and potential oral administration.<b>Conclusion:</b> Compound <b>2a</b> is a promising antifungal agent against dermatophytosis caused by <i>T. rubrum</i>.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999722","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}
Pub Date : 2024-08-19DOI: 10.1080/17568919.2024.2385298
Abdelrahim Alqudah, Esam Qnais, Kayed Abu-Safieh, Omar Gammoh, Yousra Bseiso, Mohammed Wedyan, Mohammed Alqudah, Mohammad Alemleh, Badriyah S Alotaibi
Aim: Investigating a novel compound, DMPNP, for treating colitis in mice, a key issue in inflammatory bowel diseases (IBD). Methods: Mice with induced colitis received DMPNP (50, 100, 150 mg/kg) or sulfasalazine (SUL), evaluated via tissue assessment, Disease Activity Index (DAI), myeloperoxidase (MPO), nitric oxide (NO) levels and cytokine analysis. Results: DMPNP significantly reduced colitis symptoms, inflammation and oxidative stress at higher doses, with marked improvements in DAI, MPO, NO and cytokines, comparable to SUL results. Conclusion: DMPNP shows potent anti-inflammatory and immunomodulatory properties, indicating potential as an IBD therapeutic. Further clinical trials are suggested to validate these outcomes.
{"title":"Therapeutic potential of a novel pyrazolyl-pyridine derivative in the treatment of experimental colitis.","authors":"Abdelrahim Alqudah, Esam Qnais, Kayed Abu-Safieh, Omar Gammoh, Yousra Bseiso, Mohammed Wedyan, Mohammed Alqudah, Mohammad Alemleh, Badriyah S Alotaibi","doi":"10.1080/17568919.2024.2385298","DOIUrl":"https://doi.org/10.1080/17568919.2024.2385298","url":null,"abstract":"<p><p><b>Aim:</b> Investigating a novel compound, DMPNP, for treating colitis in mice, a key issue in inflammatory bowel diseases (IBD). <b>Methods:</b> Mice with induced colitis received DMPNP (50, 100, 150 mg/kg) or sulfasalazine (SUL), evaluated via tissue assessment, Disease Activity Index (DAI), myeloperoxidase (MPO), nitric oxide (NO) levels and cytokine analysis. <b>Results:</b> DMPNP significantly reduced colitis symptoms, inflammation and oxidative stress at higher doses, with marked improvements in DAI, MPO, NO and cytokines, comparable to SUL results. <b>Conclusion:</b> DMPNP shows potent anti-inflammatory and immunomodulatory properties, indicating potential as an IBD therapeutic. Further clinical trials are suggested to validate these outcomes.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999723","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}
Pub Date : 2024-08-17Epub Date: 2024-07-18DOI: 10.1080/17568919.2024.2366147
Fatma Ma Krakisha, Dina Ia Othman, Walaa M El Husseiny, Magda Na Nasr
Aim: A series of pyridopyrimidine derivatives 5-20 was designed, synthesized and examined for antitumor activity using four types of malignant cells.Materials & methods: Cervical cancer (HeLa), hepatic cancer (HepG-2), breast cancer (MCF-7) and colon cancer (HCT-166) cells, as well as normal human lung fibroblast cells (WI-38) were used to determine the cytotoxicity.Results: Pyrazol-1-yl pyridopyrimidine derivative 5 was found to be the most active compound against three malignant cells Hela, MCF-7 and HepG-2 with IC50 values of 9.27, 7.69 and 5.91 μM, respectively, related to standard Doxorubicin. Moreover, compounds 5 and 10 showed good inhibition against cyclin dependent kinase (CDK4/cyclin D1) and epidermal growth factor (EGFR) enzymes.
{"title":"New pyridopyrimidine derivatives as dual EGFR and CDK4/cyclin D1 inhibitors: synthesis, biological screening and molecular modeling.","authors":"Fatma Ma Krakisha, Dina Ia Othman, Walaa M El Husseiny, Magda Na Nasr","doi":"10.1080/17568919.2024.2366147","DOIUrl":"10.1080/17568919.2024.2366147","url":null,"abstract":"<p><p><b>Aim:</b> A series of pyridopyrimidine derivatives <b>5-20</b> was designed, synthesized and examined for antitumor activity using four types of malignant cells.<b>Materials & methods:</b> Cervical cancer (HeLa), hepatic cancer (HepG-2), breast cancer (MCF-7) and colon cancer (HCT-166) cells, as well as normal human lung fibroblast cells (WI-38) were used to determine the cytotoxicity.<b>Results:</b> Pyrazol-1-<i>yl</i> pyridopyrimidine derivative <b>5</b> was found to be the most active compound against three malignant cells Hela, MCF-7 and HepG-2 with IC<sub>50</sub> values of 9.27, 7.69 and 5.91 μM, respectively, related to standard Doxorubicin. Moreover, compounds <b>5</b> and <b>10</b> showed good inhibition against cyclin dependent kinase (CDK4/cyclin D1) and epidermal growth factor (EGFR) enzymes.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633145","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}
Pub Date : 2024-08-17Epub Date: 2024-06-28DOI: 10.1080/17568919.2024.2363713
Muhammad Ayaz, Syed Wadood Ali Shah, Mohammad Shoaib, Fawad Ali Shah, Fawad Ahmed
Aim: To synthesize aurone (Ar) derivatives and to demonstrate their effects against diabetes mellitus (DM) and neurodegeneration.Materials & methods: Five Ar (A-E) derivatives were synthesized, characterized by proton NMR and screened for antioxidant, anti-diabetic and anti-cholinesterase activities. They were further evaluated for neuroprotective effects in streptozotocin (STZ)-induced neurodegenerative model.Results: Among the aurone derivatives ArE demonstrated significant reversal of cognitive impairment, oxidative stress and neuroinflammation. Biochemical analysis revealed anti-diabetic and neuroprotective effects, possibly through downregulation of inflammatory markers and upregulation of antioxidant enzymes.Conclusion: Synthesized Ar (A-E) exhibits promising therapeutic potential against STZ-induced neurodegeneration and DM by modulating inflammatory and oxidative pathways, suggesting a novel avenue for disease management.
{"title":"Synthesis, characterization and biological evaluation of aurones as potential neuroprotective agents.","authors":"Muhammad Ayaz, Syed Wadood Ali Shah, Mohammad Shoaib, Fawad Ali Shah, Fawad Ahmed","doi":"10.1080/17568919.2024.2363713","DOIUrl":"10.1080/17568919.2024.2363713","url":null,"abstract":"<p><p><b>Aim:</b> To synthesize aurone (Ar) derivatives and to demonstrate their effects against diabetes mellitus (DM) and neurodegeneration.<b>Materials & methods:</b> Five Ar (<b>A-E</b>) derivatives were synthesized, characterized by proton NMR and screened for antioxidant, anti-diabetic and anti-cholinesterase activities. They were further evaluated for neuroprotective effects in streptozotocin (STZ)-induced neurodegenerative model.<b>Results:</b> Among the aurone derivatives ArE demonstrated significant reversal of cognitive impairment, oxidative stress and neuroinflammation. Biochemical analysis revealed anti-diabetic and neuroprotective effects, possibly through downregulation of inflammatory markers and upregulation of antioxidant enzymes.<b>Conclusion:</b> Synthesized Ar (<b>A-E</b>) exhibits promising therapeutic potential against STZ-induced neurodegeneration and DM by modulating inflammatory and oxidative pathways, suggesting a novel avenue for disease management.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467407","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}
Pub Date : 2024-08-17Epub Date: 2024-07-01DOI: 10.1080/17568919.2024.2366694
Dalal Nasser Binjawhar, Fawziah A Al-Salmi, Maha Ali Alghamdi, Ola A Abu Ali, Eman Fayad, Youstina William Rizzk, Nourhan M Ali, Ibrahim Mohey El-Deen, Elsayed H Eltamany
Aim: To synthesize new hybrid cinnamic acids (10a, 10b and 11) and ester derivatives (7, 8 and 9) and investigate their anti-breast cancer activities.Materials & methods: Compounds 7-11 were evaluated (in vitro) for their cytotoxic activities against the MCF-7 cell line. A flow cytometry examination was performed. Protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), topoisomerase II and caspase-9 were measured by qRT-PCR. Molecular docking studies were conducted.Results: Several components were discovered to be active, mainly component 11, which induced arrest in the cell cycle at phase S, greatly decreased the expression of Nrf2 and topoisomerase II; and upregulated the expression of caspase-9.Conclusion: The newly thiohydantoin-cinnamic acid hybrids can contribute to creating promising candidates for cancer drugs.
目的:合成新的混合肉桂酸(10a、10b 和 11)和酯衍生物(7、8 和 9),并研究它们的抗乳腺癌活性。材料与方法:在体外评估了化合物 7-11 对 MCF-7 细胞系的细胞毒性活性。进行了流式细胞术检测。通过 qRT-PCR 检测了核因子红细胞 2 相关因子 2(Nrf2)、拓扑异构酶 II 和 caspase-9 的蛋白水平。进行了分子对接研究。结果:发现了几种具有活性的成分,主要是成分 11,它诱导细胞周期停滞在 S 期,大大降低了 Nrf2 和拓扑异构酶 II 的表达,并上调了 caspase-9 的表达。结论新发现的硫代海因-肉桂酸杂交化合物有助于创造有前景的候选抗癌药物。
{"title":"<i>In vitro</i> anti-breast cancer study of hybrid cinnamic acid derivatives bearing 2-thiohydantoin moiety.","authors":"Dalal Nasser Binjawhar, Fawziah A Al-Salmi, Maha Ali Alghamdi, Ola A Abu Ali, Eman Fayad, Youstina William Rizzk, Nourhan M Ali, Ibrahim Mohey El-Deen, Elsayed H Eltamany","doi":"10.1080/17568919.2024.2366694","DOIUrl":"10.1080/17568919.2024.2366694","url":null,"abstract":"<p><p><b>Aim</b>: To synthesize new hybrid cinnamic acids (<b>10a</b>, <b>10b</b> and <b>11</b>) and ester derivatives (<b>7</b>, <b>8</b> and <b>9</b>) and investigate their anti-breast cancer activities.<b>Materials & methods:</b> Compounds <b>7-11</b> were evaluated (<i>in vitro</i>) for their cytotoxic activities against the MCF-7 cell line. A flow cytometry examination was performed. Protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), topoisomerase II and caspase-9 were measured by qRT-PCR. Molecular docking studies were conducted.<b>Results</b>: Several components were discovered to be active, mainly component <b>11</b>, which induced arrest in the cell cycle at phase S, greatly decreased the expression of Nrf2 and topoisomerase II; and upregulated the expression of caspase-9.<b>Conclusion:</b> The newly thiohydantoin-cinnamic acid hybrids can contribute to creating promising candidates for cancer drugs.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467402","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}