Pub Date : 2024-09-24DOI: 10.1080/17568919.2024.2400982
Hemanathan Elango, Rabindra Nath Das, Abhijit Saha
Telomeres, crucial for chromosomal integrity, have been related to aging and cancer formation, mainly through regulating G-quadruplex structures. G-quadruplexes are structural motifs that can arise as secondary structures of nucleic acids, especially in guanine-rich DNA and RNA regions. Targeting these structures by small compounds shows promise in the selective suppression of cell growth, opening up novel possibilities for anticancer treatment. A comprehensive investigation of the many structural forms of G-quadruplex ligands is required to create ground-breaking anticancer drugs. Recent research into using specific benzimidazole molecules in stabilizing telomeric DNA into G-quadruplex structures has highlighted their ability to influence oncogene expression and demonstrate antiproliferative characteristics against cancer cells. This review describes the benzimidazole derivative, designed to enhance the stability of the G-quadruplex structure DNA to suppress the activity of telomerase enzyme, exhibiting promising potential for anticancer therapy.
端粒对染色体的完整性至关重要,它与衰老和癌症的形成有关,主要是通过调节 G 型四联体结构来实现的。G 型四联体是核酸的二级结构,尤其是在富含鸟嘌呤的 DNA 和 RNA 区域。用小分子化合物靶向这些结构有望选择性地抑制细胞生长,为抗癌治疗提供了新的可能性。要研制出突破性的抗癌药物,就必须对 G-四叠体配体的多种结构形式进行全面研究。最近对使用特定苯并咪唑分子将端粒 DNA 稳定为 G-四联体结构的研究突出表明,它们能够影响癌基因的表达,并显示出对癌细胞的抗增殖特性。本综述介绍了苯并咪唑衍生物,这种衍生物旨在增强 G 型四联结构 DNA 的稳定性,从而抑制端粒酶的活性,在抗癌治疗方面具有广阔的前景。
{"title":"Benzimidazole-based small molecules as anticancer agents targeting telomeric G-quadruplex and inhibiting telomerase enzyme.","authors":"Hemanathan Elango, Rabindra Nath Das, Abhijit Saha","doi":"10.1080/17568919.2024.2400982","DOIUrl":"https://doi.org/10.1080/17568919.2024.2400982","url":null,"abstract":"<p><p>Telomeres, crucial for chromosomal integrity, have been related to aging and cancer formation, mainly through regulating G-quadruplex structures. G-quadruplexes are structural motifs that can arise as secondary structures of nucleic acids, especially in guanine-rich DNA and RNA regions. Targeting these structures by small compounds shows promise in the selective suppression of cell growth, opening up novel possibilities for anticancer treatment. A comprehensive investigation of the many structural forms of G-quadruplex ligands is required to create ground-breaking anticancer drugs. Recent research into using specific benzimidazole molecules in stabilizing telomeric DNA into G-quadruplex structures has highlighted their ability to influence oncogene expression and demonstrate antiproliferative characteristics against cancer cells. This review describes the benzimidazole derivative, designed to enhance the stability of the G-quadruplex structure DNA to suppress the activity of telomerase enzyme, exhibiting promising potential for anticancer therapy.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344580","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}
Aim: To synthesize and evaluate the antimalarial and antioxidant activities of novel organotellurium (IV) thiophene-based complexes.Materials & methods: Synthesized complexes were characterized using NMR, IR and mass spectrometry. Their biological activities were assessed using in vitro assays and molecular docking studies.Results: The complexes exhibited significant antimalarial activity against Plasmodium falciparum, with the highest activity observed for complexes 5b and 5e. ADMET properties confirmed their potential as therapeutic agents.
目的:合成并评估新型有机碲(IV)噻吩基复合物的抗疟和抗氧化活性:使用核磁共振、红外和质谱对合成的复合物进行表征。材料与方法:利用核磁共振、红外光谱和质谱对合成的复合物进行了表征,并利用体外试验和分子对接研究对其生物活性进行了评估:结果:复合物对恶性疟原虫具有明显的抗疟活性,其中复合物 5b 和 5e 的活性最高。ADMET 特性证实了它们作为治疗剂的潜力。
{"title":"Organotellurium (IV) complexes as anti-malarial agents: synthesis, characterization and computational insights.","authors":"Anisha Bhardwaj, Amit Dubey, Aisha Tufail, Nasir Tufail, Manish Kumar, Sapana Garg","doi":"10.1080/17568919.2024.2401310","DOIUrl":"https://doi.org/10.1080/17568919.2024.2401310","url":null,"abstract":"<p><p><b>Aim:</b> To synthesize and evaluate the antimalarial and antioxidant activities of novel organotellurium (IV) thiophene-based complexes.<b>Materials & methods:</b> Synthesized complexes were characterized using NMR, IR and mass spectrometry. Their biological activities were assessed using <i>in vitro</i> assays and molecular docking studies.<b>Results:</b> The complexes exhibited significant antimalarial activity against <i>Plasmodium falciparum</i>, with the highest activity observed for complexes 5b and 5e. ADMET properties confirmed their potential as therapeutic agents.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142283281","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 : 2024-09-23DOI: 10.1080/17568919.2024.2401311
Hamidullah, Aftab Alam, Ahmed A Elhenawy, Mumtaz Ali, Abdul Latif, Ajmal Khan, Ahmed Al-Harrasi, Manzoor Ahmad
Aim: In light of various biological activities of benzimidazole and azines, this study focuses on reporting novel derivatives of benzimidazole nucleus.Methods: Twenty novel azines of benzimidazole were synthesized, characterized and tested for in vitro urease inhibitory activity.Results: All these derivatives showed excellent to good inhibition in the range of IC50 values 14.21 ± 1.87 to 76.11 ± 1.81 μM by comparing with standard thiourea 21.14 ± 0.42 μM. Docking studies were performed for the targeted benzimidazole derivatives to understand the binding mechanics. The results indicated higher binding efficacy compared with the reference inhibitor.Conclusion: This work identifies potential lead candidates for novel urease inhibitors, which with industrial support may be harnessed for the development of new drugs.
{"title":"Novel benzimidazole-based azine derivatives as potent urease inhibitors: synthesis, <i>in vitro</i> and <i>in silico</i> approach.","authors":"Hamidullah, Aftab Alam, Ahmed A Elhenawy, Mumtaz Ali, Abdul Latif, Ajmal Khan, Ahmed Al-Harrasi, Manzoor Ahmad","doi":"10.1080/17568919.2024.2401311","DOIUrl":"https://doi.org/10.1080/17568919.2024.2401311","url":null,"abstract":"<p><p><b>Aim:</b> In light of various biological activities of benzimidazole and azines, this study focuses on reporting novel derivatives of benzimidazole nucleus.<b>Methods:</b> Twenty novel azines of benzimidazole were synthesized, characterized and tested for <i>in vitro</i> urease inhibitory activity.<b>Results:</b> All these derivatives showed excellent to good inhibition in the range of IC<sub>50</sub> values 14.21 ± 1.87 to 76.11 ± 1.81 μM by comparing with standard thiourea 21.14 ± 0.42 μM. Docking studies were performed for the targeted benzimidazole derivatives to understand the binding mechanics. The results indicated higher binding efficacy compared with the reference inhibitor.<b>Conclusion:</b> This work identifies potential lead candidates for novel urease inhibitors, which with industrial support may be harnessed for the development of new drugs.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142283280","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 : 2024-09-20DOI: 10.1080/17568919.2024.2401313
Anum Masood, Mohsin Abbas Khan, Mashooq A Bhat, Breena Awan, Ramsha Hanif, Asim Raza, Saharish Khaliq, Javaid Ahmed, Farhat Ullah
Aim: Calcium channel antagonists are of considerable interest in treating elevated blood pressure and its pathologies.Materials & methods: Schiff base derivatives of amlodipine were produced to check its urease inhibition potentials as well antibacterial and antioxidant activities. Structural illustration along with chemical characterization were achieved by spectral techniques (1H NMR, FTIR, 13C NMR) and docking studies also performed.Results & conclusion: 3g displayed remarkable anti-hypertensive activity compared with parent drug. 3b, 3f and 3g showed urease inhibition potentials. These compounds can aid as lead for further investigations since they exhibited comparable or superior interactions.
{"title":"Exploring biological activities of novel Schiff bases derived from amlodipine and <i>in silico</i> molecular modeling studies.","authors":"Anum Masood, Mohsin Abbas Khan, Mashooq A Bhat, Breena Awan, Ramsha Hanif, Asim Raza, Saharish Khaliq, Javaid Ahmed, Farhat Ullah","doi":"10.1080/17568919.2024.2401313","DOIUrl":"https://doi.org/10.1080/17568919.2024.2401313","url":null,"abstract":"<p><p><b>Aim:</b> Calcium channel antagonists are of considerable interest in treating elevated blood pressure and its pathologies.<b>Materials & methods:</b> Schiff base derivatives of amlodipine were produced to check its urease inhibition potentials as well antibacterial and antioxidant activities. Structural illustration along with chemical characterization were achieved by spectral techniques (<sup>1</sup>H NMR, FTIR, <sup>13</sup>C NMR) and docking studies also performed.<b>Results & conclusion:</b> 3g displayed remarkable anti-hypertensive activity compared with parent drug. 3b, 3f and 3g showed urease inhibition potentials. These compounds can aid as lead for further investigations since they exhibited comparable or superior interactions.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142283278","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 : 2024-09-20DOI: 10.1080/17568919.2024.2401312
Daniel P Radin, Sheng Zhong, Rok Cerne, Mohammed Shoaib, Jeffrey M Witkin, Arnold Lippa
Aim: AMPA-glutamate receptor (AMPAR) dysfunction mediates multiple neurological/neuropsychiatric disorders. Ampakines bind AMPARs and allosterically enhance glutamate-elicited currents. This report describes the activity of the water-soluble ampakine CX1942 prodrug and the active moiety CX1763.Results: CX1763 and CX1942 enhance synaptic transmission in hippocampi of rats. CX1763 increases attention in the 5CSRTT in rats and reduces amphetamine-induced hyperactivity in mice. CX1942 potently reverses opioid-induced respiratory depression in rats. CX1942/CX1763 was effective at 2.5-10 mg/kg. CX1763 lacked epileptogenicity up to 1500 mg/kg in rats.Conclusion: These data document that CX1942 and CX1763 are active and without prominent side effects in multiple pre-clinical assays. CX1942 could serve as a prodrug for CX1763 with the advantage of high water solubility as in an intravenous formulation.
{"title":"Preclinical characterization of a water-soluble low-impact ampakine prodrug, CX1942 and its active moiety, CX1763.","authors":"Daniel P Radin, Sheng Zhong, Rok Cerne, Mohammed Shoaib, Jeffrey M Witkin, Arnold Lippa","doi":"10.1080/17568919.2024.2401312","DOIUrl":"https://doi.org/10.1080/17568919.2024.2401312","url":null,"abstract":"<p><p><b>Aim:</b> AMPA-glutamate receptor (AMPAR) dysfunction mediates multiple neurological/neuropsychiatric disorders. Ampakines bind AMPARs and allosterically enhance glutamate-elicited currents. This report describes the activity of the water-soluble ampakine CX1942 prodrug and the active moiety CX1763.<b>Results:</b> CX1763 and CX1942 enhance synaptic transmission in hippocampi of rats. CX1763 increases attention in the 5CSRTT in rats and reduces amphetamine-induced hyperactivity in mice. CX1942 potently reverses opioid-induced respiratory depression in rats. CX1942/CX1763 was effective at 2.5-10 mg/kg. CX1763 lacked epileptogenicity up to 1500 mg/kg in rats.<b>Conclusion:</b> These data document that CX1942 and CX1763 are active and without prominent side effects in multiple pre-clinical assays. CX1942 could serve as a prodrug for CX1763 with the advantage of high water solubility as in an intravenous formulation.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142283282","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}
Aim: Elevated levels of amylase in the blood, known as hyperamylasemia, have been correlated with diabetes and cancer. To investigate the impact of hyperamylasemia on cellular proliferation, it is imperative to design dual inhibitors targeting both α-amylase activity and cancer progression.Materials & methods: Naphthoquinone fused diazepines have been synthesized using multicomponent reaction with high Eco-score of 87 and evaluated for bio efficacy using antioxidant and α-amylase inhibition assay. A correlation between diabetes and cancer has been established via preliminary screening against A549 based lung cancer cell line at 5 μM.Results & conclusion: Compound 4b exhibited superior anti-oxidant and α-amylase inhibitory potential over butylated hydroxytoluene (BHT) and acarbose, respectively with uncompetitive mode of inhibition. Compounds possessing more than 50 % inhibition were then investigated for their IC50 against A549 (Lung cancer), and Breast cancer (MCF-7 and MDA-MB-231) cells. Among all, compound 4p has been selected for further studies, as it demonstrated significant cytotoxicity, while compound 4b showed no effect on AKT gene expression but upregulated IGF-1R gene expression, suggesting a role in managing diabetes. Compound 4p exhibited the ability to decrease AKT expression and increase IGF-1R expression, indicating its potential for treating both diabetes and cancer.
{"title":"Naphthoquinone fused diazepines targeting hyperamylasemia: potential therapeutic agents for diabetes and cancer.","authors":"Sandhya Chahal, Payal Rani, Rajvir Singh, Gaurav Joshi, Roshan Kumar, Parvin Kumar, Deepak Wadhwa, Devender Singh, Jayant Sindhu","doi":"10.1080/17568919.2024.2400968","DOIUrl":"https://doi.org/10.1080/17568919.2024.2400968","url":null,"abstract":"<p><p><b>Aim:</b> Elevated levels of amylase in the blood, known as hyperamylasemia, have been correlated with diabetes and cancer. To investigate the impact of hyperamylasemia on cellular proliferation, it is imperative to design dual inhibitors targeting both α-amylase activity and cancer progression.<b>Materials & methods:</b> Naphthoquinone fused diazepines have been synthesized using multicomponent reaction with high Eco-score of 87 and evaluated for bio efficacy using antioxidant and α-amylase inhibition assay. A correlation between diabetes and cancer has been established <i>via</i> preliminary screening against A549 based lung cancer cell line at 5 μM.<b>Results & conclusion:</b> Compound <b>4b</b> exhibited superior anti-oxidant and α-amylase inhibitory potential over butylated hydroxytoluene (BHT) and acarbose, respectively with uncompetitive mode of inhibition. Compounds possessing more than 50 % inhibition were then investigated for their IC<sub>50</sub> against A549 (Lung cancer), and Breast cancer (MCF-7 and MDA-MB-231) cells. Among all, compound <b>4p</b> has been selected for further studies, as it demonstrated significant cytotoxicity, while compound <b>4b</b> showed no effect on <i>AKT</i> gene expression but upregulated <i>IGF-1R</i> gene expression, suggesting a role in managing diabetes. Compound <b>4p</b> exhibited the ability to decrease <i>AKT</i> expression and increase <i>IGF-1R</i> expression, indicating its potential for treating both diabetes and cancer.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142283279","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 : 2024-09-20DOI: 10.1080/17568919.2024.2385295
Asmaa Aboelnaga, Eman El-Sayed Ebead, Ekhlass Nassar, Mohamed M Naguib, Mahmoud F Ismail
Aim: This work explores the eco-friendly synthesis of various heterocycles from a piperidine-based compound (1) and explore their potential as antitumor agents.Materials & methods: Ultrasonic irradiation was used to synthesize heterocycles like pyridone, thiophene and coumarin, with computational tools analyzing stability and biological interactions.Results: Compounds 9 and 14 exhibit strong cytotoxic activity, surpassing doxorubicin. Compounds 2, 6, 10 and 13 exhibited intermediate activity, while compounds 3, 7 and 12 had minimal effects. Docking studies suggest potential ADORA1 receptor interaction. Computational tools analyze stability and interaction with biological systems, revealing potential antitumor mechanisms.Conclusion: Green synthesis of diverse heterocycles yielded potent antitumor agents (compounds 9 & 14). DFT and Docking studies suggest interaction with ADORA1 receptor, a potential mechanism.
{"title":"Ultrasonic-assisted synthesis and antitumor evaluation of novel variant heterocyclic compounds based on piperidine ring.","authors":"Asmaa Aboelnaga, Eman El-Sayed Ebead, Ekhlass Nassar, Mohamed M Naguib, Mahmoud F Ismail","doi":"10.1080/17568919.2024.2385295","DOIUrl":"https://doi.org/10.1080/17568919.2024.2385295","url":null,"abstract":"<p><p><b>Aim:</b> This work explores the eco-friendly synthesis of various heterocycles from a piperidine-based compound (<b>1</b>) and explore their potential as antitumor agents.<b>Materials & methods:</b> Ultrasonic irradiation was used to synthesize heterocycles like pyridone, thiophene and coumarin, with computational tools analyzing stability and biological interactions.<b>Results:</b> Compounds <b>9</b> and <b>14</b> exhibit strong cytotoxic activity, surpassing doxorubicin. Compounds <b>2</b>, <b>6</b>, <b>10</b> and <b>13</b> exhibited intermediate activity, while compounds <b>3</b>, <b>7</b> and <b>12</b> had minimal effects. Docking studies suggest potential ADORA1 receptor interaction. Computational tools analyze stability and interaction with biological systems, revealing potential antitumor mechanisms.<b>Conclusion:</b> Green synthesis of diverse heterocycles yielded potent antitumor agents (compounds <b>9</b> & <b>14</b>). DFT and Docking studies suggest interaction with ADORA1 receptor, a potential mechanism.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142283284","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 : 2024-09-19DOI: 10.1080/17568919.2024.2394016
Kaito Ohta, Hiromi Ii, Mei Takahashi, Chiami Moyama, Shota Ando, Masaya Mori, Maho Masuda, Hisanori Nambu, Susumu Nakata, Naoto Kojima
Aim: Certain cancer cells depend on oxidative phosphorylation for survival; thus, inhibiting this process may be a promising treatment strategy. This study explored the structure-activity relationships of the mitochondrial inhibitor N-ethylene glycol-comprising alkyl thiophene-3-carboxamide 3.Methods & results: We synthesized and evaluated 13 analogs (5a-m) with different ethylene glycol units, heterocycles and connecting groups for their growth-inhibitory effects on A549 non-small cell lung cancer cells. We found that increasing the number of ethylene glycol units significantly enhanced inhibitory activity. Some analogs activated adenosine monophosphate-activated protein kinase, similar to 3. Notably, analog 5e, which contains tetraethylene glycol units, significantly inhibited tumor growth in vivo.Conclusion: Analog 5 may be a potential therapeutic agent for non-small cell lung cancer treatment.
目的:某些癌细胞的存活依赖于氧化磷酸化;因此,抑制这一过程可能是一种很有前景的治疗策略。本研究探讨了线粒体抑制剂 N-乙二醇-含烷基噻吩-3-甲酰胺 3 的结构-活性关系:我们合成并评估了13种具有不同乙二醇单元、杂环和连接基团的类似物(5a-m)对A549非小细胞肺癌细胞的生长抑制作用。我们发现,增加乙二醇单元的数量可显著增强抑制活性。一些类似物激活了单磷酸腺苷激活的蛋白激酶,与 3 类似。值得注意的是,含有四甘醇单位的类似物 5e 能显著抑制体内肿瘤的生长:结论:类似物 5 可能是治疗非小细胞肺癌的潜在药物。
{"title":"Structure-activity relationships study of <i>N</i>-ethylene glycol-comprising alkyl heterocyclic carboxamides against A549 lung cancer cells.","authors":"Kaito Ohta, Hiromi Ii, Mei Takahashi, Chiami Moyama, Shota Ando, Masaya Mori, Maho Masuda, Hisanori Nambu, Susumu Nakata, Naoto Kojima","doi":"10.1080/17568919.2024.2394016","DOIUrl":"https://doi.org/10.1080/17568919.2024.2394016","url":null,"abstract":"<p><p><b>Aim:</b> Certain cancer cells depend on oxidative phosphorylation for survival; thus, inhibiting this process may be a promising treatment strategy. This study explored the structure-activity relationships of the mitochondrial inhibitor <i>N</i>-ethylene glycol-comprising alkyl thiophene-3-carboxamide <b>3</b>.<b>Methods & results:</b> We synthesized and evaluated 13 analogs (<b>5a</b>-<b>m</b>) with different ethylene glycol units, heterocycles and connecting groups for their growth-inhibitory effects on A549 non-small cell lung cancer cells. We found that increasing the number of ethylene glycol units significantly enhanced inhibitory activity. Some analogs activated adenosine monophosphate-activated protein kinase, similar to <b>3</b>. Notably, analog <b>5e</b>, which contains tetraethylene glycol units, significantly inhibited tumor growth <i>in vivo</i>.<b>Conclusion:</b> Analog <b>5</b> may be a potential therapeutic agent for non-small cell lung cancer treatment.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142283283","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 : 2024-09-19DOI: 10.1080/17568919.2024.2393570
Ebrahim Saeedian Moghadam, Abdullah Mohammed Al-Sadi, Mahdis Sadeghi Moghadam, Bahareh Bayati, Meysam Talebi, Massoud Amanlou, Mohsen Amini, Raid Abdel-Jalil
Aim: A series of benzimidazole-acrylonitrile derivatives TM1-TM53 were designed with urease inhibition approach.Materials & methods:TM1-TM53 were synthesized and characterized (1H Nuclear Magnetic Resonance (NMR), 13C NMR, Mass Spectroscopy (MS) and IR) and subjected to urease inhibition assay using commercial assay kit. A molecular docking study was also performed using Autodock tool software.Results: Except six compounds, target molecules exhibited a higher urease inhibition effect (IC50: 1.22-28.45 μM) than hydroxyurea (IC50: 100 μM). kinetic study on TM11, clarified its mode of action as a mixed inhibitor. A molecular docking study on TM6, TM11 and TM21, was performed and the results showed the main residues inside the active site of the enzyme. All TM1-TM53 were also studied in silico using molecular docking techniques to evaluate their potential to inhibit succinate dehydrogenase in comparison to fluxapyroxad as standard. Docking study revealed the high potential of TM1-TM53 as a fungicides.Conclusion: Obtained results exhibited the high activity of benzimidazole-acrylonitrile derivatives as urease inhibitors and their possible potential as fungicide agents. So, it will be beneficial to do more bioactivity investigation on this family of compounds.
{"title":"Benzimidazole-acrylonitrile hybrid derivatives act as potent urease inhibitors with possible fungicidal activity.","authors":"Ebrahim Saeedian Moghadam, Abdullah Mohammed Al-Sadi, Mahdis Sadeghi Moghadam, Bahareh Bayati, Meysam Talebi, Massoud Amanlou, Mohsen Amini, Raid Abdel-Jalil","doi":"10.1080/17568919.2024.2393570","DOIUrl":"https://doi.org/10.1080/17568919.2024.2393570","url":null,"abstract":"<p><p><b>Aim:</b> A series of benzimidazole-acrylonitrile derivatives <b>TM1-TM53</b> were designed with urease inhibition approach.<b>Materials & methods:</b> <b>TM1-TM53</b> were synthesized and characterized (<sup>1</sup>H Nuclear Magnetic Resonance (NMR), <sup>13</sup>C NMR, Mass Spectroscopy (MS) and IR) and subjected to urease inhibition assay using commercial assay kit. A molecular docking study was also performed using Autodock tool software.<b>Results:</b> Except six compounds, target molecules exhibited a higher urease inhibition effect (IC<sub>50</sub>: 1.22-28.45 μM) than hydroxyurea (IC<sub>50</sub>: 100 μM). kinetic study on <b>TM11</b>, clarified its mode of action as a mixed inhibitor. A molecular docking study on <b>TM6</b>, <b>TM11</b> and <b>TM21</b>, was performed and the results showed the main residues inside the active site of the enzyme. All <b>TM1-TM53</b> were also studied <i>in silico</i> using molecular docking techniques to evaluate their potential to inhibit succinate dehydrogenase in comparison to fluxapyroxad as standard. Docking study revealed the high potential of <b>TM1-TM53</b> as a fungicides.<b>Conclusion:</b> Obtained results exhibited the high activity of benzimidazole-acrylonitrile derivatives as urease inhibitors and their possible potential as fungicide agents. So, it will be beneficial to do more bioactivity investigation on this family of compounds.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142283277","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}