Medicinal Chemistry最新文献

{"title":"Pyrazolo - Pyrimidines as Targeted Anticancer Scaffolds - A Comprehensive Review.","authors":"Kesavamoorthy Kandhasamy, Remya Ramachandran Surajambika, Pradeep Kumar Velayudham","doi":"10.2174/0115734064251256231018104623","DOIUrl":"10.2174/0115734064251256231018104623","url":null,"abstract":"<p><strong>Background: </strong>Globally, cancer is the leading cause of death, which causes 10 million deaths yearly. Clinically, several drugs are used in treatment but due to drug resistance and multidrug resistance, there occurs a failure in the cancer treatment.</p><p><strong>Objectives: </strong>The present review article is a comprehensive review of pyrazole and pyrimidine hybrids as potential anticancer agents.</p><p><strong>Methods: </strong>The review comprises more than 60 research works done in this field. The efficiency of the reported pyrazolopyrimidine fused heterocyclic with their biological data and the influence of the structural aspects of the molecule have been discussed.</p><p><strong>Results: </strong>This review highlighted pyrazolo-pyrimidines as targeted anticancer agents with effect on multiple targets.</p><p><strong>Conclusion: </strong>The review will be helpful for the researchers involved in targeted drugs for cancer therapy for designing new scaffolds with pyrazolo-pyrimidine moieties.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"293-310"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54229913","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}

{"title":"Exploring the Therapeutic Marvels: A Comprehensive Review on the Biological Potential of Quinoline-5,8-Dione.","authors":"Neetu Agrawal, Dimple Bansal, Shilpi Pathak","doi":"10.2174/0115734064287677231215070816","DOIUrl":"10.2174/0115734064287677231215070816","url":null,"abstract":"<p><p>Quinoline-5,8-diones, also referred to as 5,8-quinolinediones or quinolinequinones, have been researched extensively for their antiproliferative effects, where they displayed great results. Other than anticancer, they exhibit multiple activities such as antimalarial, antiviral, antibacterial, and antifungal activities. Natural quinolinequinones have also been known for their significant activities. The review highlights the diverse biological activities exhibited by synthetic quinoline- 5,8-diones over the past two decades. Continued research in this field is warranted to fully exploit the therapeutic potential of these intriguing compounds and their derivatives for future drug development. By comprehensively evaluating the therapeutic applications and biological activities of quinoline-5,8-dione derivatives, this review endeavors to provide researchers and practitioners with a valuable resource that will foster informed decision-making and inspire further investigations into harnessing the immense potential of this intriguing scaffold for the benefit of human health.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"385-396"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139087364","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}

{"title":"A Profound Insight into the Structure-activity Relationship of Ubiquitous Scaffold Piperazine: An Explicative Review.","authors":"Jasmine Chaudhary, Vishal Sharma, Akash Jain, Diksha Sharma, Bhawna Chopra, Ashwani K Dhingra","doi":"10.2174/0115734064244117230923172611","DOIUrl":"10.2174/0115734064244117230923172611","url":null,"abstract":"<p><p>Despite extensive research in the field of drug discovery and development, still there is a need to develop novel molecular entities. Literature reveals a substantial heterocyclic nucleus named, piperazine, which shows an immense therapeutic voyage. For several decades, molecules having the piperazine nucleus have entered the market as a drug exhibiting biological potential. It was known to possess antipsychotic, antihistamine, antianginal, antidepressant, anticancer, antiviral, cardioprotective, and anti-inflammatory activity with a specific basis for structural activity relationship. Thus, it is regarded as a key structural feature in most of the already available therapeutic drugs in the market. Reports also suggest that the extensive utilization of these currently available drugs having a piperazine nucleus shows increasing tolerance significantly day by day. In addition to this, various other factors like solubility, low bioavailability, cost-effectiveness, and imbalance between pharmacokinetics and pharmacodynamics profile limit their utilization. Focusing on that issues, various structural modification studies were performed on the piperazine moiety to develop new derivatives/analogs to overcome the problems associated with available marketed drugs. Thus, this review article aims to gain insight into the number of structural modifications at the N-1 and N-4 positions of the piperazine scaffold. This SAR approach may prove to be the best way to overcome the above-discussed drawbacks and lead to the design of drug molecules with better efficacy and affinity. Hence, there is an urgent need to focus on the structural features of this scaffold which paves further work for deeper exploration and may help medicinal chemists as well as pharmaceutical industries.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"17-29"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41183023","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}

{"title":"Breaking New Ground: The Dawn of Nanopharmaceutics as Antimicrobials.","authors":"Jose Ruben Morones-Ramirez","doi":"10.2174/0115734064267561230925060019","DOIUrl":"10.2174/0115734064267561230925060019","url":null,"abstract":"","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"108-113"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41204644","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}

{"title":"<i>In vitro</i> and <i>In vivo</i> Biological Activity of Two Aryloxy-naphthoquinones in Mice Infected with <i>Trypanosoma cruzi</i> Strains.","authors":"Karina Vázquez, Adriana Moreno-Rodríguez, Luis R Domínguez-Díaz, Jeanluc Bertrand, Cristian O Salas, Gildardo Rivera, Yobana Pérez Cervera, Virgilio Bocanegra-García","doi":"10.2174/0115734064287956240426110450","DOIUrl":"10.2174/0115734064287956240426110450","url":null,"abstract":"<p><strong>Background: </strong>Chagas disease, a condition caused by Trypanosoma cruzi, is an endemic disease in Latin American countries that affects approximately eight million people worldwide. It is a continuing public health problem. As nifurtimox and benznidazole are the two pharmacological treatments currently used to treat it, the present research proposes new therapeutic alternatives. Previous studies conducted on naphthoquinone derivatives have found interesting trypanocidal effects on epimastigotes, with the molecules 2-phenoxy-1,4-naphthoquinone (IC₅₀= 50 nM and SI < 250) and 2-(3-nitrophenoxy)-naphthalene-1,4-dione (IC₅₀= 20 nM and SI=625) presenting the best biological activity..</p><p><strong>Methods: </strong>The present study evaluated the efficacy of <i>in vitro, ex vivo</i> and in vivo models of two aryloxyquinones, 2-phenoxy-1,4-naphthoquinone (1) and 2-(3-nitrophenoxy)-naphthalene-1,4- dione (2), against two Mexican <i>T. cruzi</i> strains in both their epimastigote and blood Trypomastigote stage. Both compounds were evaluated against <i>T. cruzi</i> using a mouse model (CD1) infected with Mexican isolates of <i>T. cruzi</i>, nifurtimox and benznidazole used as control drugs. Finally, the cytotoxicity of the two compounds against the J774.2 mouse macrophage cell line was also determined.</p><p><strong>Results: </strong>The <i>in vitro</i> and <i>in vivo</i> results obtained indicated that both quinones were more active than the reference drugs. Compound 1 presents in vivo activity, showing up to 40% parasite reduction after 8 h of administration, a finding which is 1.25 times more effective than the results obtained using nifurtimox.</p><p><strong>Conclusion: </strong>These are encouraging results for proposing new naphthoquinone derivatives with potential anti-<i>T. cruzi</i> activity.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"938-943"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958401","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}

{"title":"Targeting Diabetes with Azole-derived Medicinal Agents.","authors":"Anuradha Mehra","doi":"10.2174/0115734064289990240524055002","DOIUrl":"10.2174/0115734064289990240524055002","url":null,"abstract":"<p><p>Azoles have long been regarded as an ideal scaffold for the development of numerous innovative therapeutic agents as well as other incredibly adaptable and beneficial chemicals with prospective uses in a variety of fields, including materials, energetics (explosophores), and catalysis (azole organocatalytic arbitration). Azoles exhibit promising pharmacological activities, including antimicrobial, antidiabetic, antiviral, antidepressant, antihistaminic, antitumor, antioxidant, antiallergic, antihelmintic, and antihypertensive activity. According to a database analysis of U.S. FDAapproved medications, 59% of specific medications are connected to small molecules that have heterocycles having nitrogen atoms. The azole moiety has impressive electron abundance. Azoles promptly attach to various receptors as well as enzymes in the physiological environment via distinct specialized interactions, contributing to their anti-diabetic potential. This review encompasses the recent research progress on potent azole-derived antidiabetic agents that can be used as an alternative for the management of type-2 diabetes.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"855-875"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262254","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}

{"title":"Application and Progress of Machine Learning in Pesticide Hazard and Risk Assessment.","authors":"Yunfeng Yang, Junjie Zhong, Songyu Shen, Jiajun Huang, Yihan Hong, Xiaosheng Qu, Qin Chen, Bing Niu","doi":"10.2174/1573406419666230406091759","DOIUrl":"10.2174/1573406419666230406091759","url":null,"abstract":"<p><p>Long-term exposure to pesticides is associated with the incidence of cancer. With the exponential increase in the number of new pesticides being synthesized, it becomes more and more important to evaluate the toxicity of pesticides by means of simulated calculations. Based on existing data, machine learning methods can train and model the predictions of the effects of novel pesticides, which have limited available data. Combined with other technologies, this can aid the synthesis of new pesticides with specific active structures, detect pesticide residues, and identify their tolerable exposure levels. This article mainly discusses support vector machines, linear discriminant analysis, decision trees, partial least squares, and algorithms based on feedforward neural networks in machine learning. It is envisaged that this article will provide scientists and users with a better understanding of machine learning and its application prospects in pesticide toxicity assessment.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"2-16"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9274465","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}

{"title":"Synthesis and Structural Activity Relationship Study of Ursolic Acid Derivatives as Antitubercular Agent.","authors":"Sadhna Vishwakarma, Santosh K Srivastava, Naveen K Khare, Shiwa Chaubey, Vinita Chaturvedi, Priyanka Trivedi, Sana Khan, Feroz Khan","doi":"10.2174/0115734064256660231027042758","DOIUrl":"10.2174/0115734064256660231027042758","url":null,"abstract":"<p><strong>Objective: </strong>The chemical transformation of ursolic acid (UA) into novel C-3 aryl ester derivatives and <i>in vitro</i> and <i>silico</i> assessment of their antitubercular potential.</p><p><strong>Background: </strong>UA is a natural pentacyclic triterpenoid with many pharmacological properties. Semisynthetic UA analogs have demonstrated enhanced anticancer, antimalarial, and antifilarial properties in our previous studies.</p><p><strong>Methods: </strong>The C-30 carboxylic group of previously isolated UA was protected, and various C-3 aryl ester derivatives were semi-synthesized. The agar dilution method was used to evaluate the <i>in vitro</i> antitubercular efficacy of <i>Mycobacterium tuberculosis</i> (Mtb) H₃₇Ra. <i>In silico</i> docking studies of the active derivative were carried out against Mtb targets, catalase peroxidase (PDB: 1SJ2), dihydrofolate reductase (PDB: 4M2X), enoyl-ACP reductase (PDB: 4TRO), and cytochrome bc1 oxidase (PDB: 7E1V).</p><p><strong>Results: </strong>The derivative 3-O-(2-amino,3-methyl benzoic acid)-ethyl ursolate (UA-1H) was the most active among the eight derivatives (MIC1 2.5 μg/mL) against Mtb H₃₇Ra. Also, UA-1H demonstrated significant binding affinity in the range of 10.8-11.4 kcal/mol against the antiTb target proteins, which was far better than the positive control Isoniazid, Ethambutol, and co-crystallized ligand (HEM). Moreover, the predicted hit UA-1H showed no inhibition of Cytochrome P450 2D6 (CYP2D6), suggesting its potential for favorable metabolism in Phase I clinical studies.</p><p><strong>Conclusion: </strong>The ursolic acid derivative UA-1H possesses significant <i>in vitro</i> antitubercular potential with favorable <i>in silico</i> pharmacokinetics. Hence, further <i>in vivo</i> assessments are suggested for UA-1H for its possible development into a secure and efficient antitubercular drug.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"630-645"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72014690","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}

{"title":"Unveiling the ESR1 Conformational Stability and Screening Potent Inhibitors for Breast Cancer Treatment.","authors":"Khushboo Sharma, Umesh Panwar, Maddala Madhavi, Isha Joshi, Ishita Chopra, Lovely Soni, Arshiya Khan, Anushka Bhrdwaj, Abhyuday Singh Parihar, Vineeth Pazharathu Mohan, Leena Prajapati, Rashmi Sharma, Shweta Agrawal, Tajamul Hussain, Anuraj Nayarisseri, Sanjeev Kumar Singh","doi":"10.2174/0115734064256978231024062937","DOIUrl":"10.2174/0115734064256978231024062937","url":null,"abstract":"<p><strong>Background: </strong>The current study recognizes the significance of estrogen receptor alpha (ERα) as a member of the nuclear receptor protein family, which holds a central role in the pathophysiology of breast cancer. ERα serves as a valuable prognostic marker, with its established relevance in predicting disease outcomes and treatment responses.</p><p><strong>Methods: </strong>In this study, computational methods are utilized to search for suitable drug-like compounds that demonstrate analogous ligand binding kinetics to ERα.</p><p><strong>Results: </strong>Docking-based simulation screened out the top 5 compounds - ZINC13377936, NCI35753, ZINC35465238, ZINC14726791, and NCI663569 against the targeted protein. Further, their dynamics studies reveal that the compounds ZINC13377936 and NCI35753 exhibit the highest binding stability and affinity.</p><p><strong>Conclusion: </strong>Anticipating the competitive inhibition of ERα protein expression in breast cancer, we envision that both ZINC13377936 and NCI35753 compounds hold substantial promise as potential therapeutic agents. These candidates warrant thorough consideration for rigorous In vitro and In vivo evaluations within the context of clinical trials. The findings from this current investigation carry significant implications for the advancement of future diagnostic and therapeutic approaches for breast cancer.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"352-368"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71483282","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}

{"title":"Antimicrobial Potential of Polyphenols: An Update on Alternative for Combating Antimicrobial Resistance.","authors":"Alok Sharma, Anurag, Jasleen Kaur, Anuradha Kesharwani, Vipan Kumar Parihar","doi":"10.2174/0115734064277579240328142639","DOIUrl":"10.2174/0115734064277579240328142639","url":null,"abstract":"<p><p>The last decade has encountered an increasing demand for plant-based natural antibiotics. This demand has led to more research-based investigations for natural sources of antimicrobial agents and published reports demonstrating that plant extracts are widely applied in modern medicine, reporting potential activity that may be due to polyphenol compounds. Interestingly, the effects of polyphenols on the sensitivity of bacteria to antibiotics have not been well-studied. Hence, the current review encompasses the prospective application of plant-based phenolic extracts from plants of Indian origin. The emergence of resistance to antimicrobial agents has increased the inefficacy of many antimicrobial drugs. Several strategies have been developed in recent times to overcome this issue. A combination of antimicrobial agents is employed for the failing antibiotics, which restores the desirable effect but may have toxicity-related issues. Phytochemicals such as some polyphenols have demonstrated their potent activity as antimicrobial agents of natural origin to work against resistance issues. These agents alone or in combination with certain antibiotics have been shown to enhance the antimicrobial activity against a spectrum of microbes. However, the information regarding the mechanisms and structure-activity relationships remains elusive. The present review also focuses on the possible mechanisms of natural compounds based on their structure- activity relationships for incorporating polyphenolic compounds in the drug-development processes. Besides this work, polyphenols could reduce drug dosage and may diminish the unhidden or hidden side effects of antibiotics. Pre-clinical findings have provided strong evidence that polyphenolic compounds, individually and in combination with already approved antibiotics, work well against the development of resistance. However, more studies must focus on in vivo results, and clinical research needs to specify the importance of polyphenol-based antibacterials in clinical trials.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"576-596"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852380","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}