Medicinal Chemistry最新文献

{"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":"A Review on the Development of Novel Heterocycles as α-Glucosidase Inhibitors for the Treatment of Type-2 Diabetes Mellitus.","authors":"Prexa Patel, Drashti Shah, Tushar Bambharoliya, Vidhi Patel, Mehul Patel, Dharti Patel, Vashisth Bhavsar, Shantilal Padhiyar, Bhavesh Patel, Anjali Mahavar, Riddhisiddhi Patel, Ashish Patel","doi":"10.2174/0115734064264591231031065639","DOIUrl":"10.2174/0115734064264591231031065639","url":null,"abstract":"<p><p>One of the most effective therapeutic decencies in the treatment of Type 2 Diabetes Mellitus is the inhibition of α-glucosidase enzyme, which is present at the brush border of the intestine and plays an important role in carbohydrate digestion to form mono-, di-, and polysaccharides. Acarbose, Voglibose, Miglitol, and Erniglitate have been well-known α-glucosidase inhibitors in science since 1990. However, the long synthetic route and side effects of these inhibitors forced the researchers to move their focus to innovate simple and small heterocyclic scaffolds that work as excellent α-glucosidase inhibitors. Moreover, they are also effective against the postprandial hyperglycemic condition in Type 2 Diabetes Mellitus. In this aspect, this review summarizes recent progress in the discovery and development of heterocyclic molecules that have been appraised to show outstanding inhibition of α-glucosidase to yield positive effects against diabetes.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"503-536"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139564369","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":"Trends in the Synthesis of Antimicrobial Derivatives by using the Gewald, Strecker, and Groebke-Blackburn-Bienaymé (GBB) Reactions.","authors":"Kaushal Naithani, Subhendu Bhowmik","doi":"10.2174/0115734064282699240315042428","DOIUrl":"10.2174/0115734064282699240315042428","url":null,"abstract":"<p><strong>Background: </strong>Multicomponent reactions are highly useful in synthesizing natural products and bioactive molecules. Out of several MCRs, although utilized widely, some remain neglected in review articles. The Gewald and Groebke-Blackburn-Bienaymé (GBB) reactions are two such reactions. This comprehensive review assimilates applications of Gewald and Groebke-Blackburn- Bienayme reactions in synthesizing novel antimicrobial agents. It presents the antimicrobial properties of the synthesized molecules, providing an overview of their potential druggability.</p><p><strong>Objective: </strong>Developing novel antimicrobial agents is the need of the hour. Toward this objective, the scientific community is developing new methods for constructing novel architectures with potential antimicrobial properties. This review will showcase the usefulness of the Gewald, Strecker, and Groebke-Blackburn-Bienaymé (GBB) reactions in synthesizing antimicrobial molecules.</p><p><strong>Methods: </strong>The articles are searched by using the Sci-finder search tool and summarize the chemistry of their synthesis and antimicrobial evaluation of the molecules.</p><p><strong>Results: </strong>This review focuses on synthesizing antimicrobial molecules using the Gewald, Strecker, and Groebke-Blackburn-Bienaymé (GBB) reactions. The antimicrobial activities of the synthesized molecules are also summarized in tables.</p><p><strong>Conclusion: </strong>This review will briefly overview the application of the Gewald, Strecker, and Groebke- Blackburn-Bienaymé (GBB) reactions in synthesizing novel antimicrobial molecules. It contains several molecules with promising activity against resistant and non-resistant microbial strains. These promising molecules could be studied further to develop novel antibiotics.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"663-688"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207232","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}

{"title":"Synthetic Protocols, Structural Activity Relationship, and Biological Activity of Piperazine and its Derivatives.","authors":"Md Faizan, Rajnish Kumar, Avijit Mazumder, Salahuddin, Neelima Kukreti, Arvind Kumar, M V N L Chaitanya","doi":"10.2174/0115734064304396240415110015","DOIUrl":"10.2174/0115734064304396240415110015","url":null,"abstract":"<p><p>The versatile basic structure of piperazine allows for the development and production of newer bioactive molecules that can be used to treat a wide range of diseases. Piperazine derivatives are unique and can easily be modified for the desired pharmacological activity. The two opposing nitrogen atoms in a six-membered piperazine ring offer a large polar surface area, relative structural rigidity, and more acceptors and donors of hydrogen bonds. These properties frequently result in greater water solubility, oral bioavailability, and ADME characteristics, as well as improved target affinity and specificity. Various synthetic protocols have been reported for piperazine and its derivatives. In this review, we focused on recently published synthetic protocols for the synthesis of the piperazine and its derivatives. The structure-activity relationship concerning different biological activities of various piperazine-containing drugs was also highlighted to provide a good understanding to researchers for future research on piperazines.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"753-780"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140866606","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}