Current topics in medicinal chemistry最新文献

{"title":"Recent Advances in the Treatment and Management of Alzheimer’s Disease: A Precision Medicine Perspective","authors":"Deepali Shukla, Anjali Suryavanshi, Sanjay Kumar Bharti, Vivek Asati, Debarshi Kar Mahapatra","doi":"10.2174/0115680266299847240328045737","DOIUrl":"https://doi.org/10.2174/0115680266299847240328045737","url":null,"abstract":": About 60% to 70% of people with dementia have Alzheimer's Disease (AD), a neuro-degenerative illness. One reason for this disorder is the misfolding of naturally occurring proteins in the human brain, specifically β-amyloid (Aβ) and tau. Certain diagnostic imaging techniques, such as amyloid PET imaging, tau PET imaging, Magnetic Resonance Imaging (MRI), Comput-erized Tomography (CT), and others, can detect biomarkers in blood, plasma, and cerebral spinal fluids, like an increased level of β-amyloid, plaques, and tangles. In order to create new pharma-cotherapeutics for Alzheimer's disease, researchers must have a thorough and detailed knowledge of amyloid beta misfolding and other related aspects. Dolopezil, rivastigmine, galantamine, and other acetylcholinesterase inhibitors are among the medications now used to treat Alzheimer's disease. Another medication that can temporarily alleviate dementia symptoms is memantine, which blocks the N-methyl-D-aspartate (NMDA) receptor. However, it is not able to halt or re-verse the progression of the disease. Medication now on the market can only halt its advance-ment, not reverse it. Interventions to alleviate behavioral and psychological symptoms, exhibit an-ti-neuroinflammation and anti-tau effects, induce neurotransmitter alteration and cognitive en-hancement, and provide other targets have recently been developed. For some Alzheimer's pa-tients, the FDA-approved monoclonal antibody, aducanumab, is an option; for others, phase 3 clinical studies are underway for drugs, like lecanemab and donanemab, which have demonstrat-ed potential in eliminating amyloid protein. However, additional study is required to identify and address these limitations in order to reduce the likelihood of side effects and maximize the thera-peutic efficacy.","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":"8 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591373","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":"Phytochemicals for Cancer Treatment: An Update on Plant-Derived Anti-Cancer Compounds and their Mechanisms of Action.","authors":"Sana Ullah, Tariq Khan, Taimoor Khan, Muhammad Ali, Abdul Khaliq Jan, Zabta Khan Shinwari, Ajmal Khan, Mohamed Al-Farsi, Muhammad Waqas","doi":"10.2174/0115680266268185240320085619","DOIUrl":"https://doi.org/10.2174/0115680266268185240320085619","url":null,"abstract":"<p><p>Cancer remains one of the major causes of morbidity and mortality worldwide. Scientists from different fields are working to devise an efficient treatment strategy in order to reduce the global burden of cancer. Commonly used treatment approaches for cancer treatment include chemotherapy, immunotherapy, photodynamic therapy, radiation, surgery, etc. These treatment procedures have several pitfalls, such as toxicity, limited bioavailability, rapid elimination, poor specificity, and high cost. On the other side, plant-derived anticancer compounds exhibit several advantages and can overcome these shortcomings. Plant-based anticancer compounds are safer, potent, easily available, and comparatively cost-effective. The current review discusses pure plant- based compounds that are used as a therapeutic remedy for anticancer application. The proposed mechanisms of action, through which these compounds inhibit cancer cell growth, tumor growth, angiogenesis, instigate apoptosis, cytotoxicity, mitochondrial membrane degradation, and reduce cell viability as well as cell cycle progression, are also reviewed. These naturally occurring compounds exhibit great therapeutic potential and could be used as candidate drugs in clinical applications.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140317985","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":"Green Synthesis of Biorelevant Scaffolds through Organocatalytic/ Enzymatic Dynamic Kinetic Resolution.","authors":"Hélène Pellissier","doi":"10.2174/0115680266294434240322043536","DOIUrl":"https://doi.org/10.2174/0115680266294434240322043536","url":null,"abstract":"<p><p>This review highlights major developments in the application of green organocatalytic and enzymatic dynamic kinetic resolutions (DKRs) in the total synthesis of biorelevant scaffolds. It illustrates the diversity of useful bioactive products and intermediates that can be synthesized under greener and more economic conditions through the combination of the powerful concept of DKR, which allows the resolution of racemic compounds with up to 100% yield, with either asymmetric organocatalysis or enzymatic catalysis, avoiding the use of toxic and expensive metals. With the need for more ecologic synthetic technologies, this field will undoubtedly expand its scope in the future with the employment of other organocatalysts/enzymes to even more types of transformations, thus allowing powerful greener and more economic strategies to reach other biologically important molecules.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305158","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":"Actinomycetes - The Repertoire of Diverse Bioactive Chemical Molecules: From Structures to Antibiotics.","authors":"Ishfaq Ahmad Baba, Zubair Ahmad Wani, Shazia Ali, Zahoor Ahmad, Mohamad Mosa Mubarak","doi":"10.2174/0115680266282919240224130345","DOIUrl":"https://doi.org/10.2174/0115680266282919240224130345","url":null,"abstract":"<p><p>The urgent need for novel antibiotics in the face of escalating global antimicrobial resistance necessitates innovative approaches to identify bioactive compounds. Actinomycetes, renowned for their prolific production of antimicrobial agents, stand as a cornerstone in this pursuit. Their diverse metabolites exhibit multifaceted bioactivities, including potent antituberculosis, anticancer, immunomodulatory, immuno-protective, antidiabetic, etc. Though terrestrial sources have been exploited significantly, contemporary developments in the field of antimicrobial drug discovery have put marine actinomycetes in a prominent light as a promising and relatively unexplored source of novel bioactive molecules. This is further boosted by post-genomic era advances like bioinformatics-based secretome analysis and reverse engineering that have totally revitalized actinomycetes antibiotic research. This review highlights actinomycetes-based chemically diverse scaffolds and clinically validated antibiotics along with the enduring significance of actinomycetes from untouched ecosystems, especially with recent advanced techniques in the quest for next-generation antimicrobials.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131000","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":"Recent Trends in Nanomaterial Based Electrochemical Sensors for Drug Detection: Considering Green Assessment","authors":"Tugba Ozer, Charles S. Henry","doi":"10.2174/0115680266286981240207053402","DOIUrl":"https://doi.org/10.2174/0115680266286981240207053402","url":null,"abstract":": An individual’s therapeutic drug exposure level is directly linked to corresponding clinical effects. Rapid, sensitive, inexpensive, portable and reliable devices are needed for diagnosis related to drug exposure, treatment, and prognosis of diseases. Electrochemical sensors are useful for drug monitoring due to their high sensitivity and fast response time. Also, they can be combined with portable signal read-out devices for point-of-care applications. In recent years, nanomaterials such as carbon-based, carbon-metal nanocomposites, noble nanomaterials have been widely used to modify electrode surfaces due to their outstanding features including catalytic abilities, conductivity, chemical stability, biocompatibility for development of electrochemical sensors. This review paper presents the most recent advances about nanomaterials-based electrochemical sensors including the use of green assessment approach for detection of drugs including anticancer, antiviral, anti-inflammatory, and antibiotics covering the period from 2019 to 2023. The sensor characteristics such as analyte interactions, fabrication, sensitivity, and selectivity are also discussed. In addition, the current challenges and potential future directions of the field are highlighted.","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":"289 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139955524","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":"Repurposing of Plant-based Antiviral Molecules for the Treatment of COVID-19","authors":"Jabeena Khazir, Rakesh Kr Thakur, Sajad Ahmed, Manzoor Hussain, Sumit G. Gandhi, Sadhana Babbar, Shabir Ahmad Mir, Nusrat Shafi, Libert Brice Tonfack, Vijay Rani Rajpal, Tariq Maqbool, Bilal Ahmad Mir, Latif Ahmad Peer","doi":"10.2174/0115680266276749240206101847","DOIUrl":"https://doi.org/10.2174/0115680266276749240206101847","url":null,"abstract":": COVID-19, stemming from SARS-CoV-2, poses a formidable threat to global healthcare, with a staggering 77 million confirmed cases and 690,067 deaths recorded till Decem-ber 24, 2023. Given the absence of specific drugs for this viral infection, the exploration of novel antiviral compounds becomes imperative. High-throughput technologies are actively engaged in drug discovery, and there is a parallel effort to repurpose plant-based molecules with established antiviral properties. In this context, the review meticulously delves into the potential of plant-based folk remedies and existing molecules. These substances have showcased substantial viral inhibition in diverse in vivo, in silico, and in vitro studies, particularly against critical viral protein targets, including SARS-CoV-2. The findings position these plant-based molecules as promising antiviral drug candidates for the swift advancement of treatments for COVID-19. It is noteworthy that the inherent attributes of these plant-based molecules, such as their natural origin, potency, safety, and cost-effectiveness, contribute to their appeal as lead candidates. The review advocates for further exploration through comprehensive in vivo studies conducted on animal models, em-phasizing the potential of plant-based compounds to help in the ongoing quest to develop effec-tive antivirals against COVID-19.","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":"33 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139955523","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":"Gallic Acid Derived 1, 2-Diarylindole as a Potential Antifungal Agent against Candida Strain.","authors":"Alka Kurmi, Akash Pratap Singh, Yashveer Gautam, Nandan Singh, Alok Tripathi, Arvind Singh Negi, Hemant K Gautam, Anirban Pal, Dharmendra Saikia","doi":"10.2174/0115680266278892240102045630","DOIUrl":"https://doi.org/10.2174/0115680266278892240102045630","url":null,"abstract":"<p><strong>Background: </strong>In recent decades, Candida albicans has become a serious issue for public health. The worldwide rapid rise in drug resistance to conventional therapies is the main contributing reason. Moreover, because of their potent activity at low concentrations and apparent lack of toxicity, compounds originating from plants are used in therapeutic treatments because of their potent activity at low concentrations and apparent lack of toxicity. Particularly in immunocompromised people, Candida species can result in a wide range of ailments.</p><p><strong>Objectives: </strong>Present manuscript describes antifungal activity of an indole derivative 1-(4-((5- methoxy-2-(3,4,5-trimethoxyphenyl)-1H-indol-1-yl) methyl) phenoxy)-N,N-dimethylethan-1- amine (7, 100DL-6) by using an in-silico and in-vitro anti-candidal activity against two Candida strains; Candida kefyr-DS-02 (ATCC-204093) and Candida albicans (AI-clinical isolate, AIIMS- Delhi).</p><p><strong>Methods: </strong>The synthetic strategy for the preparation of indole derivatives was modified through Fischer indole reaction. Antifungal activity of an indole derivative 1-(4-((5-methoxy-2-(3,4,5- trimethoxyphenyl)-1H-indol-1-yl) methyl) phenoxy)-N,N-dimethylethan-1-amine (7, 100DL-6) was done by using an in-silico and in-vitro anti-candidal activity against two Candida strains; Candida kefyr-DS-02 (ATCC-204093) and Candida albicans (AI-clinical isolate, AIIMS-Delhi). Compound 100DL-6 efficacy was determined by Combination synergy study, ergosterol binding assay, MTT toxicity study and Mutagenicity.</p><p><strong>Results: </strong>Compound 100DL-6 was obtained in 65% yield on desired motifs. Docking scores found were 100DL-6 (-8.7 kcal/mol) and Fluconazole (-7.6 kcal/mol). Further, RMSD were shown for 100DL6 (0.26 ± 0.23 nm) and fluconazole (1.2 ± 0.62 nm). Indole derivative 100DL-6 was active against the tested fungal pathogens and the total zone of inhibition was measured between 13-14 mm in diameter and MIC values between 31.25 μg/mL to 250 μg/mL and MFC values between 62.5 μg/mL to 500 μg/mL. In checkerboard assay synergistic mode of interaction of 100DL-6 with known antifungal drugs was observed. In the presence of ergosterol 100DL-6 and standard drug (s) increased their MIC values, demonstrating a considerable affinity for ergosterol. Compound 100DL-6 was considered to be less-cytotoxic to the cells as determined by MTT assay. Lead compound 100DL-6 was found to be non-mutagenic.</p><p><strong>Conclusion: </strong>In the present study, 100DL6 (indole derivatives) significantly abrupted the ergosterol biosynthetic pathway and showed moderate anti-candidal effects. These studies suggest that 100DL6 significantly enhances antifungal effect of clinical drug fluconazole synergistically and may be considered as in clinical trial prior to some extensive in-vivo validations.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140317983","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 New Advanced Approach: Design and Screening of Affinity Peptide Ligands Using Computer Simulation Techniques","authors":"Zheng Wei, Meilun Chen, Xiaoling Lu, Yijie Liu, Guangnan Peng, Jie Yang, Chunhua Tang, Peng Yu","doi":"10.2174/0115680266281358240206112605","DOIUrl":"https://doi.org/10.2174/0115680266281358240206112605","url":null,"abstract":"Peptides acquire target affinity based on the combination of residues in their sequences and the conformation formed by their flexible folding, an ability that makes them very attractive biomaterials in therapeutic, diagnostic, and assay fields. With the development of computer technology, computer-aided design and screening of affinity peptides has become a more efficient and faster method. This review summarizes successful cases of computer-aided design and screening of affinity peptide ligands in recent years and lists the computer programs and online servers used in the process. In particular, the characteristics of different design and screening methods are summarized and categorized to help researchers choose between different methods. In addition, experimentally validated sequences are listed, and their applications are described, providing directions for the future development and application of computational peptide screening and design.","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":"115 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140100238","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":"Molecular Biomarkers in Cholangiocarcinoma: Focus on Bile","authors":"Andrey D. Dolbnya, Igor A. Popov, Stanislav I. Pekov","doi":"10.2174/0115680266290367240130054142","DOIUrl":"https://doi.org/10.2174/0115680266290367240130054142","url":null,"abstract":": Hepatobiliary system cancers have demonstrated an increasing incidence rate in the past years. Without the presence of early symptoms, the majority of such cancers manifest with a set of similar symptoms, such as cholestasis resulting in posthepatic icterus. Differential diagnosis of hepatobiliary cancers is required for the therapy selection, however, the similarity of the symptoms complicates diagnostics. Thus, the search for molecular markers is of high interest for such patients. Cholangiocarcinoma (CCA) is characterized by a poor prognosis due to a low resectability rate, which occurs because this disease is frequently beyond the limits of surgical therapy at the time of diagnosis. The CCA is diagnosed by the combination of clinical/biochemical features, radiological methods, and non-specific serum tumor biomarkers, although invasive examination is still needed. The main disadvantage is limited specificity and sensitivity, which complicates early diagnostics. Therefore, prognostic and predictive biomarkers are still lacking and urgently needed for early diagnosis. In contrast to serum, bile is more accessible to identify biliary disease due to its simpler composition. Moreover, bile can contain higher concentrations of tumor biomarkers due to its direct contact with the tumor. It is known that the composition of the main bile component - bile acids, may vary during different diseases of the biliary tract. This review summarizes the recent developments in the current research on the diagnostic biomarkers for CCA in serum and bile and provides an overview of the methods of bile acids analysis.","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":"218 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139668440","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":"Deciphering Tuberculous Meningitis: From Clinical Challenges to Novel Models and Pathogenic Pathways.","authors":"Mohamad Mosa Mubarak, Shahnawaz Majeed, Hadiya Amin Kantroo, Zubair Ahmad Wani, Abbass Malik, Zahoor Ahmad, Ishfaq Ahmad Baba","doi":"10.2174/0115680266282277240122073451","DOIUrl":"https://doi.org/10.2174/0115680266282277240122073451","url":null,"abstract":"<p><p>During and after the COVID-19 pandemic,Tuberculosis (TB) has reestablished with higher figures due to interruptions in the Directly Observed Treatment Short course (DOTS) despite underreporting. The rising consequences would have extended to extra-pulmonary forms of TB as well, including Tuberculous Meningitis (TBM). Considering the fact that TBM is the most dangerous and worst form of TB, we found the need to scan the literature to highlight various aspects of TBM. Epidemiology of TBM is proportionally less frightening, but the consequent mortalities and morbidities are more alarming than pulmonary TB. Here, we address critical research gaps in Tuberculous Meningitis that warrant further investigations. The highlighted aspects encompass a comprehensive understanding of TBM's clinical presentation and improved diagnostic tools for timely detection, the exploration of innovative chemotherapies and surgical interventions, the unraveling of the role of the blood-brain barrier in disease onset, investigating of the contributions of various brain cells to TBM development, deciphering the complex inflammatory response, exploring the involvement of Matrix Metalloproteinases in tissue damage, delving into host-pathogen genetics influencing susceptibility, utilizing robust in-vivo and in-vitro models for mechanistic insights, and more importantly between TBM and SARS-COVID-19 are discussed. Addressing these gaps will substantially advance our understanding of TBM's complex pathogenesis, contributing to more effective diagnostic, therapeutic, and preventive strategies against this debilitating disease.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139574861","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}