Current topics in medicinal chemistry最新文献

{"title":"An Insight into the Structure-Activity Relationship of Benzimidazole and Pyrazole Derivatives as Anticancer Agents.","authors":"Shital M Patil, Piyush Nikalje, Navnath Gavande, Kalyani D Asgaonkar, Vaishnavi Rathod","doi":"10.2174/0115680266343336241021080438","DOIUrl":"https://doi.org/10.2174/0115680266343336241021080438","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer is a leading cause of death worldwide, driving the urgent need for new and effective treatments. Benzimidazole and pyrazole derivatives have gained attention for their potential as anticancer agents due to their diverse biological activities. The development of resistance in cancer cells, toxicity concerns, and inconsistent efficacy across different types of cancer are a few of the challenges. To overcome these challenges, optimisation of these nuclei using the structure-activity relationships is necessary.</p><p><strong>Objective: </strong>This review aimed to examine various benzimidazole, pyrazole, and their hybrid derivatives by focusing on their structure-activity relationships (SAR) as anticancer agents. Results of the most potent and least potent benzimidazole, pyrazole compounds, and their hybrid derivatives published by researchers were compiled.</p><p><strong>Method: </strong>The findings of different researchers working on benzimidazole and pyrazole nuclei were reviewed and analysed for different targets and cell lines. Moreover, substitutions on different positions of pyrazole, benzimidazole, and their hybrid were summarised to derive an optimised pharmacophore.</p><p><strong>Result: </strong>Based on our analysis of existing studies, we anticipate that this review will guide researchers in creating potent pyrazole, benzimidazole, and hybrid derivatives crucial for combating cancer effectively.</p><p><strong>Conclusion: </strong>Structure-Activity Relationship (SAR) studies can help in developing pyrazolebenzimidazole hybrids that are more powerful and selective in targeting specific aspects of cancer.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557375","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 Advances in Amperometric Biosensors for Medical Applications: A Mini-Review.","authors":"Anna S Kharkova, Lubov S Kuznetsova, Kristina D Ivanova, Maria M Gertsen, Vyacheslav A Arlyapov","doi":"10.2174/0115680266323004241015122441","DOIUrl":"https://doi.org/10.2174/0115680266323004241015122441","url":null,"abstract":"<p><p>Amperometric biosensors have emerged as a cutting-edge technology in clinical diagnostics, thanks to their high level of sensitivity, rapid analytical results, compact size, and ability to monitor health parameters non-invasively and continuously using flexible and wearable sensors. This review explores the latest developments in the field of amperometric biosensing for medical applications. It discusses the materials used to construct these sensors and pays particular attention to biosensors designed to measure glucose, lactate, cholesterol, urea, and uric acid levels. The review also addresses the technological limitations and drawbacks of these devices. Furthermore, it presents the current status and identifies future trends in the development of flexible, wearable biosensors capable of providing continuous monitoring of a patient's health status.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544303","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 Advances in Multifaceted Drug Delivery Using Natural Polysaccharides and Polyacrylamide-Based Nanomaterials in Nanoformulation.","authors":"Paromita Dutta Choudhury, Abu Md Ashif Ikbal, Sourav Saha, Rabin Debnath, Bikash Debnath, Loushambam Samananda Singh, Waikhom Somraj Singh","doi":"10.2174/0115680266316522241015143856","DOIUrl":"https://doi.org/10.2174/0115680266316522241015143856","url":null,"abstract":"<p><p>Rapid growth in nanotechnology, also known as 21st-century technology, is occurring in response to the increasing diversity of diseases. The development of safe and effective drug delivery methods to enhance bioavailability is of paramount importance. Researchers have focused on creating safe, cost-effective, and environmentally friendly nanoparticle construction processes. Natural polysaccharides, a type of multifaceted polymer with a wide range of applications and advantages, are particularly well suited for nanoparticle formulations, as they can mitigate the adverse consequences of synthetic nanoparticle formulations and promote sustainability. This review summarizes various sources of natural-based polysaccharides and polyacrylamide-based nanomaterials in nanoparticle preparation. Additionally, it discusses the use of natural polysaccharides in formulations beyond nanotechnology, highlighting their importance in green synthesis and different preparation methods.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544304","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":"Potential Anti-tumor Effects and Apoptosis-Inducing Mechanisms of Saponins: A Review.","authors":"Edvania Emannuelle Pinheiro Santos, Maria Lorena de Oliveira Andrade, Igor José Dos Santos Nascimento, Samuel Paulo Cibulski, Harley da Silva Alves","doi":"10.2174/0115680266315197241015101801","DOIUrl":"https://doi.org/10.2174/0115680266315197241015101801","url":null,"abstract":"<p><p>The search for effective cancer therapies highlights saponins, natural plant-derived compounds, as promising anticancer agents. These compounds induce apoptosis in cancer cells by activating caspases, essential enzymes for cell death. For example, Soyasapogenol B from Glycine max and Astragaloside IV from Astragalus membranaceus effectively trigger apoptosis in cancer cells. Additionally, saponins, such as Compound K from American ginseng and Saikosaponin from Bupleurum falcatum, affect extrinsic and intrinsic pathways, including mitochondrial release of cytochrome C and activation of caspase-9. Ziyuglycoside II also acts on both pathways and activates the ROS/JNK pathway. Understanding these mechanisms provides promising prospects for developing more specific and safer anticancer therapies. The review utilized the ScienceDirect, PubMed, and Google Scholar databases. It was found that original articles and reviews from journals indexed in these sources emphasized the antitumor capabilities of saponins and discussed their role in apoptosis induction and caspase activation. The activation of caspases by saponins in the apoptotic pathway involves two main pathways: the extrinsic pathway is initiated by external signals that activate caspase-8, while the intrinsic pathway starts with internal stimuli, causing the release of cytochrome c and the activation of caspase-9. These pathways both lead to the activation of effector caspases (caspases 3, 6, and 7), culminating in apoptosis, an essential process for maintaining cellular balance and eliminating damaged cells. Identifying saponins in the context of cancer and their mechanisms of action is an ever-evolving field. Future research may lead to more targeted and personalized therapies, highlighting the collaboration between basic and clinical research in this promising area of medicine.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496732","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 Structure-Activity Relationship of COX Inhibitors with Anticancer Effects: A Comprehensive Review.","authors":"Ozlem Akgul, Mustafa Gul, Halise Inci Gul","doi":"10.2174/0115680266333495241011063253","DOIUrl":"https://doi.org/10.2174/0115680266333495241011063253","url":null,"abstract":"<p><p>Cancer is a multifaceted disease with high mortality rates, and current treatments face challenges such as chemoresistance and tumor adaptation. Since Virchow reported the first case of cancer-related chronic inflammation, numerous clinical and epidemiological studies have indicated that around 15-20% of malignant tumors are caused by inflammation. Cyclooxygenase-2 (COX-2), which is the key enzyme in inflammation, has been implicated in tumorigenesis through various mechanisms, including promoting angiogenesis, inhibiting apoptosis, and enhancing the invasiveness of cancer cells. Moreover, COX inhibitors have demonstrated a substantial reduction in death rates associated with esophageal and colon cancer. In this context, targeting COX-2 is an effective strategy for cancer prevention and treatment. This review focuses on the analysis of studies conducted between 2014 and 2024, which evaluate the structure-activity relationship of molecules intended to exhibit cytotoxic activity through COX inhibition. The studies followed both classical and non-classical COX-2 selective drug design strategies. While some focused on the classical approach, utilizing diaryl heterocyclic structures, others explored non-classical designs with a cyclic central scaffold and a linear core. Additionally, several manuscripts employed well-known COX inhibitors, including licofelone, indomethacin, naproxen, tolfenamate, celecoxib, flumizole, and ketoprofen, as starting points for further derivatization and optimization. Cytotoxic activity was evaluated using various cell lines, including MCF- 7, HCT-116, and A549, through assays such as MTT, CellTiter, and MTS. Additionally, studies examined the relationship between COX-2 inhibition and key cancer pathways, including apoptosis and the involvement of enzymes like HDAC, EGFR, and topoisomerase. The majority of studies reported promising cytotoxic activity in COX-2 selective inhibitors. Compounds synthesized with diphenyl heterocyclic scaffolds exhibited enhanced COX-2 selectivity and anticancer efficacy. In particular, derivatives in studies 9, 16, and 24 demonstrated significant activity comparable to standard drugs like celecoxib and doxorubicin. However, only a few studies indicated a weak correlation between COX-2 inhibition and cytotoxicity, suggesting the need for further investigation into other cancer-related mechanisms. This review highlights the potential of COX-2 selective inhibitors in anticancer drug development. The findings support the development of selective COX-2 inhibitors with diverse chemical structures as a promising strategy for cancer therapy.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496730","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":"Envelope Protein in Differential Serodiagnosis of Dengue, Zika, and Chikungunya Viruses: A Systematic Review.","authors":"Amauri Donadon Leal Junior, Fernando Américo Jorge, Franciele Abigail Vilugron Rodrigues-Vendramini, Pollyanna Cristina Vincenzi Conrado, Deborah de Castro Moreira, Rafaela Daleffe Pepino, Isis Regina Grenier Capoci, Patrícia de Souza Bonfim-Mendonça, Luciana Dias Ghiraldi Lopes, Dennis Armando Bertolini, Izabel Galhardo Demarchi, Jorge Juarez Vieira Teixeira, Érika Seki Kioshima","doi":"10.2174/0115680266348828241008214528","DOIUrl":"https://doi.org/10.2174/0115680266348828241008214528","url":null,"abstract":"<p><strong>Objectives: </strong>This systematic review was conducted to evaluate the applicability of the envelope (E) protein in the diagnosis of arboviruses.</p><p><strong>Methods: </strong>This review was performed in accordance with the PRISMA statement. Five databases were explored (PubMed, Web of Science, Scopus, EMBASE, and IEDB). The inclusion and exclusion criteria were applied to study eligibility. After data extraction, the risk of bias and evidence certainty were evaluated according to QUADAS and GRADE assessments, respectively.</p><p><strong>Results: </strong>Eleven studies were included. A total of 11 studies were included in the review. ELISA was the most frequently utilized technique, with two studies employing it for antigen detection and nine for antibodies. The E protein was used as a whole protein, heterologous protein, and peptides. The diagnostic metrics were enhanced by optimizations on techniques, such as antibody capture, competitors, and nanosensors. Monoclonal antibodies showed improved specificity, including in coinfected samples. Seven studies demonstrated a minimal risk of bias, and the evidence certainty was considered moderate for dengue diagnosis.</p><p><strong>Conclusions: </strong>The E protein was successfully employed in different immunological assays with large-scale strategies, enhancing the applicability potential for differential arboviruses' diagnosis. Furthermore, both the antigen design and the implementation of innovative methodologies will have a substantial impact on the quality of the new tests. The PROSPERO protocol related to this work: CRD42021265243.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460124","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":"The Anti-Leukemic Activities of Campesterol and Α-Tocopherol Against BCL-2 Target through Computational Drug Design Approaches.","authors":"Oluwayemisi Titobioluwa Agbeniyi, Neeraj Kumar, Najwa Ahmad Kuthi, Yinka Okunola, Tomilola Victor Akingbade, Christopher Busayo Olowosoke, Idayat Oyinkansola Kehinde, Omoboyede Victor, Haruna Isiyaku Umar, Rahul Dev Bairagi, Yousef A Bin Jardan, Mohammed Bourhia","doi":"10.2174/0115680266316570240926081647","DOIUrl":"https://doi.org/10.2174/0115680266316570240926081647","url":null,"abstract":"<p><strong>Introduction: </strong>Heterogeneous Acute Myeloid Leukemia (AML) causes substantial worldwide morbidity and death. AML is characterized by excessive proliferation of immature myeloid cells in the bone marrow and impaired apoptotic regulator expression.</p><p><strong>Method: </strong>B-Cell Lymphoma 2 (BCL-2), an anti-apoptotic protein overexpressed in AML, promotes leukemic cell survival and chemoresistance. Thus, reducing BCL-2 may treat AML. Anticancer activities are found in Aloe barbadensis Miller (Aloe vera). Thus, this work used molecular modeling to assess Aloe vera bioactive chemicals as BCL-2 inhibitors. Molecular docking simulation showed that all identified Aloe vera phytocompounds have strong BCL-2 binding affinities (-6.7 to -8.7 kcal/mol).</p><p><strong>Result: </strong>Campesterol and α-tocopherol were identified as promising compounds for BCL-2 inhibitor research based on their drug-likeness, pharmacokinetics, and toxicity profiles. The stability and conformational of the BCL-2-compound complexes showed that the compounds were stable in BCL-2's binding pocket.</p><p><strong>Conclusion: </strong>Campesterol and α-tocopherol are promising BCL-2 inhibitors that might become effective anti-leukemic therapies with additional in vitro and in vivo research.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460126","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":"Non-fused Pyrimidine Derivatives as Potential Pharmacological Entities: A Review.","authors":"Khyati L Bharti, Parnas S Parmar, Bhavesh P Rathod, Sharmil N Anjirwala, Saurabh K Patel","doi":"10.2174/0115680266317088240924205745","DOIUrl":"https://doi.org/10.2174/0115680266317088240924205745","url":null,"abstract":"<p><p>Non-fused pyrimidine scaffold is a significant component for designing new drugs. The review emphasizes the pharmacological importance of non-fused pyrimidine-containing moieties based on the broad spectrum of activities such as antiprotozoal, antibacterial, antimycobacterial, anticancer, anti-inflammatory activity, and CNS depressant. Pyrimidine derivatives are fascinating entities that display biological activities for the treatment of cancer. It also highlights the tendency of non-fused pyrimidine derivatives to suppress cell growth by obstructing the activity of VCP, CDK-2, EGFR, ATR, EphB4 & EphA2, PDGF as well as inhibitory action towards different cell lines such as MCF-7, HeLa, NCI/ADR-RES, NCIH23, HOP-92, HCT-116, OV-3, MOLT-4, PC-3, MDA-MB-231, MALME-3M, K562 and Bcr-Abl. The review details the importance of morpholine, piperidine, and pyrrolidine ring substitutions on pyrimidine moiety as well as the role of H-bonding and amino linkage along with antibacterial activity due to the presence of pleuromutilin and tetrazole molecules. Researchers were motivated to develop and enhance the non-fused pyrimidine scaffold to uncover novel medicines by reading this review article.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460125","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":"Computational Studies in Dermo-cosmetics: In silico Discovery of Therapeutic Agents Targeting a Variety of Proteins for Skin Diseases.","authors":"Lamiae El Bouamri, Mohammed Bouachrine, Samir Chtita","doi":"10.2174/0115680266337405240926114604","DOIUrl":"https://doi.org/10.2174/0115680266337405240926114604","url":null,"abstract":"<p><p>Healthy skin is essential for balanced health. Currently, skin diseases are considered a major global health issue, impacting individuals of all ages. Skin conditions can vary broadly, ranging from common issues like acne and eczema to more serious diseases such as psoriasis, melanoma, and other types of skin cancer. In recent years, computational methods have appeared as powerful tools for explaining the lurking mechanisms of skin diseases and the advancement of the discovery regarding updated therapeutics. This review spotlights the notable researches that have been performed in using computational approaches such as virtual screening, molecular modelling, and molecular dynamics simulations to discover potential treatments for dermatological conditions such as eczema, psoriasis, acne vulgaris, skin cancer, and tyrosinase-related disorders. Moreover, using in silico methods, researchers have explored the molecular interactions between cosmetic actives and skin targets, providing insights into the binding affinities, stability, and efficacy of these compounds. This computational exploration allows the identification of potential off-target effects and toxicity profiles, ensuring that only the most promising candidates proceed to clinical testing. In addition, the use of molecular dynamics simulations helps to understand conformational changes and interaction dynamics over time, further refining the selection of effective cosmetic actives. Overall, the integration of computational chemistry into dermo-cosmetic research has immense potential to accelerate the discovery and development of innovative treatments to improve skin health and address dermatological concerns.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460123","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":"Identification of Novel Tyrosinase Inhibitors with Nanomolar Potency Using Virtual Screening Approaches.","authors":"Guohong Liu, Shihao Liu, Xiaofang Li, Tegexibaiyin Wang","doi":"10.2174/0115680266333084240918051716","DOIUrl":"https://doi.org/10.2174/0115680266333084240918051716","url":null,"abstract":"<p><strong>Introduction: </strong>Hyperpigmentation disorders are caused by excess production of the pigment melanin, catalyzed by the enzyme tyrosinase. Novel tyrosinase inhibitors are needed as therapeutic agents to treat these conditions.</p><p><strong>Method: </strong>To discover new inhibitors, we performed a virtual screening of the ZINC20 library containing 1.4 billion compounds. An initial filter for drug-likeness, ADMET properties, and synthetic accessibility reduced the library to 10,217 hits. Quantitative structure-activity relationship (QSAR) modeling of this subset predicted nanomolar inhibitory potency for several chemical scaffolds. Comparative molecular docking studies and rigorous binding energy calculations further prioritized four cysteine-containing dipeptide compounds based on predicted strong binding affinity and mode to tyrosinase.</p><p><strong>Results: </strong>Microsecond-long molecular dynamics simulations provided additional atomistic insights into the stability of inhibitor-enzyme binding interactions. This integrated computational workflow effectively sampled an extremely large chemical space to discover four novel tyrosinase inhibitors with half-maximal inhibitory concentration values below 10 nM.</p><p><strong>Conclusion: </strong>Overall, this demonstrates the power of virtual screening and multi-faceted computational techniques to accelerate the discovery of potent bioactive ligands from massive compound libraries by efficiently sampling chemical space.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364766","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}